Medifocus Dec 2012

Chronic Kidney Disease - Role of Physician in
The Management And Prevention

Dr (Prof) Sham Sunder and Dr Venkataramanan K
Chronic kidney diseases have become a CKD is a disease which is highly under
major cause of global morbidity and diagnosed and under treated.
mortality both developed and in Establishing preventive program is
developing countries. CKD is a problem required to reduce burden of CKD.
of epidemic proportions in India, and Since, CKD is one of the most
with an increasing diabetes, devastating, expensive disease and not
hypertension burden, and growing an uncommon life-threatening condition
elderly population. Under recognition of requiring care by nephrologists, is a
common condition with a range of
earlier stages of CKD and of risk factors
severity meriting attention by general
for CKD, may partially explain the rising
physician, and demanding strategies for
prevalence of treated ESRD. Increasing
prevention, early detection, and
evidence accumulated in the past
management.
decades indicates that earlier stages of
CKD can be detected through laboratory Definition of CKD
testing, and that therapeutic CKD is defined by the presence of
interventions implemented early in the kidney damage or decreased kidney
course of CKD are effective in slowing or function for three or more months,
preventing the progression toward ESRD irrespective of the cause. The persistence
and its associated complications of the damage or decreased function for
Screening, early diagnosis and early at least three months is necessary to
referral of high risk patient by physicians distinguish CKD from acute kidney
and subspecialties is the key to reduce disease. Kidney damage refers to
CKD burden. pathologic abnormalities, whether
established via renal biopsy or imaging
Introduction studies, or inferred from markers such as
In 21st century CKD is global pandemic, urinary sediment abnormalities or
evolved as major public health issue. CKD increased rates of urinary albumin
is major silent killer and is highly under excretion.
diagnosed and under treated. The
Table 1. Formula for EGFR calculator
number of cases of end-stage renal
disease (ESRD) in India is increasing due 1. Equation from the Modification of
to risk factors such as diabetes1. It is Diet in Renal Disease study*
estimated that about 500 millions are Estimated GFR (mL/min per 1.73 m2) =
known patient of CKD globally. 1.86 x (PCr)–1.154 x (age)–0. 203
Dr (Prof) Sham Sunder CKD is irreversible progressive disease Multiply by 0.742 for women,Multiply
Dr Venkataramanan K * ultimately leading to ESRD and also by 1.21 for African Americans
Head of department premature CAD. Prevalence and 2. Cockcroft-Gault equation
DM Nephrology* incidence of CKD is increasing fast. Every
Estimated creatinine clearance
Department of Nephrology third diabetic and every fifth
(mL/min)
Dr Ram Manohar Lohia hypertensive is case of CKD. Mean age
Hospital and PGIMER = (140–age) x body weight (kg)/72 x
of patient entering ESRD in our country is
New Delhi
PCr (mg/dL)
42 years as compare to 62 years in
Multiply by 0.85 for women
Western countries.
Vol. 11, Issue 4, October 2012

Table 2. Revised CKD classification based upon Decreased kidney function refers to a decreased
GFR and albuminuria.2 glomerular filtration rate (GFR), which is usually estimated
(eGFR) using Serum Creatinine Concentration (PCr), Age,
GFR stages GFR
(mL/min/1.73 m2) Sex, Race, and Body Weight.
G1 >90 Normal or high
G2 60-89 Mildly decreased Prevention of Chronic Kidney Disease
Prevention of CKD mainly involves the Screening for
G3a 45-59 Mildly to moderately
decreased chronic kidney disease and preventing or slowing the
G3b 30-44 Moderately to severely progression of renal disease.
decreased
G4 15-29 Severely decreased Screening for Chronic Kidney Disease - The presence of
G5 <15 Kidney failure (add D if the following risk factors for CKD should provoke formal
treated by dialysis) testing for CKD:
Albuminuria AER (mg/d) Terms · History of diabetes, cardiovascular disease,
stages hypertension, hyperlipidemia, obesity, metabolic
A1 <30 Normal to high normal syndrome, smoking, HIV or hepatitis C virus infection,
(may be subdivided for and malignancy
risk prediction)
· Family history of kidney disease, treatment with
A2 30-300 High (predict
microalbuminuria) potentially nephrotoxic drugs, and all patients over
age 60 years.
A3 >300 Very high (may be
subdivided into nephrotic
and non-nephrotic for NKF-K/DOQI guidelines proposed an algorithm for the
differential diagnosis, evaluation of proteinuria Fig:1
management and risk
prediction)
Evaluation for proteinuria
Not at risk at risk
Standard dipstick Albumin specific dipstick
>1+ Negative / trace Negative positive
Total protein / creatinine ratio Albumin / creatinine ratio
>200 mg/g <200mg/g <30 mg/g >30mg/g
Recheck at periodic health evaluation
Diagnosis evaluation
Treatment Consultation
Fig:1

Methods of screening - All patients who have risk factors mg/day or more), the blood pressure should be
for CKD should be screened with both a urine test for lowered to less than 130/80 mmHg.
albumin in a first morning or a random "spot" urine sample · In patients with nonproteinuric CKD (less than 500mg
(Fig 1) and a blood test for creatinine to estimate GFR. /day), the blood pressure should be lowered to less
than 140/90 mmHg in all patients, and to less than
Slowing the Rate of Progression of Renal Disease 130 to 135 mmHg systolic if it can be achieved
Therapy to slow the rate of progression in patients with without producing significant side effects.
chronic kidney disease (CKD) includes the treatment of the
underlying disease, attaining the blood pressure goal 2. Control of Blood Glucose:
and, in patients with proteinuric disease, attaining the Diabetic nephropathy is now the leading cause of CKD
proteinuria goal. requiring renal replacement therapy (>40%). Excellent
glycemic control reduces the risk of kidney disease and its
1) Control of Blood Pressure progression in both type 1 and type 2 diabetes mellitus. It
Treating hypertension can both slow the progression of is recommended that plasma values for preprandial
proteinuric CKD and reduce the rate of cardiovascular glucose be kept in the 90–130 mg/dL range and
complications. The desired degree of blood pressure hemoglobin A1C should be < 7%. Renal degradation of
control can usually be safely achieved with combined administered insulin will decline, so that less insulin may be
therapy which usually begins with an ACE inhibitor or required for glycemic control drugs.
angiotensin II receptor blocker (by monitoring
hyperkalemia) and a diuretic. 3. Control of proteinuria:
Increased urinary protein excretion is the earliest clinical
A loop diuretic is recommended for the treatment of finding of nephropathy.
hypertension and edema in patients with chronic kidney The normal rate of albumin excretion is less than 20
disease. Thiaziade diuretics are ineffective when GFR is mg/day (15 mcg/min); persistent values between 30 and
less than 50 ml/min. 300 mg/day (20 to 200 mcg/min) in a patient with
Management of blood pressure in CKD, the goal blood diabetes is called microalbuminuria and above 300
pressure depends upon the degree of proteinuria: mg/day (200 mcg/min) are considered to represent
· In patients with proteinuric CKD (500 to 1000 overt diabetic nephropathy.
Table 3: Recommendations for the use of oral anti-diabetic agents in patients with diabetes and renal disease
Class of drug Safety profile in renal disease Remarks
1st generation sulphonylureas Unsafe Risk of prolonged hypoglycaemia
2nd generation sulphonylureas Glipizide safe Glipizide is preferred. Others to be avoided.

Rest unsafe Risk of hypoglycaemiaa
a-Glucosidase inhibitors Unsafe Possible hepatotoxicity
Biguanides Unsafe Risk of lactic acidosis
Thiazolidinediones Safe Volume retention may occur especially with insulin
Meglitinides Repaglinide safe Short half-life and minimal renal excretion of

Nateglinide not repaglinide Significant risk of hypoglycemia with
Completely safe nateglinide
DPP-4 inhibitors Relatively safe Dose adjustment needed for moderate to severe renal
disease
Amylin analogs Safe No dose adjustment required for moderate to severe

renal disease.
No data available for ESRD and dialysis patients.

Establishing the diagnosis of microalbuminuria requires adversely affect renal function are a frequent cause of
the demonstration of a persistent (at least two abnormal worsening renal function. Among patients with chronic
tests) elevation in albumin excretion. Screening for kidney disease, common offenders include
microalbuminuria can be deferred for five years after the aminoglycoside antibiotics (particularly with unadjusted
onset of disease in patients with type 1 diabetes. It should doses), nonsteroidal antiinflammatory drugs, and
begin at diagnosis in patients with type 2 diabetes radiographic contrast material should be avoided or used
because many have had diabetes for several years according to strict guidelines when medically necessary.
before diagnosis.
7. Smoking cessation
Antihypertensive treatment reduces albuminuria and Smoking stoppage is associated with a slower rate of
diminishes its progression even in normotensive diabetic progression of CKD,4. In an increasing number of studies,
patients. In patients with diabetes who have smoking also appears to correlate with an enhanced risk
microalbuminuria or overt nephropathy, ACE inhibitors or of developing kidney disease (primarily nephrosclerosis)
angiotensin receptor blocker (ARB), both lower urinary as well as increasing the rate of progression among those
protein excretion and slow the rate of disease with existing CKD5 .
progression..
Treatment of Chronic Kidney Disease
Strong evidence favors the use of an angiotensin Treatment of CKD mainly comprises of treatment of the
converting enzyme (ACE) inhibitor or ARB as first-line complications of renal dysfunction and Identification and
therapy to lower blood pressure in patients with adequate preparation of the patient in whom renal
proteinuric /Diabetic CKD because these drugs slow the replacement therapy will be required
rate of progression of CKD compared with other
antihypertensive. These salutary effects are mediated by Treatment of the complications of renal dysfunction - A
reducing intraglomerular pressure and inhibition of wide range of disorders may develop as a consequence
angiotensin-driven sclerosing pathways, in part through of the loss of renal function.
inhibition of TGF-beta-mediated pathways.
Volume overload - Sodium and intravascular volume
4. Lipid lowering balance are usually maintained via homeostatic
Elevation in lipid levels also may contribute to the mechanisms until the GFR falls below 10 to 15 mL/min.
development of glomerulosclerosis in chronic kidney Patients with chronic kidney disease and volume overload
disease. Plasma cholesterol concentration above 220 generally respond to the combination of dietary sodium
mg/dL (5.7 mmol/L) was an important risk factor for restriction and diuretic therapy.
progressive renal disease. Lipid lowering (at least with
statins) may slow the rate of progression of chronic kidney Hyperkalemia - In CKD,hyperkalemia may be
disease. precipitated by increased dietary potassium intake,
protein catabolism, hemolysis, hemorrhage, transfusion of
5. Dietary modification and Protein restriction stored red blood cells, and metabolic acidosis associated
The optimal level of protein intake has also not been with decreased urine output. In addition, a host of
determined but it may be reasonable to restrict intake to medications such as angiotensin-converting enzyme (ACE)
0.8 to 1.0 g/kg per day of high biologic value protein, inhibitors, angiotensin receptor blockers (ARBs), and
with the lower value used in patients with progressive CKD spironolactone and other potassium-sparing diuretics such
(stage II & stage III). Some recommend even lower levels, as amiloride, eplerenone, and triamterene can inhibit
such as 0.6 to 0.75 g/kg per day of high value protein in renal potassium excretion.
CKD(stage IV &stage V)patients with close supervision
and dietary counseling3. There is some evidence of Low Metabolic acidosis - There is an increasing tendency to
Protein Diet Supplemented Keto-/Amino Acid in retain hydrogen ions among patients with chronic kidney
Preventing the Progression of CKD. disease 6, 7. There are three major reasons why
treatment of the acidemia may be desirable in patients
6. Avoidance of nephrotoxic drugs with chronic kidney disease.
The administration of drugs or diagnostic agents that

1. Bicarbonate supplementation may slow the Sevelamer carbonate controls the serum phosphate
progression of chronic kidney disease. concentration without inducing hypercalcemia. Lanthanum
2. Bone buffering of some of the excess hydrogen ions is carbonate when chewed also has significant phosphate
associated with the release of calcium and phosphate binding properties. Aluminum hydroxide, Magnesium-
from bone, which can worsen the bone disease. containing antacids, Calcium citrate are other phosphate
3. Uremic acidosis can increase skeletal muscle binders should be avoided.
breakdown and diminish albumin synthesis, leading to
loss of lean body mass and muscle weakness. Mineral bone disease - The principal types of renal bone
4. We recommend alkali therapy to maintain the serum disease include osteitis fibrosa, osteomalacia, and
bicarbonate concentration above 23 meq/L8, 9. If adynamic bone disease.
alkali is given, sodium bicarbonate (in a daily dose of
0.5 to 1 meq/kg per day) is the agent of choice. Osteitis fibrosa results from secondary
Sodium citrate (citrate is rapidly metabolized to hyperparathyroidism. Prevention and/or treatment of
bicarbonate) may be used in patients who are unable osteitis fibrosis in patients with predialysis chronic kidney
to tolerate sodium bicarbonate, disease are primarily based upon dietary phosphate
restriction, the administration of oral phosphate binders,
Hyperphosphatemia - A tendency toward phosphate and the administration of calcitriol (or vitamin D analogs)
retention begins early in renal disease, due to the to directly suppress the secretion of parathyroid hormone.
reduction in the filtered phosphate load and the
hypersecretion of parathyroid hormone (PTH) is initially Anemia - A normocytic, normochromic anemia is
a p p ro p r i a t e, s i n c e P T H c a n c o r r e c t b o t h observed as early as stage 3 CKD and is almost universal
hyperphosphatemia and hypocalcemia. As a result, by stage 4. The primary cause in patients with CKD is
phosphate balance and a normal serum phosphate insufficient production of erythropoietin (EPO) by the
concentration are generally maintained in patients with a diseased kidneys. Additional factors include iron
GFR of greater than 30 mL/min 10. The price paid is deficiency, acute and chronic inflammation with impaired
secondary hyperparathyroidism and the development of iron utilization ("anemia of chronic disease"), severe
renal osteodystrophy. hyperparathyroidism with consequent bone marrow
Once the GFR falls below 25 to 30 mL/min, the addition of fibrosis, shortened red cell survival in the uremic
oral phosphate binders are usually required to prevent environment, Folate or vitamin B12 deficiency and
hyperphosphatemia 11 Hemoglobinopathy. For CKD patients, initiate ESAs when
Hgb levels are less than 10 g/dL and try to maintain goal
One of the preferred agents to bind intestinal phosphate Hgb levels between 11 and 12 g/dL.
is calcium salts, of which the most widely used are calcium
carbonate and calcium acetate. Phosphate binders are However, the goals of ESA treatment are patient-specific.
most effective if taken with meals to bind dietary Adequate bone marrow iron stores should be available
phosphate.Hypercalcemia is a common complication of before treatment with EPO is initiated. The availability of
this regimen. recombinant human EPO has obviated the need for
Table 4: Recommended Ranges for Selected Biochemical Parameters According to Stage of Chronic Kidney Disease12
CKD Stage GFR Range Phosphorus Calcium (corrected) Ca × P Intact PTH

(mL/min/1.73 m2) (mg/dL) (mg/dL) (pg/mL)
30 – 59 2.7 – 4.6 8.4 – 10.2 35 – 70
15 – 29 2.7 – 4.6 8.4 – 10.2 70 – 110
<15, dialysis 3.5 – 5.5 8.4 – 9.5 <55 150 – 300

regular blood transfusions in severely anemic CKD disease, preferably before the plasma creatinine
patients. Frequent blood transfusions in dialysis patients concentration exceeds 1.2 and 1.5 mg/dL in women and
also lead to the development of allo-antibodies that could men, respectively, or the eGFR is less than 60 mL/min per
sensitize the patient to donor kidney antigens and make 1.73 m2. Lower costs and/or decreased morbidity and
renal transplantation more problematic. mortality may be associated with early referral and care
by subspecialists 17-19.
Treatment of Complications of ESRD - Once the patient
has reached the stage of near end-stage renal disease Nephrologists can assist primary care physicians and
(GFR less than 15 mL/min), signs and symptoms related to other specialists in the diagnosis and care of patients at all
uremia begin to occur, such as malnutrition, anorexia, stages of CKD. Because patients with CKD are at risk for a
nausea, vomiting, fatigue, sexual dysfunction, platelet diverse set of adverse outcomes (not just kidney failure),
dysfunction, pericarditis, and neuropathy. referral to other appropriate specialists (eg, cardiologists
for those with complex CVD) should also be considered.
Malnutrition - Malnutrition is common in patients with
advanced chronic renal disease because of a lower food Preparation for and initiation of renal replacement
intake (principally due to anorexia), decreased intestinal therapy - It is important to identify patients who may
absorption and digestion, and metabolic acidosis 15. eventually require renal replacement therapy since
Overall, the diet of most patients with chronic kidney adequate preparation can decrease morbidity and
disease in hemodialysis should provide approximately 30 perhaps mortality. Early identification enables dialysis to
to 35 kcal/kg per day and protein about 1.2 gm/kg per be initiated at the optimal time with a functioning chronic
day16. access and may also permit the recruitment and
evaluation of family members for the placement of a
Uremic bleeding - An increased tendency to bleeding is renal allograft prior to the need for dialysis.
present in both acute and chronic kidney disease,due
primarily to impaired platelet function. A number of Indications for renal replacement therapy - We suggest
different modalities can be used in this setting, including that, among patients with progressive CKD, clinicians must
the correction of anemia, the administration of be vigilant for the presence of symptoms and/or signs of
desmopressin (dDAVP), cryoprecipitate, estrogen, and the uremia and patients should also be fully informed of any
initiation of dialysis. symptoms of uremia to be able to contact their physicians
Indications include :
Referral to nephrologists - Patients with CKD should be · Pericarditis or pleuritis (urgent indication), Progressive
referred to a nephrologist early in the course of their uremic encephalopathy or neuropathy, with signs such
as confusion, asterixis, myoclonus, wrist or foot drop,
Table 5. Criteria for nephrology referral or, in severe, cases, seizures (urgent indication)
· A clinically significant bleeding diathesis attributable
· Urine albumin-to-creatinine ratio (ACR) >300 mg/g
(34 mg/mmol)
to uremia (urgent indication)
· Hematuria not secondary to urological conditions · Fluid overload refractory to diuretics
· Inability to identify a presumed cause of CKD · Hypertension poorly responsive to antihypertensive
· eGFR decline of more than 30 percent in fewer than medications
four months without an obvious explanation
· Difficult to manage complications such as anemia · Persistent metabolic disturbances that are refractory
requiring erythropoietin therapy, and abnormalities to medical therapy. These include hyperkalemia,
of bone and mineral metabolism requiring phosphorus metabolic acidosis, hypercalcemia, hypocalcemia,
binders or vitamin D preparations and hyperphosphatemia.
· Serum potassium greater than 5.5 meq/L, Difficult to
manage drug complications · Persistent nausea and vomiting
· Patients under the age of 18 years, Resistant · Evidence of malnutrition. Relative indications for the
hypertension. initiation of dialysis include decreased attentiveness
and cognitive tasking, depression, persistent pruritus
or the restless leg syndrome. 7. Widmer B, Gerhardt RE, Harrington JT, Cohen JJ.
Serum electrolyte and acid base composition. The
influence of graded degrees of chronic renal
Choice of renal replacement therapy - Once it is
failure. Arch Intern Med 1979; 139:1099.
determined that renal replacement therapy will 8. de Brito-Ashurst I, Varagunam M, Raftery MJ,
eventually be required, the patient should be counseled to Yaqoob MM. Bicarbonate supplementation slows
consider the advantages and disadvantages of progression of CKD and improves nutritional
hemodialysis, peritoneal dialysis (continuous or status. J Am Soc Nephrol 2009; 20:2075.
9. Locatelli F, Valderrábano F, Hoenich N, et al. The
intermittent modalities), and renal transplantation (living
management of chronic renal insufficiency in the
or deceased donor). conservative phase. Nephrol Dial Transplant
2000; 15:1529.
Hemodialysis requires a chronic vascular access to the 10. Delmez JA, Slatopolsky E. Hyperphosphatemia:
bloodstream to permit dialysis to be performed. There its consequences and treatment in patients with
chronic renal disease. Am J Kidney Dis 1992;
are three major types of vascular access for maintenance
19:303
hemodialysis: primary arteriovenous (AV) fistulas; 11. National Kidney Foundation. K/DOQI clinical
synthetic arteriovenous fistulas (AV grafts); and double- practice guidelines for bone metabolism and
lumen, cuffed tunneled catheters. To facilitate placement disease in chronic kidney disease. Am J Kidney Dis
of a permanent vascular access, patients be referred to 2003; 42:S1.
an access surgeon when the patient has late stage 4 CKD, 12. Modified from National Kidney Foundation
DOQI™ Kidney Disease Outcomes Quality
defined by an estimated GFR of less than 20 to 25 mL/min Initiative. Am J Kidney Dis 43:S1–S201, 2004.
per 1.73 m2 [75]. Referral of patients with CKD to a 13. Stefanski A, Schmidt KG, Waldherr R, Ritz E. Early
transplant center should occur when the GFR decreases to increase in blood pressure and diastolic left
less than 30 mL/min or, among diabetics, when the GFR is ventricular malfunction in patients with
between 30 to 40 mL/min. glomerulonephritis. Kidney Int 1996; 50:1321.
14. Kopple JD, Greene T, Chumlea WC, et al.
Relationship between nutritional status and the
References glomerular filtration rate: results from the MDRD
1. Agarwal SK, Dash SC, Irshad M et al. Prevalence of study. Kidney Int 2000; 57:1688.
chronic renal failure in adults in Delhi, India Nephrol 15. Garg AX, Blake PG, Clark WF, et al. Association
Dial Transplant 2005; 20: 1638–1642 between renal insufficiency and malnutrition in
2. Data from: National Kidney Foundation. K/DOQI older adults: results from the NHANES III. Kidney
clinical practice guidelines for chronic kidney Int 2001; 60:1867.
disease: evaluation, classification, and 16. Ahmed, K, Kopple, J. Nutritional management of
stratification. Am J Kidney Dis 2002; 39(2 Suppl renal disease. In: Primer on Kidney Diseases,
1):S1. Greenberg, A (Ed). Academic Press, San Diego,
3. Ikizler, IA. Nutrition and kidney disease. In: Primer CA, 1994, p. 289.
on Kidney Diseases, Greenberg, A (Ed), Elsevier 17. Stack AG. Impact of timing of nephrology
Saunders, Philadelphia, 2005, p. 496. referral and pre-ESRD care on mortality risk
4. Orth SR. Effects of smoking on systemic and among new ESRD patients in the United States.
intrarenal hemodynamics: influence on renal Am J Kidney Dis 2003; 41:310.
function. J Am Soc Nephrol 2004; 15 Suppl 1:S58. 18. Kessler M, Frimat L, Panescu V, Briançon S. Impact
5. Orth SR, Hallan SI. Smoking: a risk factor for of nephrology referral on early and midterm
progression of chronic kidney disease and for outcomes in ESRD: EPidémiologie de l'Insuffisance
cardiovascular morbidity and mortality in renal REnale chronique terminale en Lorraine (EPIREL):
patients--absence of evidence or evidence of results of a 2-year, prospective, community-
absence? Clin J Am Soc Nephrol 2008; 3:226. based study. Am J Kidney Dis 2003; 42:474.
6. Uribarri J, Douyon H, Oh MS. A re-evaluation of the 19. Khan SS, Xue JL, Kazmi WH, et al. Does
urinary parameters of acid production and predialysis nephrology care influence patient
excretion in patients with chronic renal acidosis. survival after initiation of dialysis? Kidney Int
Kidney Int 1995; 47:624. 2005; 67:1038.
Contrast and the Kidney
Dr NP SIngh
Introduction alternative etiology”.

Technical development and increasing An arbitrary range of values of between
availability of interventional procedures 25% and 50% (an increase in absolute
has led a large number of patients to values of 0.5–1.0 mg/dL) increase in
being exposed to iodinated contrast serum creatinine levels from baseline has
medium. There is a paucity of data on been suggested to define contrast-
patients undergoing such procedures in induced nephropathy. Other suggested
India. Figures available for other definitions include the following: a rise in
countries, such as USA, suggests that on a serum creatinine levels of more than
average there are more than 13,22,000 100%, a rise in serum creatinine levels of
diagnostic cardiac catheterizations and more than 1 mg/dL, a postprocedural
12,65,000 percutaneous transluminal serum creatinine level greater than 5
coronary angioplasty procedures, which mg/dL, or acute renal failure requiring
is just two of the many ways in which dialysis.
contrast is used. Regular use of the
contrast agents in imaging modalities Contrast Agents
exposes patients to risks associated with Various contrast agents used in clinical
the use of these agents. Contrast induced practice are summarized in Table 1.
nephropathy (CIN) is one such threat, a
potentially avoidable adverse event Epidemiology
related with the use of iodinated contrast The incidence of contrast-induced
media (ICM). In addition, it is the third n e p h ro p a t hy va r i e s m a r ke d l y,
most general cause of hospital-acquired depending on the definition used and on
acute renal failure. Patients with pre- other variables such as the type of
existing risk factors such as severe renal radiology procedure performed, the
insufficiency at baseline with or without dose and type of contrast agent
diabetes, advanced age, congestive administered, the differing patient
heart failure and dehydration, are more populations in regard to number and
likely to be at-risk. These complications type of risk factors, and the length of
are important as the consequences are patient follow-up. An overall incidence
serious or even life threatening. Thus, it is of 14.5% was recently quoted in a large
impor tant implement preventive epidemiologic study but rates may vary
strategies, and to have a knowledge of from 0% to 90%, depending on the
the clinical presentation and subsequent presence of risk factors. Incidence
management of the condition. among patients with diabetes has been
reported to be 9–40% in patients with
Dr NP Singh
Definition mild-to-moderate CKD and 50–90% in
Director The definition, provided by EUSR those with severe CKI. The incidence in
Medicine & Allied Specialties (European Union Special Representative) the general population is much lower
Sr Consultant in Nephrology guidelines implies “Impairment in renal and has been calculated to be less than
& Medicine function (an increase in serum 2%.
Pushpanjali Crosslay Hospital creatinine by more than 25%) The in-hospital mortality rates were
Delhi-NCR occurring within 3 days following the 1.1% for patients with no contrast-
intravascular administration of induced nephropathy compared with
contrast media and the absence of 7.1% for those with nephropathy alone,
Table 1. Classification of contrast agents [10] Some important risk factors are summarized below.
1. Chronic Kidney Disease
High Low- Iso- Irrespective of cause, preexisting impairment of renal
osmolar osmolar osmolar
function appears to be the most important risk factor. The
(≈2,000 (600 to 900 (≈300
risk of CIN is inversely related to the calculated
mOsm/L) mOsm/L) mOsm/L)
estimated GFR (eGFR). An eGFR of <60 ml/ min/1.73
Ionic Iothalamate Ioxaglate m2 represents significant renal dysfunction and is used to
Diatrizoate define the patient at high risk for developing CIN.
Metrizoate
Non-ionic - Iohexol Iodixanol 2. Diabetes Mellitus

(Omnipaque) (Visipaque) Diabetes mellitus with associated renal insufficiency has
Ioversol
Iopamidol been identified as an independent risk factor for contrast
Iopromide nephropathy, with as many as 56% of those who develop
Ioversol the condition progressing to irreversible renal failure.
Diabetes itself is not an independent risk factor for the
and up to 35.7% for those with nephropathy requiring development of contrast-induced nephropathy. More
dialysis. Similar findings were noted in a study of more recent research has failed to corroborate this connection.
than 16,000 patients undergoing contrast-enhanced For example, in a prospective trial of patients with
examinations (CT of the head and body, cardiac diabetes none of the 85 patients with diabetes and
angiography, and peripheral angiography). normal renal function developed clinically significant
renal impairment (defined as an increase of > 50% in
Risk Factors serum creatinine levels).
3. Reduction of Effective Intravascular volume

Table 2: Risk factors associated with CIN Reduction of effective intravascular volume (due to
congestive heart failure, liver cirrhosis, or abnormal fluid
Non-modifiable risk
losses), prolonged hypotension (especially when induced
factors
Diabetes mellitus
by intensive antihypertensive treatment combined with
Renal disease or Solitary angiotensin-converting enzyme inhibitors and diuretics,
kidney most notably furosemide), and dehydration have been
Age >70 yrs reported as contributing to prerenal reduction in renal
Previous chemotherapy perfusion, thus enhancing the ischemic insult of contrast
Organ transplant
Cardio-Vascular disease
media.
- hypertension,
- congestive heart disease 4. Nephrotoxic Drugs
Directly nephrotoxic drugs (eg, cyclosporine A,
- cardiac or peripheral vascular disease aminoglycosides, amphotericin, and cisplatin), those that
HIV
inhibit the local vasodilatory effects of prostaglandins
Protein urea
(eg, nonsteroidal antiinflammatory drugs [NSAIDs]) and
Modifiable risk factors diuretics especially furosemide (due to intravascular
Type and volume of contrast media injected volume depletion), have been reported to render the
Sepsis or acute hypotension kidney more vulnerable to nephrotoxic contrast agents.
Dehydration or volume contraction
- CHF - Cirrhosis
Although all these medications are known to induce renal
- Nephrotic syndrome - Diuretics especially furosemide damage, their individual roles as independent risk
- Fluid losses factors of contrast-induced nephropathy have yet to be
Nephrotoxic Drugs – determined in large prospective clinical trials.
- Loop diuretics - Amphotericin B
- Aminoglycosides - Vancomycin
5. Multiple Myeloma
- NSAIDs
Multiple myeloma has been reported as a risk factor for
CIN. It has been argued that high amounts of protein in the 3. Abnormal baseline serum creatinine level
tubular lumen with concomitant contrast material load 4. The use of HOCM [meglumine diatrizoate]
may cause an obstructive nephropathy, a mechanism that 5. Preexisting renal disease.
is thought to be central to the development of renal These authors showed that the probability of developing
insufficiency in patients with nephrotic-range proteinuria the condition increased as the number of factors
secondary to multiple myeloma. increased, with the most marked jump in serum creatinine
levels seen when three or more risk factors were present
6. Contrast agents related factors (from < 5% increase with two factors to > 30% increase
Volume of contrast agent with three factors).
Large doses and multiple injections of contrast media
within 72 hours increase the risk of the patient's Pathogenesis
developing contrast-induced nephropathy. However, cut-
off values have not been defined, yet. The exact underlying mechanisms of nephrotoxicity have
yet to be fully elucidated but are likely to involve the
Route of administration interplay of several pathogenic factors (Fig 2). Intrinsic
The route of administration is also important, with contrast causes include the following: increased vasoconstrictive
media being more nephrotoxic when administered forces, decreased local prostaglandin- and nitric oxide
intraarterially. This effect is thought to be due to the fact (NO)-mediated vasodilatation, a direct toxic effect on
that the acute intrarenal concentration of contrast media is renal tubular cells with damage caused by oxygen free
much higher after intraarterial rather than IV injection. radicals, increased oxygen consumption, and increased
intra tubular pressure secondary to contrast-induced
Osmolarity diuresis, increased urinary viscosity, and tubular
Similarly, the osmolarity of the contrast media plays an obstruction, all culminating in renal medulla ischemia.
important role with large clinical studies and meta- Intrinsic causes act in concert with harmful extrinsic (pre
analyses indicating that the use of an LOCM substantially renal) causes such as dehydration and decreased
reduces the risk of nephropathy in high-risk patients effective intravascular volume.
compared with the use of HOCM. LOCM causes less
discomfort and fewer cardiovascular and anaphylactic Clinical Feature
adverse reactions than HOCM but is more expensive.
Clinical Features and Treatment
Risk Assessment Contrast-induced nephropathy most commonly manifests
as a nonoliguric and asymptomatic transient decline in
Since occurrence of CIN is highly related to presence of renal function. The serum creatinine level begins to rise
preprocedural risk factors, many attempts have been within 24 hr of contrast administration, usually peaks
made to develop a risk assessment score. The European within 3–5 days, and returns to baseline within 10–14
Society of Urogenital Radiology recommends that only days. Oliguric acute renal failure requiring hemodialysis
elevated serum creatinine levels (particularly secondary can also occur. This condition presents with oliguria (24-hr
to diabetic nephropathy), dehydration, congestive heart urine volume < 400 mL) within 24 hours of contrast
failure, age greater than 70 years, and concurrent administration and typically persists for 2–5 days.
nephrotoxic drugs be used to establish risk. Morbidity and mortality rates are significantly higher in
this group of patients when compared with those who
Cochran et al presented a point system (tally of risk have nonoliguric renal failure.
factors) model to predict the probability of developing
contrast-induced renal insufficiency. They found five risk Urinary epithelial cell casts, debris, and urate and calcium
factors that were shown to predict at-risk patients with oxalate crystals are nonspecific findings in contrast-
high probability. These are: induced nephropathy. Low urinary sodium and fractional
1. Age > 55 years excretion of sodium (< 1%) have been reported as being
2. Proteinuria distinctive characteristics of this condition, but these

Contrast Media
PGE Endothelin Systemic

Vasopressin Hypoxaemia Osmotic load
ANP
Blood viscosity Distal tubule
Adenosine ¯ PGI2
¯Blood flow ¯O2 delivery O2 consumption
Direct cellular toxicity Renal medullary hypoxia
Contrast induced nephropathy (CIN)
ANP, atrial natriuretic peptide; PGE, prostaglandin; PGI, prostacyclin
findings have not consistently been shown to be specific for 1. Hydration

contrast-induced nephropathy. A persistent nephrogram Hydration is the primary intervention for preventing
on radiography or CT 24 hours after contrast contrast nephropathy. Several studies both in animals, and
administration is also said to be suggestive of a diagnosis humans have demonstrated hydration with saline infusions
of contrast-induced nephropathy but is not a consistent or to be beneficial in preventing contrast-induced
a specific finding. nephropathy.
More recently a prospective, single-center randomized
Treatment of established contrast-induced nephropathy trial of 119 patients by Merten et al has suggested that
should start with the recognition of renal impairment after the use of sodium bicarbonate hydration is superior to
the study. In patients at higher risk, renal function should be sodium chloride hydration. Rates of contrast-induced
carefully monitored by measuring serum creatinine levels nephropathy were significantly lower in the sodium
before and once daily for 5 days after the radiographic bicarbonate group (1.7%, n = 1) when compared with the
procedure. After contrast-induced nephropathy is sodium chloride group (13.6%, n = 8) when both cohorts
identified, the subsequent management of this condition is were administered 154 mEq/L of either solution IV.
the same as that for acute renal failure due to other
causes. Admission to the hospital and subsequent judicious 2. N -ACETYLCYSTEINE
monitoring of serum electrolyte levels are required to There is some evidence that reactive oxygen species have
prevent hyperkalemia, hyponatremia, a role in renal damage caused by contrast agents [57, 74, 77-78].
hyperphosphatemia, hypocalcemia, and metabolic N-acetylcysteine (NAC), a thiol-containing antioxidant, is
acidosis associated with acute renal failure. More severe thought to act either as a free-radical scavenger or as a
cases may require temporary hemodialysis, but a minority reactive sulfhydryl compound that increases the reducing
of patients who do not respond to conservative treatment capacity of the cell. NAC has been shown to ameliorate
will require permanent dialysis or kidney transplantation. ischemic renal failure in the animal model[84] and has been
used successfully to reduce the toxic effects of a variety of
Preventive Treatments experimentally or clinically induced ischemia-reperfusion
syndromes of the heart, kidney, lung, and liver [85-86].
Several drug interventions based on one or more of the
pathogenic mechanisms outlined earlier, have been tested In a recent meta-analysis of 41 randomized trials that
in trials for prophylaxis against the development of administered N-acetylc ysteine, theophylline,
contrast-induced renal dysfunction. fenoldopam, dopamine, iloprost, statin, furosemide, or

mannitol to the treatment group; found that preprocedural 6. Dopamine agonists
treatment with N-acetylcysteine was more effective in Dopamine is a potent vasodilator of the renal arteries. It
reducing the risk for contrast-induced nephropathy than has been found to not benefit in any treatment but like
the hydration alone. diuretics, dopamine had a deleterious rather than a
These recent studies, coupled with the favorable side protective effect on renal function in patients with
effect profile of NAC and its low cost, mean that NAC has diabetes.
gained favor in many centers as a preventive therapy, Recent evidence show a selective dopamine type 1
particularly in the high-risk group undergoing coronary receptor agonist, fenoldopam mesylate, may be useful in
interventions. preventing contrast-induced nephropathy. It produces
More recently, Briguori et al [98] reported a protective vasodilatation in vessels rich in dopamine type 1
effect of a high dose (1,200 mg twice daily) versus a receptors such as renal, mesenteric, and peripheral
standard dose (600 mg twice daily) along with saline arteries but does not stimulate dopamine type 2 or
hydration. adrenergic receptors, even at high doses. It is a potent
relaxant of glomerular arterioles, preferentially acting
3. Contrast Media on the efferent arterioles, and is six times more potent
Low osmolar contrast media have been shown to be than dopamine in increasing renal blood flow.
associated with reduced risk of nephropathy especially in
high risk patients. Observational studies reported rather low rates of CIN in
With the introduction of low-osmolar and iso-osmolar high-risk patients treated with fenoldopam. In a double-
contrast media, a reduction in the incidence of CIN has blind, randomized, placebo-controlled pilot trial, the
been observed [4, 8, 50-53]. Low-osmolar contrast media have combination of fenoldopam and hydration, compared
gained widespread clinical acceptance because of fewer with hydration alone, resulted in an increase in renal
adverse effects than high-osmolar contrast media, plasma flow, a decrease in peak serum creatinine level 72
particularly in high-risk patients with an elevated hours after exposure to contrast media, and a trend
preprocedural serum creatinine. The Rudnick toward decreased incidence of CIN (21% and 41%,
demonstrated that patients with preexisting renal respectively; p=0.14). Two other prospective randomized
insufficiency alone or combined with diabetes mellitus had trials showed negative results.
a significantly lower risk of CIN when low-osmolar contrast
media are used. 7. Hemodialysis and Hemofiltration
Several studies examined the effect of hemodialysis,
4. Diuretics immediately after exposure to contrast media, in
It has previously been recommended that furosemide or preventing renal function deterioration in patients with
mannitol administered in conjunction with a saline infusion preexisting renal disease. All these studies provided
offers better protection of renal function, but consistent consistent results, showing that prophylactic hemodialysis
results have not been obtained. Indeed, an exacerbation does not diminish the rates of CIN.
of contrast-induced nephropathy (defined as an Two studies by Marenzi et al [112-113] investigated the effect
increased of > 0.5 mg/dL of serum creatinine levels) of continuous venovenous hemofiltration in prevention of
occurred with the concomitant use of furosemide. CIN in patients with severe chronic renal insufficiency
(serum creeatinine >2 mg/dL) in comparison with
5. Theophylline intravenous hydration. Increase of creatinine >25% and
Adenosine, a potent vasoconstrictive agent, has been inhospital mortality were significantly lower in group with
implicated as a mediator in tubulo-glomerular feedback, hemofiltration.
a mechanism that may have a role in the pathogenesis of
contrast-induced nephrotoxicity. Theophylline acts as a Guidelines for Prevention
nonspecific adenosine receptor antagonist and may be
given as an IV bolus of 2.5–5 mg/kg of body weight Since occurrence of CIN is proportionately related to
before administration of contrast agent or orally for three presence of risk factors, it essential is to estimate the
consecutive days before contrast injection. patient's risk for CIN. The commonly used methods for

identifying patients at risk include use of patient preventing CIN has not been fully established; yet several
questionnaires, review of medical history and preventive measures are supported by clinical trial data.
measurement of SCr levels prior to administration of CM. Fig 3 provides an algorithm adapted from guidelines
Calculation of the eGFR should be encouraged. developed by Canadian Association of Radiologists,
In case of low risk patients, good oral hydration is all that outlining the management of patients undergoing contrast
required. For high risk cases, optimal strategy for procedures.
General guidelines for all patients with GFR <60 mL/min: Table 6: Dose of N-Acetylcysteine to prevent CIN [131]
· Consider alternate imaging studies not requiring
iodinated contrast medium (CM). Tolerating PO intake?
· Hold nephrotoxic drugs for 48 hours prior to CM. 600-1200 mg capsules PO Q12h X 4 doses
· Use iso-osmolar or low-osmolar CM. 2 doses pre-contrast and 2 doses post-contrast is optimal
· Avoid high-osmolar CM.
· Minimize contrast volume and avoid repeat contrast Feeding tube or NG-access?
studies within 72 hours if possible Acetylcysteine 600-1200 mg (3 mL of 20% soln.) liquid
PT/NG Q12h x 4 doses total
Moderate-to-High risk for CIN Emergent Procedure?

· IV 0.9% Saline or NaBicarb 1 dose before and 3 doses post cath or procedure is
· Follow-up GFR 48 hours post CM acceptable (Q12h x 4 doses total)
Fig 3: Algorithm for prevention of CIN IV Acetylcysteine?

(adapted and modified from the consensus guidelines 600-1200 mg IV x 1 over 15 minutes, then 600-1200 mg
developed by Canadian Association of Radiologists [129] PO/PT q12h x 4 doses post-procedure:
For a high risk patient with acute ST-elevation MI
undergoing cardiac catheterization.
Table 4: Dose of peri-procedural Intravenous fluids

to prevent CIN [87] Guidelines for patients taking Metformin
The biguanide metformin are used in non-insulin
IVF = 1 mL/kg/hr 12 hours pre & 12 hours post contrast*
dependent diabetes mellitus. Approximately 90% of
(24 hour total infusion duration)
(*NS preferred IVF ) metformin is eliminated via the kidneys in 24-hour Renal
insufficiency (GFR<70 ml/min) will lead to retention of
CHF or left ventricular ejection fraction (LVEF) < 40%? these biguanides in the tissues and the potential for the
0.5 ml/kg/hr 12 hrs pre & post contrast (24 hour total development of fatal lactic acidosis [132]. The use of
infusion duration)
contrast media in patients receiving metformin should be
Emergent procedure? carried out with care. Contrast media can induce a
Fluid bolus of 500-1000 ml prior to procedure. Hydration reduction in renal function, leading to retention of
during procedure and/or 12 hrs afterward. [ if possible] metformin that may induce lactic acidosis. There is no
(dependent on clinical status) conclusive evidence indicating that the intravascular use
of contrast media precipitated the development of
metformin induced lactic acidosis in patients with normal
Table 5: Dose of Bicarbonate to prevent CIN [130] renal function. The complication has almost always been
IVF = 150 mEq of sodium bicarbonate in 1 liter of D5W observed in Type 2 diabetic patients with abnormal renal
3 ml/kg bolus 1 hour prior to procedure AND 1 mL/kg/hour function before injection of contrast media. Serum
during and for 6 hours post-procedure creatinine should always be monitored to check that it is
within the normal range before administration of
Glycemic control issues (including patients with
metformin is resumed. The CMSC of the ESUR (Table 7) has
diabetes)?
Consider mixing sodium bicarbonate in 1 liter of sterile produced a new guideline on the use of metformin and
water instead of D5W contrast media.

Table 7: European Society of Urogenital Radiology
Contrast media induced nephrotoxicity: A
(ESUR) guidelines for the administration of contrast
c o n s e n s u s r e p o r t . E u r Ra d i o l 1 9 9 9 ;
media to diabetics taking metformin [3]
9:1602–1613.
4. Gleeson TG, Bulugahapitiya S. Contrast-Induced
1. Serum creatinine level should be measured in every
Nephropathy. AJR 2004; 183:1673-1689
diabetic patient treated with biguanides prior to
5. Katzberg RW. Urography into the 21st century:
intravascular administration of contrast media. Low-osmolar
new contrast media, renal handling, imaging
contrast media should always be used in these patients.
characteristics, and nephrotoxicity. Radiology
2. Elective studies 1997; 204: 297–312.
a) If the serum creatinine is normal, the radiological 6. Parfrey PS, Griffiths SM, Barrett BJ, et al Contrast
examination should be performed and intake of material-induced renal failure in patients with
metformin stopped from the time of the study. The use of diabetes mellitus, renal insufficiency, or both.
metformin should not be resumed for 48 h and should NEJM 1989; 320:143-153
only be restarted if renal function/serum creatinine 7. McCullough PA, Wolyn R, Rocher LL, Levin RN,
remains within the normal range. O'Neill WW. Acute renal failure after coronary
b) If renal function is abnormal, the metformin should be intervention: incidence, risk factors, and
stopped and the contrast study should be delayed for 48 relationship to mortality. Am J Med1997;
h. Metformin should on be restarted 48 h later, if renal 103:368-374
function/serum creatinine is unchanged. 8. Lautin EM, Freeman NJ, Schoenfeld AH, et al
Radiocontrast-associated renal dysfunction: a
3. Emergency cases comparison of lower-osmolality and conventional
a) If the serum creatinine is normal, the study may proceed high-osmolality contrast media. AJR1991;
as suggested for elective patients. 157:59-65
b) If the renal function is abnormal (or unknown), the 9. Levy EM, Viscoli CM, Horwitz RI. The effect of
physician should weigh the risks and benefits of contrast acute renal failure on mortality: a cohort analysis.
administration. JAMA1996; 275:1489-1494
10. Kozak M, Robertson BJ, Chambers CE. Cardiac
Alternative imaging techniques should be considered. If catheterization laboratory: Diagnostic and
contrast media administration is deemed necessary and the therapeutic procedures in the adult patient. In:
following precautions should be implemented: Kaplan, JA, editor. Kaplan's Cardiac Anesthesia,
· Metformin therapy should be stopped 5th ed. p. 307.
· The patient should be hydrated, eg, at least 100 ml h21 11. Schwab SJ, Hlatky MA, Pieper KS, et al Contrast
of soft drinks or intravenous saline up to 24 h after nephrotoxicity: a randomized controlled trial of a
contrast medium administration – In warm areas more nonionic and an ionic radiographic contrast
fluid should be given
agent. N Engl J Med 1989; 320:149–153
· Monitor renal function (serum creatinine), serum lactic 12. Rudnick MR, Goldfarb S, Wexler L, et al
acid and pH of blood
Nephrotoxicity of ionic and nonionic contrast
· Look for symptoms of lactic acidosis (vomiting,
media in 1,196 patients: a randomized trial—the
somnolence, nausea, epigastric pain, anorexia,
Iohexol Cooperative Study. Kidney Int 1995;
hyperpnoea, lethargy, diarrhea and thirst). Blood test
results indicative of lactic acidosis: pH<7.25 and lactic 47:254–261
13. Weisberg LS, Kurnik PB, Kurnik BR. Risk of
acid >5 mmol
Radiocontrast nephropathy in patients with and
without diabetes mellitus. Kidney Int 1994;
45:259–265
References
14. Cochran ST, Wong WS, Roe DJ. Predicting
1. Heart Disease and Stroke Statistics 2008 Update:
angiography- induced acute renal function
A Report from the American Heart Association
impairment: clinical risk model. AJR 1983;
Statistics Committee and Stroke Statistics
141:1027–1033
Subcommittee. Circulation 2008; 117: e133-137
15. Harkonen S, Kjellstrand CM. Exacerbation of
2. Tublin ME, Murphy ME, Tessler FN. Current concepts
diabetic renal failure following intravenous
in contrast media-induced nephropathy. AJR1998;
pyelography. Am J Med 1977;63:939–946
171:933-939.
16. Manske CL, Sprafka JM, Strony JT, Wang Y.
3. Morcos SK, Thomsen HS, Webb JAW and members
Contrast nephropathy in azotemic diabetic
of contrast media safety committee of the
patients undergoing coronary angiography. Am J
European Society of Urogenital Radiology (ESUR).
Med 1990; 89:615–620

An Approach to the patient with Obstructive Kidney Disease
Dr Shailesh Chandra Sahay
Obstruction of the urinary tract can occur Obstructive uropathy refers to the
before or after birth. The cause of functional or anatomic obstruction of
obstruction may be congenital or urinary flow at any level of the urinary
acquired and benign or malignant. The tract. Obstructive nephropathy is
site of obstruction can vary from present when the obstruction causes
pelvicalyceal system to urethral meatus. functional or anatomic renal damage.
The severity of the obstruction is related
with the extent or degree of obstruction Clinical feature
(partial or complete, unilateral or The clinical signs and symptoms of
bilateral), its chronicity (acute or chronic) obstructive uropathy are variable. It
and the baseline condition of the kidneys. depends upon the time course over which
These may ultimately lead to permanent it develops and whether or not both sides
renal damage. are involved. Acute unilateral
obstruction presents with symptoms of
Hydronephrosis is the dilation of the renal colic. Chronic unilateral obstruction
renal pelvis or calyces. It may be is clinically silent and diagnosed on
associated with obstruction but may be incidental detection of hydronephrosis
present in the absence of obstruction. on imaging. Acute or chronic bilateral
Table 1. Etiology of Obstructive Uropathy
Site of obstruction Etiology

Kidney Congenital disease- PCKD, Primary Pelviureteric junction (PUJ)
obstruction, Renal cyst, Aberrant vessels at PUJ
Neoplastic- Wilm's tumor, renal cell carcinoma, Upper tract

transitional cell carcinoma, multiple myeloma
Inflammatory- Tuberculosis, Echinococcus infection
Metabolic- stone
Traumatic
Ureter Congenital- Stricture, ureterocele, ureterovesical reflux,
ureteral valve, ectopic kidney, preureteric vena cava, Prune-
belly syndrome
Neoplastic- TCC of ureter, Metastatic
Inflammatory- Tuberculosis, Schistosomiasis, Abscess,
Endometriosis,
Dr Shailesh Chandra Sahay Miscellaneous- retroperitoneal fibrosis, Pelvic lipomatosis,
Consultant Urologist
Aortic aneurysm, Urinoma, Pregnancy, Lymphocele
Department of Urology Bladder and Urethra Congenital- Posterior urethral valve, phimosis,
urethral stricture, hypospadias and epispadias, hydrocolpos
Pushpanjali Crosslay Hospital
NCR-Delhi Neoplastic - Bladder carcinoma, prostate carcinoma,
carcinoma of urethra and penis
Inflammatory- Prostatitis, paraurethral abscess
Miscellaneous- Benign prostatic hypertrophy (BPH),
neurogenic bladder

obstruction presents with decrease urine output and Doppler ultrasonography gives an indication of functional
uraemia. Patient usually presents with vague symptoms of status of kidney. It allows measurement of the renal
flank discomfort, vomiting, feelings of fullness, nonspecific resistive index (RI), which has been used as a parameter to
lethargy and urinary tract infection. Vomiting is induced assess renal obstruction. The RI is defined as peak systolic
by increased ureteral pressure that leads to increases velocity (PSV) minus the end-diastolic velocity (EDV)
pyloric sphincter pressure hence interfering with gastric divided by the PSV. Values greater than 0.7 reflects
motility (renogastric reflex). elevated resistance to blood flow and thus suggesting
obstructive uropathy2. Doppler determination of RI is a
Diagnosis valuable adjunct to routine sonographic evaluation of
Ultrasonography urinary tract.
Renal ultrasonography is the initial investigation in the
evaluation of suspected urinary tract obstruction. It gives Excretory Urography/ Intravenous pyelography
information about renal parenchymal thickness, Intravenous pyelography (IVP) has been considered as the
pelvicalyceal system dilatation. Hydronephrosis is an “gold standard” for the evaluation of the upper urinary
anatomic diagnosis. However, caliectasis and pelviectasis tract. Now-a-days, it has been gradually supplanted by
both may be present in an unobstructed system. Renal other modalities for many of its prior indications. It
sinus cysts can give false impression as hydronephrosis. provides both anatomic and functional information. Acute
Conversely, hydronephrosis may not be prominent early in urinary obstruction may be inferred from the functional
acute obstruction. Presence of an intrarenal collecting abnormality of a delayed nephrogram and pyelogram on
system or dehydration may lead to false-negative the affected side. Delayed images may then ultimately
interpretations. Ultrasonography has 35% false-negative reveal the anatomic level of obstruction. Parenchymal
rate in acute obstruction, underscoring the need to thinning, extreme calyceal blunting, and ureteral
correlate the clinical picture carefully with the radiologic tortuosity may indicate the chronicity of obstruction.
findings1.
Table 2. Investigations in Obstructive Uropathy The utility of IVP is limited in those with renal insufficiency.
Furthermore, the risk of contrast nephropathy increases
Investigation Utility with increasing serum creatinine. IVP, therefore, should not
be performed in patients with renal insufficiency, those at
Ultrasound abdomen Detects hydronephrosis, urinary
tract stones Measure renal higher risk for developing contrast-induced nephropathy,
parenchymal thickness, residual or those with history of contrast allergy. Radiation
urine volume in bladder, prostate
size, renal resistive index. exposure limits its utility in pregnancy3.
Intravenous Functional and anatomical Retrograde Pyelography

pyelography information of kidneys and
urinary (IVP) tract
Retrograde pyelography (RGP) accurately defines
ureteral and pelvicalyceal system anatomy. It defines the
Retrograde Defines ureteral and location of an obstructive lesion and its extent. It is useful in
pyelography pelvicalyceal system anatomy in
those cases where IV contast can
those who have renal insufficiency or have other risks for
not be given receiving intravenous iodinated contrast material
Whitaker test Detect and differentiate degree

Antegrade Pyelography
of urinary obstruction
This technique may be helpful when other imaging studies
Renal dynamic scan Measure GFR and detect any do not adequately define collecting system or ureteral
obstruction in urinary drainage
anatomy and when RGP is not technically feasible.
from kidney
CT Scan and MRI An accurate method to detect Whitaker Test

abdomen urinary stones, mass, First described by Whitaker in 1973, this study involves
cyst. Urography provides an
anatomical picture of urinary measurement of renal pelvic pressure during infusion of
tract either saline or contrast material into the collecting system

through a percutaneous needle at a fixed rate of 10 when obstruction is demonstrated, both the F-15 and F +0
mL/min4. A catheter is placed in the bladder to monitor sequences can induce obstructed patterns in previously
intravesical pressure, which is subtracted from the equivocal cases8.
measured collecting system pressures to calculate the
“true pressure” within the pelvis. A true intrapelvic CT Scan and MRI
pressure of less than 15 cm H2O is considered normal, This modality has now replaced IVP as an initial imaging
greater than 22 cm H2O indicative of obstruction, and study in those with suspected ureteral obstruction,
between 15 and 22 cm H2O indeterminate. Although its especially in an acute setting. In their landmark study,
reliability to detect obstruction and differentiate degree Smith and coauthors (1995) demonstrated the efficacy of
of obstruction has been established in animal models5. unenhanced spiral CT in the evaluation of possible
Studies have reported a sensitivity and specificity of only ureteral obstruction, prospectively comparing it with IVP In
the detection of ureteral calculi, CT has a sensitivity of
79% and 50% in kidney transplantation patients6.
97%, specificity of 96%, and overall accuracy of 97%9.
Nuclear Renography/ Renal Dynamic scan At this time, CT is the most accurate radiologic study for the
Renal dynamic scan is a useful, noninvasive test for diagnosis of ureteral calculi.
evaluating patients with suspected obstruction. It provides
a functional assessment without exposure to iodinated CT directly demonstrates calculi classically considered
contrast. Radiopharmaceuticals for renography are radiolucent on X ray, including uric acid, xanthine,
selected on the basis of the function to be studied. The dihydroxyadenine, and many drug-induced stones.
glomerular agent Tc 99m DTPA and the tubular agent Tc Exceptions, however, are calculi composed of protease
99m MAG3 are most commonly used. All tracers are inhibitors, which are not visualized by CT 10. Secondary CT
administered intravenously, and their uptake and signs of obstruction such as ureteral dilatation,
subsequent clearance is evaluated and quantitated nephromegaly, perinephric stranding or fluid can
scintigraphically. From these data, relative renal function facilitate the diagnosis of acute obstruction.
can be calculated. Obstruction can be assessed by
measuring the clearance curves, either from a visual The role of magnetic resonance urography (MRU) is still
assessment of the pattern or from calculation of the half- being defined11. Although this study accurately identifies
time (time at which 50% of the tracer is eliminated from hydroureteronephrosis, a limitation is its inability to
the collecting system). By convention, a half-time less than demonstrate either calculi or the ureteral anatomy of
10 minutes is considered normal, greater than 20 minutes unobstructed systems. However absence of ionizing
is considered obstructed, and between 10 and 20 minutes radiation has allowed its utilization in the assessment of
is equivocal. Tracer clearance can be spuriously delayed pregnant patients with hydronephrosis.
because of renal insufficiency and the presence of
vesicoureteral reflux, and some have suggested that renal Management
immaturity in neonates may generate false-positive Unilateral ureteral obstruction associated with urinary
studies7. tract infection or Pyonephrosis and bilateral ureteral
obstruction with renal failure should be immediately
In order to detect obstruction, a high-flow state may be drained.
necessary. Patients therefore should be well hydrated to
prevent misinterpretation related to low-flow states. Renal Drainage
Theoretically, bladder catheterization should be There are two ways to drain the kidney in emergency
performed to maintain low intravesical pressure. settings- Retrograde double J stenting and percutaneous
However, in clinical practice this is utilized only in certain nephrostomy tube placement. These measures may allow
cases such as suspected lower urinary tract obstruction, temporary drainage until a definitive procedure is
vesicoureteral reflux, neurogenic or noncompliant performed. Urine specimens for urinalysis and culture
bladder, or low-lying, pelvic kidneys from which the renal should be obtained from the obstructed renal unit at the
s i g n a l m a y b e o b s c u r e d by i n t r a v e s i c a l time of relief of obstruction. Antibiotic therapy is started if
radiopharmaceutical7. Although an F +20 study is reliable there are clinical signs and symptoms of infection.

adults16. Sometime the patient may prefer life with a stent
or percutaneous nephrostomy.
Pain Management
The first-line therapy in the management of renal colic has
been parenteral administration of narcotic analgesics.
Nonsteroidal anti-inflammatory drugs (NSAIDs), however,
have assumed an increasing role in the acute management
of pain if renal function is normal. NSAIDs have been
demonstrated to reduce collecting system pressure. A
concomitant reduction in RBF induced by NSAIDs is thought
to be one of the mechanisms for decreasing collecting
Fig 1: Antegrade urinary diversion with PCN tube system pressure17. There is also a downregulation of
aquaporin water channels associated with this COX-2
The relative merits of indwelling ureteral stents and
induction, and this promotes diuresis after obstruction is
percutaneous nephrostomy tubes have been evaluated by
relieved18.
several groups. Indwelling stents obviate the need for
external collection devices but are associated with
The choice of pain management should be based on the
bothersome voiding symptoms. The choice of drainage
patient's clinical condition. NSAIDs should not be utilized in
ultimately depends on the clinical setting. If the patient has
patients with renal insufficiency as this could be
an uncorrectable coagulopathy or platelet abnormality,
exacerbated by the induced reduction in RBF. COX-1
ureteral stenting is indicated. There does not appear to be
inhibitors should not be administered to patients at risk for
a significant advantage of either approach in those
gastrointestinal bleeding or when optimal platelet
requiring drainage for stone-related problems12. 13.
function is needed.
In difficult cases where retrograde stenting is unsuccessful,

Postobstructive Diuresis
antegrade stenting can be done through PCN. Ureteral
Mechanisms
stent placement typically requires greater x-ray
After the relief of urinary tract obstruction,
exposure as compared with percutaneous nephrostomy
postobstructive diuresis may occur. Urine outputs of 200
placement13. This may be of concern in pregnant patients,
mL/hr or greater may be encountered. Although this
particularly early in gestation when the fetus is most
occurs mainly after relief of BUO or obstruction of a
sensitive to radiation effects 14. Percutaneous nephrostomy solitary kidney, it can rarely occur when there is a normal,
should be strongly considered if pyonephrosis is
contralateral kidney19. The diuresis is a normal physiologic
suspected.
response to the volume expansion and solute accumulation
occurring during obstruction. Sodium, urea, and free
Choice of Surgical Intervention
water are eliminated and the diuresis subsides after
After the acute obstruction has been relieved, definitive
solute and fluid homeostasis is achieved20.
management is planned according to the cause of
obstruction and renal functional status. Endoscopic, open,
However, a “pathologic” postobstructive diuresis may
or laparoscopic ablative and reconstructive procedures
ensue, characterized by inappropriate renal handling of
may all be utilized. A less than 10% contribution to global
water or solutes, or both. It is due to a derangement of the
renal function has been proposed as the threshold for
medullary solute gradient and a number of altered
nephrectomy. The decision for nephrectomy should be
signaling and transport pathways. It is marked by poor
made only after the affected kidney has been
responsiveness of the collecting duct to ADH.
adequately drained for a 6 to 8 weeks15. In addition, GFR
of less than 10 mL/min/1.73 m2 in the affected kidney Clinical Management of Postobstructive Diuresis
successfully predicted renal function that did not stabilize Subjects in whom BUO or UUO in a solitary kidney is
or improve after surgical correction of obstruction in relieved should be monitored for a postobstructive
diuresis. Serum electrolytes, magnesium, blood urea 8. Turkolmez S, Atasever T, Turkolmez K, Gogus O:
nitrogen (BUN), and creatinine should be monitored. This is Comparison of three different diuretic renal
a physiologic diuresis in the majority of cases that resolves scintigraphy protocols in patients with dilated
when free water and excess solutes are eliminated. Serum upper urinary tracts. Clin Nucl Med 2004;
electrolytes, BUN, magnesium, and creatinine are checked 29:154-60.
daily until the diuresis resolves. If patients have signs of 9. Smith RC, Verga M, Dalrymple N, et al: Acute
fluid overload, azotemia, or poor cognitive function or ureteral obstruction: Value of secondary signs of
hypotension, more intense monitoring should be done. The helical unenhanced CT. AJR Am J Roentgenol
clinically stable patient with good cognitive function 1996; 167:1109-13.
10. Gentle DL, Stoller ML, Jarrett TW, et al: Protease
should be given free access to oral fluids. Those with poor
inhibitor-induced urolithiasis. Urology 1997;
cognitive function should receive intravenous hydration but
50:508-11.
below the normal maintenance amounts. 11. Rothpearl A, Frager D, Subramanian A, et al: MR
urography: Technique and application. Radiology
Key Message 1995; 194:125-30.
Obstructive kidney disease is an emergency condition 12. Pearle MS, Pierce HL, Miller GL, et al: Optimal
which needs urgent evaluation and management. The method of urgent decompression of the collecting
mainstay of diagnosis of this condition is kidney function system for obstruction and infection due to
test, Ultrasound abdomen and if needed then CT Scan / ureteral calculi. J Urol 1998; 160:1260-64.
IVP. The obstruction requires immediate drainage of 13. Mokhmalji H, Braun PM, Martinez Portillo FJ, et al:
kidney in the form of either percutaneous nephrostomy Percutaneous nephrostomy versus ureteral stents
for diversion of hydronephrosis caused by stones:
(PCN) or Double J stenting. Hemodialysis is required to
A prospective, randomized clinical trial. J Urol
stabilize the patient. A combined team approach of
2001; 165:1088-92.
Urologist, Nephrologist and radiologist is highly 14. McAleer SJ, Loughlin KR: Nephrolithiasis and
recommended to treat such patients. pregnancy. Curr Opin Urol 2004; 14:123-27.
15. Kerr WS: Effect of complete ureteral obstruction
for one week on kidney function. J Appl Physiol
1954; 6:762-72.
References
16. Khalaf IM, Shokeir AA, El-Gyoushi FI, et al:
1. Laing FC, Jeffrey RB, Wing VW. Ultrasound versus
Recoverability of renal function after treatment of
excretory urography in evaluating acute flank pain.
adult patients with unilateral obstructive uropathy
Radiology 1985; 154:613-16.
2. Platt JF, Ellis JH, Rubin JM: Examination of native and normal contralateral kidney: A prospective
kidneys with duplex Doppler ultrasound. Semin study. Urology 2004; 64:664-68.
Ultrasound CT MR 1991; 12:308-18. 17. Perlmutter A, Miller L, Trimble LA, et al: Toradol, an
3. Zagoria R, Tung G: Genitourinary Radiology: The NSAID used for renal colic, decreases renal
Requisites, St. Louis: Mosby; 1997:2-6. perfusion and ureteral pressure in a canine model
4. Whitaker RH: Methods of assessing obstruction in of unilateral ureteral obstruction. J Urol 1993;
dilated ureters. Br J Urol 1973; 45:15-22. 149:926-30.
5. Ryan PC, Maher K, Hurley GD, Fitzpatrick JM: The 18. Cheng X, Zhang H, Lee H, Park JM:
Whitaker test: Experimental analysis in a canine Cyclooxygenase-2 inhibitor preserves medullary
model of partial ureteric obstruction. J Urol 1989; aquaphorin-2 expression and prevents polyuria
141:387-390. after ureteral obstruction. J Urol 2004;
6. Sperling H, Becker G, Heemann U, et al: The 172:2387-90.
Whitaker test, a useful tool in renal grafts? Urology 19. Schlossberg SM, Vaughan Jr ED: The mechanism
2000; 56:49-52. of unilateral post-obstructive diuresis. J Urol
7. Karam M, Feustel PJ, Goldfarb CR, Kogan BA: 1984; 131:534-36.
Diuretic renogram clearance half times in the 20. Loo MH, Vaughan ED: Obstructive nephropathy
diagnosis of obstructive uropathy: Effect of age and postobstructive diuresis. AUA Update Series,
and previous surgery. Nucl Med Commun 2003; Lesson 9, Vol 4, 1985.
24:797-807.

Dialysis in Kidney Disease
Dr Sanjiv Mahajan and Dr Sanjay Gupta
Introduction any of the following conditions mandates

Kidney is the only organ in the body early initiation of dialysis:
whose function can be artificially 1. Fluid overload refractory to
replaced. If damage occurs to kidneys, diuretics
the kidneys may become inefficient or 2. Hypertension poorly responsive to
may stop functioning altogether. This antihypertensive medications
process may be acute or chronic. 3. Refractory metabolic disturbances
such as hyperkalemia, metabolic
Acute Kidney Injury: An acute injury to acidosis, hypercalcemia, hypo-
kidneys can occur due to various causes calcemia, and hyperphosphatemia
such as toxins, drugs, infection or immune 4. Persistent nausea and vomiting
response. The subsequent damage is 5. Evidence of malnutrition
largely reversible if the underlying cause 6. Pericarditis or pleuritis
7. U r e m i c e n c e p h a l o p a t hy o r
is removed. However, the process may
neuropathy
take days to weeks. Hence in this period,
8. Bleeding diathesis
dialysis may be required for patient's
survival.
Renal Replacement Therapy is achieved
Indications for dialysis in the patient with
by:
acute kidney injury are: 1. Dialysis
1. Uremic complications, such as 2. Hemofiltration or
pericarditis, encephalopathy, or 3. Renal transplantation.
gastrointestinal bleeding. Dialysis is divided into two broad
2. Volume overload not treatable with categories: Hemodialysis and Peritoneal
diuretics. dialysis.
3. Severe hyperkalemia.
4. Resistant acidosis Hemodialysis
5. Acute poisoning with a dialyzable In Hemodialysis, waste products and
substance. excess water are removed extra
corporeally using an ar tificial
Chronic Kidney Disease: If an acute semipermeable membrane-dialyser.
kidney injury does not reverse, it may
progress to chronic stage. Chronic Principle
damage to kidneys also occur due to Dialysis utilizes two simple phenomenon
continuous insult from systemic diseases viz diffusion and convection for removal
such as Diabetes and Hypertension. In of waste product and excess water. The
suc h cases, the kidney function blood from the body passes over
Dr Sanjiv Mahajan
deterioates progressively. Finally, a semipermeable membranes in dialyzer
Senior Resident
stage is reached when survival is and the dialysate passes on the other
Dr Sanjay Gupta
compromised and Renal Replacement side of the semipermeable membrane.
Additional Professor
Therapy is mandated. Waste product diffuses into dialysate
Department of Nephrology
Indications for dialysis in the patient with along their concentration gradient.
All India Institute of
chronic kidney disease: Dialysate carries away the waste
Medical Sciences
In a CKD patient, dialysis is generally products and excess water, and the
New Delhi.
initiated when the estimated GFR falls cleansed blood is returned to the
below 10mL/min. However, presence of patient.
Requirements
1. Vascular access
2. Dialyser
3. Dialysate
4. Hemodialysis Machine
1. Vascular access: It is the site on the body where blood is

removed and returned during dialysis. The vascular
access should allow continuous high volumes of blood flow.
A vascular access may be temporary or permanent
a. Temporary vascular access:
I. Venous catheter: A venous catheter is placed in
jugular vein or femoral vein. In acute and emergency Fig 1: Dialyser
conditions and in non ambulatory patients, femoral
vein may be used. Otherwise, jugular vein is used "dialysate compartment." Blood is pumped via the blood
which is safer and lasts longer. Catheter in subclavian ports through this bundle of very thin capillary-like tubes
vein is now largely abandoned due to high incidence and the dialysate is pumped through the space
of stenosis. surrounding the fibers. Initial membranes were made of
ii. Arterio-venous graft: An arteriovenous graft is a cellulose. Cellulose acetate and modified cellulose
synthetic tube made of Polytetrafluoroethylene dialysers are still used. But most membranes are now
(PTFE) that is grafted between an artery and vein. made from synthetic materials, using polymers such as
The graft becomes an artificial vein that can be used polyarylethersulfone, polyamide, polyvinylpyrrolidone,
repeatedly for needle placement and blood access polycarbonate, and polyacrylonitrile. The main
during hemodialysis. A graft can be used within 2 or 3 advantage of synthetic membranes is that they activate
weeks after placement and can last several years. complement to a lesser extent than cellulose membranes.
b. Permanent vascular access:
Arterio-venous fistula (A-V fistula): It is made by joining an 3. Dialysate: It is the fluid consisting of solutes that flow
artery and a vein. Fistulas are usually made in the through the dialyser. It helps in filtering out of the toxins
nondominant arm. They are generally created on the from the blood. A typical dialysate consists of the
following sites: following composition:
· On the dorsum of the hand below the thumb - the Glucose: 200mg/dL
'snuffbox' fistula: the dorsal branch of the radial Na:140 mEq/L
artery is anastomosed to the cephalic vein. K: 1-3 mEq/L
· The forearm - Brescia-Cimino fistula: the radial artery Bicarbonate: 30-35 mEq/L
is anastomosed to the cephalic vein. Ca: 2.5 mEq/L
· The elbow-Brachiocephalic fistula: the brachial Mg: 1mEq/L
artery is anastomosed to the cephalic vein. The composition can be varied depending upon the
· A fistula takes on an average 4–6 weeks to mature. biochemical profile of the patient.
2. Dialyser: The main element in a dialyser (Fig 1) is a 4. Hemodialysis Machine: It takes care of supplying the
semipermeable membrane through which small molecules blood and the dialysate to the dialyser (fig 2). It controls
can pass by diffusion. It consists of a cylindrical bundle of the flow and the pressures and provides visual indication
hollow fibers, whose walls are composed of semi- and alarm when something goes wrong.
permeable membrane. It is then assembled into a clear
plastic cylindrical shell with four openings. One opening or The blood pump takes the blood from the patient via the
blood port at each end of the cylinder communicates with vascular access and supplies it to the dialyser. The blood is
each end of the bundle of hollow fibers. This forms the confined to the disposable plastic tubing and does not
"blood compartment" of the dialyzer. Two other ports are come in contact with any part of the machine.
cut into the side of the cylinder. These ports communicate The dialysate pump mixes the concentrate with water and
with the space around the hollow fibers and form the moves the dialysate through the dialyser.
Procedure through the space surrounding the fibers. The impurities in
See fig 3. Blood from the body is pumped through the the blood like urea diffuse to the dialysate. Pressure
plastic tubing into the dialyser. The blood pump in the gradients are applied to move fluid from the blood to the
hemodialysis machine can control the rate of blood flow. It dialysate compartment (ultrafiltration). During
is generally kept in the range of 300-450 mL/min. To ultrafiltration, the solutes in the blood also move out by
prevent clotting, it is periodically mixed with heparin. convection. The purified blood is then returned to the
body. A typical hemodialysis session lasts 4 hours and
Simultaneously, the dialysate pump mixes the concentrate needs to be repeated every 48-72 hours.
with water thus making
the dialysate of desired Hemofiltration
concentration. The The procedure of hemofiltration is somewhat similar to
dialysate is also hemodialysis but the principle involved is different. In
pumped to the dialyser hemofiltration, dialysate is not used. Solute movement
but from opposite end. with hemofiltration occurs by convection. When the blood
In the dialyser, blood flows through the dialyser, a positive hydrostatic pressure
and dialysate flow in drives water and solutes across the filter membrane. This
opposite direction filtrate is drained. The excess fluid that is drained (after
(counter current). This considering for required ultrafiltration) is replaced by an
counter current isotonic replacement fluid. The advantage of
mechanism helps to hemofiltration is that convection overcomes the reduced
m a i n t a i n t h e removal rate of larger solutes (due to their slow speed of
concentration gradient diffusion) seen in hemodialysis. Thus clearance of
along the whole length Fig 2: Hemodialysis Machine phosphate, many uremic toxins such as complement factor
of the dialyser. D, leptin, erythropoiesis inhibitors is increased.
When hemofiltration is combined with hemodialysis, the
The dialysate pump also has adjustable flow rate and it is process is known as hemodiafiltration.
typically kept in the range of 500-800 mL/min.
In the dialyser, blood is pumped through the bundle of Slow Continuous Therapies
very thin capillary like tubes and the dialysate is pumped Slow Continuous Therapies are used for hemodynamically
unstable, fluid overloaded, catabolic septic
patients. These patients are generally having
AKI or multi organ failure. The following types
of slow continuous therapies are popular.
Sustained Low-efficiency Dialysis (SLED)

In SLED, standard HD equipment is used with
reduced dialysate and blood flow rates. The
blood flow rate is kept at 100-200 mL/min
while dialysate flow rate is kept at 100 ml/min.
The session is continued for 6-10 hours.
Continuous Renal Replacement Therapy

(CRRT)
There are many variations of CRRT. They are
categorized according to the access
characteristics and also according to the
modality chosen. In Arteriovenous (AV) an
Fig 3: Hemodialysis Procedure

arterial catheter allows blood to flow into the accidental puncture. The catheter is inserted by puncturing
extracorporeal circuit by the driving force of the systemic the abdominal wall about 2.5 cm below the umbilicus in
blood pressure. The blood is returned by the venous the midline. Through the catheter, the dialysate of 1-2 L is
catheter. It does not require an extracorporeal blood introduced over a 10 minute period (inflow time). The
pump. But blood flow may be unreliable in hypotensive dialysate remains in the cavity for around 30 minutes
patients. In Venovenous (VV) both catheters are placed in (dwell time) after which it is allowed to drain over a 20
veins. An extracorporeal blood pump is required to minute period (outflow time). The cycles are then
circulate blood through the extracorporeal circuit. repeated. During acute PD, it is essential to monitor
electrolytes particularly Na and K. Potassium is generally
Irrespective of the access, any of the three modalities viz required to be supplemented after 4-8 cycles. The cycles
hemodialysis (HD), hemofiltration (H) or hemodiafiltration can be continued for 48-72 hrs after which risk of
(HDF) can be used. Thus the possible variations are peritonitis increases considerably.
CAVHD, CAVH, CAVHDF, CVVHD, CVVH and CVVHDF.
The CRRT is continued continuously for more than 48hrs till Long-term Peritoneal Dialysis
the filter clots. It is prescribed to CKD patients. It is of two main types:
Continuous Ambulatory Peritoneal Dialysis (CAPD) and
Peritoneal Dialysis Continuous Cycling Peritoneal Dialysis (CCPD).
The Peritoneal dialysis utilizes the peritoneum as the
dialyser. Peritoneal dialysis may be done acutely or The catheters inserted in both remain for many years and
chronically with different types of catheter and machines are softer and flexible. The double cuff straight Tenckhoff
but the underlying basic principle is the same. catheter, a silicone catheter, is the most commonly used
catheter. The distal (intraabdominal) segment of the
Principle catheter is positioned freely in the intraabdominal pelvic
All types of peritoneal dialysis are performed by area. The catheter's midportion is implanted within the
introducing peritoneal dialysate in the peritoneal cavity. wall of the abdomen via one to two Dacron velour cuffs.
This is achieved by inserting peritoneal dialysis catheter The deep cuff is embedded in the abdominal rectus
which permits bi-directional flow of dialysate. muscle. The superficial cuff in both double cuff and single
cuff catheters is placed subcutaneously approximately 2
The most important principle for solute removal in PD is cm from the catheter exit site on the abdominal wall.
diffusion, for which the driving force is the concentration
gradient between the blood and the dialysis fluid. Small Continuous Ambulatory Peritoneal Dialysis (CAPD)
solutes move quickly through the membrane creating an CAPD involves manual exchange of dialysate (fig 4) and
equilibrium during the dwell period. Larger solutes move
slowly across the peritoneum, reaching equilibrium point
takes a long time. Fluid removal in PD is by osmosis.
Both solute and fluid removal in PD is controlled by:
1. Glucose concentration of the dialysate
2. Dwell time of the dialysate
3. Volume of the dialysate
4. Peritoneal membrane characteristics
Types of Peritoneal Dialysis

Acute Peritoneal Dialysis
It is done for acute kidney injury. For acute peritoneal
dialysis, a short term, hard PVC catheter is used. Before
insertion, patient's bladder is emptied to prevent
Fig 4: CAPD Bag

doesn't require any machine. The patient may remain
ambulatory while the dialysate remains in the peritoneal
cavity. The fluid is allowed to stay in the abdomen for
several hours allowing excess fluid and toxins to move from
the blood to the dialysate. At the end of the dwell, the fluid
is drained by gravity into a collecting bag and the same
process is repeated. Draining dialysate and replacing it
with fresh solution takes about 30 minutes and is repeated
three to five times every day. The last exchange of the day
may be done before going to sleep, and the dialysate is
left in overnight.
Fig 5: APD Machine
Continuous Cycling Peritoneal Dialysis (CCPD) /
Automated Peritoneal Dialysis (APD) Conclusion
It uses a machine called a cycler (fig 5). A cycler circulates Dialysis is a unique modality that provides both short and
dialysate solution in and out of the peritoneal cavity at long term support for patient's survival in the absence of
evenly spaced intervals during the night for eight to 10 renal function. Type of dialysis chosen depends on various
hours. In the morning, peritoneal cavity is filled by factors such as residual renal function, co-morbidities,
dialysate that is carried in the peritoneal cavity during the hemodynamic stability, access to hospital services, work
day. During that time, patients do their daily activities. profile of the patient, physical environment and patient's
Before the patient goes to sleep, the catheter is desire. Except the transport characteristics of the
reattached to the cycler, the fluid is drained out and the peritoneum all other variables in all types of dialysis can
night exchanges are started. This cycle is repeated daily. be adjusted to achieve the desired response.
With Best Compliments From

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Kidney (Renal) Biopsy
Dr LK Jha
Kidney biopsy is one of the key invasive good pasture's disease.
procedure to determine, the cause of d. In patients with amyloidosis,
renal ailments specially nephrotic multiple myeloma or other
syndrome and AKI. Traditionally metal infiltrative disorders.
biopsy needle was used but now it has 4. Unexplained CKD: in patients with
been replaced by disposable biopsy renal dysfunction of more than 3
gun. Such performed by a trained months duration but with active
nephrologist under USG guidance, it is a urinary sediments or normal sized
safe procedure and has very few kidneys.
complications like hematoma, hematuria 5. Subnephrotic proteinuma of >1gm /
etc. day
6. Isolated hematuria – may identify
A procedure done by biopsy - needle thin basement membrane disease /
(gun) by a competent physician / surgeon Alport's / IgA nephropathy
where in strip of renal tissue is taken out 7. Familiar renal disease: eg, FSGS,
to be examined further by pathologists. Alport's disease
The needle biopsy is a specific entity as 8. Renal transplant dysfunction: In a post
opposed to surgical biopsy is which a renal transplant setting to diagnose
nephrectomised sample is provided for acute and c hronic rejection,
biopsy. recurrence of disease in transplant
kidney and drug (calcineurin
The renal biopsy is done for arriving at a inhibitors) toxicities.
diagnosis in various renal diseases and
also in classifying them. It helps in All patients have to undergo a
prognosticating about the disease and prebiopsy evaluation which includes:
also guiding us in use of treatment blood pressure control) <160/95).
modalities. · Complete hemogram with platelets
· Coagulation profile including PT,
Indications for Renal Biopsy APTT, BT, CT
1. Nephrotic syndrome: In children · USG to show that patient has two
<1yrs and in Adolescents and adult normal sized and unobstructed
with N.S. kidneys.
Also in steroids resistant nephrotics in · Urine routine and C/S
pediatric population · Check whether patient is on oral
2. AKI : In patients with unexplained AKI anticoagulants or antiplatelets and
or when there is persistent active defer renal biopsy for 4-5 days.
urinary sediments or when renal
recovery is not happening in a Procedure of Kidney Disease
patient with suspected AKI. Typically it is done as bedside
3. Systemic disease with renal procedure using ultrasound guidance
dysfunction and automated biopsy needles.
Dr LK Jha a. D i a b e t e s w i t h a t y p i c a l
Sr Consultant Nephrologist presentations: (eg. with A biopsy gun (automated needle) with
Department of Nephrology microscopic hematuria, in patient 16G or 18G needle is used. For the
Pushpanjali Crosslay Hospital where retinopathy is absent, when anxious patient, sedation may be
NCR-Delhi duration of diabetes is less than 4 needed and informed consent is taken
yrs or, when fall in GFR is rapid). from patient and relatives. An IV access
b. SLE with lupus nephritis is secured and xylocaine sensitivity
c. Systemic vacuities' - suspected testing is done before the procedure.
Wegener's granulonatosis
· The patient is allowed to lie prone
polyangiitis, polyarteritis nodosa,

Table 1: Contraindications to renal biopsy
Contraindications of Percutaneous Approach
· Uncontrolled bleeding diathesis
a. Absolute: uncorrectable bleeding diathesis
· Large volume ascites
b. Relative contraindications: Hypertension, solitary
· Uncontrolled hypertension
kidney, multiple renal cysts, renal neoplasm, advanced · Morbid obesity
azotemia obesity, pyelonephritis kidney, uncooperative · Severe respiratory insufficiency
patient. Wherever possible above parameters should · Solitary kidney
be corrected before undertaking biopsy. · Failed percutaneous approach
patients with stable vitals may be discharged after day
with pillow under the abdomen to splint the kidneys. care admission.
· Ultrasound is used to localize the lower pole of kidney
preferably left kidney (as it is longer) and the site is Transjugular or transfemoral renal biopsy is rarely done
marked with pen. when a percutaneous approach is contraindicated. Other
· The skin is prepared and local anasethetic 2%, routes are open surgical renal biopsy and laparoscopic
xylocaine) is injected till the depth of the capsue of renal biopsy.
kidney. A help of lumber puncture needle (22-24G)
may be needed. Complications
· A small stab incision (2-3mm) followed by passage of In large series of renal biopsies
biopsy gun is made under USG guidance till capsule 1. Hematoma 3% - Clinically significant
of the kidney. 2. Gross hematuria 3%
· Patient is then told to take deep breath and hold 3. AV fistula formation 0.2% - by contrast enhanced
breath for 5-10 seconds and the automated needle is studies 15%
triggered on. The biopsy needle is withdrawn 4. Need of surgery < 0.1%
immediately. (nephrectomy) < 0.05%
· The above procedure is repeated – 2nd core is also 5. Death
taken from same site. 6 Biopsy of other organ by mistake
· The samples are sent to laboratories in different 7. Pneumothorax
preservatives for histopathology (formalin) for 8. Hemothorax
immunofluorescence (saline) and for 9. Page kidney - perirenal hematoma compressing upon
electronmicroscopy (glutargldehyde). kidney leading to renin mediated HTN
· If insufficient material is obtained further passes of
needle can be made.
Though above is the standard procedure, there may be

operator based accepted variations - like use of
ultrasound for location of the kidney and then performing
it without real time guidance.
· A CT guided procedure is also done in specific
circumstance.
· The biopsy is transplanted kidney is generally easier
as it is more superficial and generally immovable. The
general technique remains same.
Post Biopsy
Following the biopsy patient is rested in supine position for
at least 6-8 hrs.
· The staff is instructed to monitor vitals frequently and
notify any discrepancy.
· The patient is given separate containers of clear glass
for collecting urine for observing any gross hematuria.
· In the absence of hematuria patient is allowed to sit in
bed after 8 hrs and to gradually ambulate. Patient is
not allowed to sit or walk till hematuria is cleared.
Traditionally patients are kept overnight in hospital after

biopsy but lately after uncomplicated biopsy and

Stem Cell Therapy in Nephrology
OL Kukharchuk, VV Radchenko, AB Padma Priya,
AO Kukharchuk and Pranav Anam
What are stem cells? process of treatment is to inject the

Stem cells have three main prepared stem cells into a patient to
characteristics. First – they are not repair specific tissues or to grow organs.
specialized cells (in contrary to cells of
muscles, brain, or heart). Second – stem Can we treat renal diseases with stem
cells are capable to divide significantly cells?
more number of times, than usual cells. To decide the issue of possibility of using
While dividing stem cells self-renews: stem cells in treatment of renal diseases,
one among the 2 formed cells becomes at the foremost needed to answer the
differentiated, and the second remains question – do stem cells exist in the renal
the stem cell. The third important tissue of the adult organism, which are
characteristic of stem cells is their ability capable to differentiate into highly
after division to differentiate into specialized cells of the kidneys
specialized cells, like muscle cells, brain structural-functional units – nephrons? If
cells, blood cells and others. Cells of 1- stem cells exist in kidneys, this means that
day embryo can differentiate into any of in renal tissue occurs process of
240 types of cells. In adult organism physiological and reparative
small amount of stem cells is present in all regeneration on which we could
organs, providing the reparation influence with the help of stem cells
(restoration) of injures and damaged transplantation. Recent results obtained
tissues. The younger the organism is the in humans. Suggest that the kidney
bigger stem cell reserve is, and contains a “renopoietic system”, with a
accordingly body's restoration potential. progenitor localized at the urinary pole
It is considered that application of stem of Bowman's capsule, from where it can
cells in medicine will give the possibility initiate the replacement and
to successfully combat diseases that are regeneration of glomerular, as well as
regarded incurable today. tubular, epithelial cells (Fig. 1)1.
What is stem cell therapy? Thus, renal stem/progenitor cells might

Cell therapy (cell transplantation) is a contribute to tubular epithelium repair,
treatment with stem cells and tissues and but this contribution probably occurs only
also with biologically active substances when a renal tubular injury cannot be
they produce. Cell therapy is a branch of spontaneously repaired through the
modern medicine studying stem cells and migration of neighboring unwounded
OL Kukharchuk
their clinical use. The main indication for tubular cells.
VV Radchenko
stem cell therapy is disease or condition
AB Padma Priya
resulting in cell count reduction. Stem cell How the regeneration process changes
AO Kukharchuk treatments are a type of regenerative in renal diseases?
Pranav Anam medicine that introduces new cells into Most renal pathological conditions that
damaged tissue in order to treat a ultimately lead to end-stage renal
disease or injury. Over 70 different disease (ESRD), originate within the
disorders have been identified as glomerulus, and it has now been
amenable to stem cell therapy. The established that depletion of podocytes,

Fig 1: Series of schematic diagrams depicting the
morphological events and the localization of
CD24+CD133+ renal progenitors during the
different phases of nephron development1
Mesenchymal cells near the tips of the branching
ureteric bud are induced and differentiate
through a series of forms: aggregate (A), renal
vesicle (B), comma-shaped bodies (C), and S-
shaped bodies (D). Also shown is the developing
vasculature within the glomerular cleft of an S-
shaped body (E) and the glomerulus in a more
mature nephron (F). The tubular segments of the
mature nephrons empty into the collecting ducts
and eventually the ureter. Development proceeds
in a radial manner so that older nephrons are
centrally located and newer nephrons are added
at the periphery as indicated. Cells of the ureteric
bud are stained in green. CD24+CD133+ renal
progenitors are stained in red. (A):
CD24+CD133+ renal progenitors (red) localize
in the condensed mesenchyme but not in the
uninduced mesenchyme (white) or in the ureteric
bud (green). (B): CD24+CD133+ renal
progenitors localize in a primary vesicle but not in
the uninduced mesenchyme (white) or in the
the visceral epithelium of the capillary tuft, is central in ureteric bud (green). (C): CD24+CD133+ renal
initiation of glomerulosclerosis, which is the common final progenitors localize in the comma bodies but not in
pathway of all glomerular diseases leading to ESRD. In the uninduced mesenchyme (white) or in the
glomerular diseases such as diabetic nephropathy, ureteric bud (green). (D): CD24+CD133+ renal
glomerulonephritis, or preeclampsia, significant numbers progenitors localize in the S-shaped body, in the
of podocytes are lost as a result of apoptosis, necrosis, or proximal loop, as well as in the distal loop, but not
in the uninduced mesenchyme (white) or in the
excretion of living cells into the urine. Unlike tubular cells,
ureteric bud (green). (E): CD24+CD133+ renal
podocytes are postmitotic cells that cannot undergo
progenitors (red) localize in an S-shaped body
complete cell division and are therefore unable to
after colonization by primordial capillaries and
regenerate themselves. Remission of disease and
mesangium. (F): In maturing glomeruli,
regression of renal lesions are widely observed in
CD24+CD133+ renal progenitors (red)
experimental animals and even in humans. However, the
selectively persist as a subset of cells of the
repair of injured renal tissue in mammals is not sustained
Bowman's capsule localized opposite to the
by the generation of new nephrons and frequently leads
vascular pole.
to a nonfunctioning mass of fibrotic tissue. In contrast,
early in gestation, injured fetal tissues can be completely
recreated, without fibrosis, in a process resembling properties also exist in adult mammalian kidneys. Adult
regeneration. renal progenitors are localized at the urinary pole of
Bowman's capsule, the only place of the nephron from
How does the adult kidney replenish cells lost through where they can initiate the replacement and regeneration
damage or aging? of glomerular, as well as tubular, epithelial cells. Thus,
Recent results demonstrate that, during development, converging evidence suggests that the kidney contains a
mammalian nephrons derive from a single multipotent renopoietic system and that the urinary pole of Bowman's
progenitor that generates glomerular as well as tubular capsule may represent a stem cell niche, which is a specific
epithelial cells and those cells with identical markers and site in adult tissues where stem cells reside2.
Which stem cells are needed to be used in renal master stem cell in the kidney that can recapitulate
diseases and where must be introduced? development.
The question of which cell type is required is not a simple
one to answer for an organ such as the kidney, and the Could transplantation of mesenchymal stem cells
answer may well vary depending on the renal disease. restore the renal function?
The nexus between glomerular and tubular function and Transplantation of bone marrow mesenchymal stem cells
disease is a close one, and it has been debated as to (BM-MSC) from rodents has been identified as a strategy
whether nephron loss results from glomerular injury or for renal repair in experimental models of acute kidney
from tubule-interstitial responses. It has been argued that injury (AKI), a highly life-threatening clinical setting. The
the survival of a nephron after damage depends on the therapeutic potential of BM-MSC of human origin has not
ongoing health of the glomerulus, rather than the tubule been reported so far. Morigi M. et al. investigated
itself. This observation is consistent with the proposed whether human BM-MSC treatment could prevent AKI
notion of Bowman's capsule progenitor cells2. What is induced by cisplatin and prolong survival in an
clear is that, whether replacement of cells within existing immunodeficient mouse model. Results showed that human
nephrons or loss of those nephrons followed by interstitial BM-MSC infusion decreased proximal tubular epithelial
fibrosis, no new nephrons arise. In the case of cell injury and ameliorated the deficit in renal function,
mesenc hymal stem cells, these cells are not resulting in reduced recipient mortality. Infused BM-MSC
transdifferentiating but rather provide a reparative became localized predominantly in peritubular areas
cytokine/chemokine environment. The longevity of these and acted to reduce renal cell apoptosis and to increase
positive effects vs the potential for long-term damage proliferation. BM-MSC also induced protection against
resulting from the aberrant differentiation of MSCs AKI-related peritubular capillary changes consisting of
remains unclear. If both of these concerns are allayed, endothelial cell abnormalities, leukocyte infiltration, and
then the delivery of such “support cells” may prove a low endothelial cell and lumen volume density as assessed
viable treatment without the need for a renal stem cell. If by morphometric analysis. These findings indicate that
stem, renal, or non-renal cells are to be delivered into this human MSC of bone marrow origin hold potential to
complex solid organ, then they will have to be injected into prolong survival in AKI and should be considered for
the parenchyma or bloodstream. Delivery of cells through testing in a clinical trial4.
the systemic circulation results in entrapment, particularly
within the pulmonary microvasculature. An active homing The Kunter U et al study sought to determine whether
mechanism may also be required for introduced cells to intrarenal injection of rat mesenchymal stem cells (MSC)
preferentially reach the kidney. Some studies showed cells can preserve renal function in a progressive rat model of
introduced into the circulation do reach the kidney – either glomerulonephritis (GN). Early in GN (day 10),
by homing or passive transfer – and integrate into the fluorescently labeled rat MSC localized to more than
parenchyma3. Delivery of cells directly into the renal 70% of glomeruli, ameliorated acute renal failure, and
parenchyma would deliver cells only into restricted reduced glomerular adhesions. Fifty days later,
regions of the kidney. proteinuria had progressed in controls to 40±25 mg/d
but stayed low in MSC-treated rats (13±4 mg/d; P <
Is it possible the renal structures to restore? 0.01). Renal function on day 60 in the MSC group was
Even if these cells proliferated and integrated locally, better than in medium controls. Kidneys of the MSC group
global organ-wide integration is unlikely. With a greater as compared with controls on day 60 contained 11%
understanding of normal cellular turnover within the more glomeruli per 1-mm2 section of cortex but also
kidney, whether involving resident progenitor/stem cells significantly more collagen types I, III, and IV and α-
or an exogenous cell homing to the kidney, the more smooth muscle actin. Approximately 20% of the glomeruli
feasible scenario may be to re-stimulate this response in of MSC-treated rats contained single or clusters of large
situ rather than have to deliver the cells themselves. adipocytes with pronounced surrounding fibrosis.
Current evidence supports a greater capacity for the Adipocytes exhibited fluorescence in their cytoplasm
kidney to repair in response to damage than once and/or intracellular lipid droplets. Lipid composition in
appreciated, including evidence for progenitors of these adipocytes in vivo mirrored that of MSC that
specific cell types; however, there is no evidence for one underwent adipogenic differentiation in vitro. Thus, in this

GN model, the early beneficial effect of MSC of pulmonary disease, and age 65 years. Preliminary
preserving damaged glomeruli and maintaining renal analysis of the outcomes in this cohort of study subjects
function was offset by a long-term partial mal showed that the suprarenal, postoperative administration
differentiation of intraglomerular MSC into adipocytes of allogeneic MSCs is feasible and safe, as it has not
accompanied by glomerular sclerosis. These data suggest resulted in adverse or serious adverse events, and
that MSC treatment can be a valuable therapeutic preliminary efficacy data appear promising, showing,
approach only if adipogenic mal differentiation is compared with well-matched historical case controls from
prevented5. the same institution, that MSC therapy prevented
postoperative deterioration in renal function, reduced
Could transplantation of hematopoietic stem cells length of stay, need for readmission, and prevented late
restore renal function? deterioration in renal function7.
Li B et al studied the capacity of human CD34+
hematopoietic stem/progenitor cells (HSPCs) to promote Could it be effective stem cells transplantation in
kidney repair and regeneration using an established chronic kidney disease?
ischemia/reperfusion injury model in mice, with particular End-stage renal disease is defined as the inability of the
focus on the microvasculature. Human HSPCs administered kidneys to remove waste products and excess fluid from
systemically 24 hours after kidney injury were selectively the blood. ESRD progresses from earlier stages of chronic
recruited to injured kidneys of immunodeficient mice and kidney disease (CKD) and occurs when the glomerular
localized prominently in and around vasculature. This filtration rate is below 15 ml/minute/1.73 m2. CKD and
recruitment was associated with enhanced repair of the ESRD are dramatically rising due to increasing aging
kidney microvasculature, tubule epithelial cells, enhanced population, population demographics, and the growing
functional recovery, and increased survival. HSPCs rate of diabetes and hypertension. Identification of
recruited to kidney expressed markers consistent with multipotential stem/progenitor populations in mammalian
circulating endothelial progenitors and synthesized high tissues is important for therapeutic applications and for
levels of pro-angiogenic cytokines, which promoted understanding developmental processes and tissue
proliferation of both endothelial and epithelial cells. homeostasis. Progenitor populations are ideal targets for
Although purified HSPCs acquired endothelial progenitor gene therapy, cell transplantation, and tissue engineering.
marker since recruited to the kidney, engraftment of The demand for kidney progenitors is increasing due to
human endothelial cells in the mouse capillary was an severe short age of donor organs. Because dialysis and
extremely rare event, indicating that human stem cell transplantation are currently the only successful therapies
mediated renal repair is by paracrine mechanisms rather for ESRD, cell therapy offers an alternative approach for
than replacement of vasculature. These studies advance kidney diseases. However, this approach may be relevant
human HSPCs as a promising therapeutic strategy for only in earlier stages of CKD, when kidney function and
promoting renal repair after injury6. histology are still preserved, allowing for the integration
of cells and/or for their paracrine effects, but not when
What are the clinical trials efficacy of stem cells have small and fibrotic end-stage kidneys develop. Although
been performed in humans? blood- and bone marrow-derived stem cells hold a
Westenfelder Ch, Togel FE conveys about the results of therapeutic promise, they are devoid of nephrogenic
Phase I Clinical Trial, in which allogeneic MSCs were potential, emphasizing the need to seek kidney stem cells
administered to patients who were at high risk for open- beyond known extra renal sources. Moreover,
heart surgery-associated AKI. In this safety and feasibility controversies regarding the existence of a true adult
trial, adult subjects who have undergone on-pump kidney stem cell highlight the importance of studying cell-
coronary artery bypass graft and/or cardiac valve based therapies using pluripotent cells, progenitor cells
surgery were infused via the suprarenal aorta with from fetal kidney, or dedifferentiated/reprogrammed
allogeneic MSCs, using a dose-escalating protocol. All adult kidney cells8.
studied subjects presented with the following risk factors
for post-cardiac surgery-associated AKI: under lying Could fetal stem cells transplantation restore function
chronic kidney disease-1 to 4, congestive heart failure, of kidney?
diabetes mellitus, hypertension, chronic obstructive As nephrogenesis progresses the relative proportion of

the nephrogenic zone decreases. However, due to the fact
that stem cells are present in the fetal kidney until
relatively late in gestation term, can be exploited for their
isolation, making the fetal kidney an attractive source for
isolation and utilization of tissue-specific stem cells.
Encouraging results regarding the use of cells from
developing kidneys came from a report demonstrating
that transplantation of a heterogeneous population of
dissociated E14.5 and E17.5 rat fetal kidney cells under
the kidney capsule lead to the creation of renal structures,
and had beneficial effects on kidney function in a 5/6
nephrectomy model of kidney injury9. Also showed that
similarly to whole organ transplants, the gestational age
of cells to be transplanted has to be chosen carefully, as
early fetal kidney (E14.5) cells differentiated to non-
renal tissues, whereas cells from later gestational stages
showed poor ability to form kidney structures. Kim et al10
recently showed that E17.5 rat fetal kidney cells were
able to reconstitute kidney tissues only when cultured
through passage one, whereas P2 cells experienced
proliferation arrest and apoptosis, leading to poor
regenerative potential in vivo.
Do results exist on treating renal diseases in humans

with the help of fetal stem cells?
Tissues of fetal kidney consists all cellular elements in
developmental stages, which has potential to replace
damaged (injured) renal structures in adults (Fig. 2)2.
Results of the clinical trials, performed in Ukraine,
Fig 2: Stem cells in fetal kidney2
evidences that in cases of sustaining not less than 50% of
renal parenchyme the transplantation of fetal stem cells, From 12-13 and till 18-20 weeks of human gestation:
performed on the background of hemodialysis, in chronic (a–b) localization of SIX2 to the MM, predominantly to the
renal insufficiency reduces the level of creatinine in blood CM.
(c–d) shaped bodies and renal stroma.
plasma, increases glomerular filtration, normalize the (e–f) nephrogenic zone and newly forming tubules.
capability of kidney to concentrate urea. In 63% of (g–h) nephrogenic cortex, parietal epithelium of fetal
patients renal functions restores, that allows to eliminate glomeruli.
(i–j) some differentiated tubules.
from further hemodialysis (Fig. 3).
Conclusion
Until recently, basic paradigm of nephrology was that
kidneys are not capable to regenerate, but restoration
function of kidney occurs exclusively due to hypertrophy
of undamaged nephrons. Today we are aware that renal
tissues are like neural cells, restores due to division of
adult stem cells which are located in renal parenchyme.
These cells could be stimulated for division and
differentiation by introducing mesenchymal or
hematopoietic stem cells to patient. Therefore, the most
effective treatment of nephrological diseases could be
the stem/progenitor cells of fetal kidney. Fig 3: Dynamic of kidney function after SCT

Nutrition in Renal Failure
Charu Dua
A high prevalence of malnutrition exists eating habits have been investigated,
in patients with renal failure. Several and the patient demonstrates a clear
surveys have reported protein-calorie need for dietary restriction.
malnutrition in up to 40% of this patient
population(1,2). Malnutrition in renal Moreover Indian scenario is totally
failure is multifactorial, but surveys different than American scenario,
consistently report inadequate oral where protein restriction needs to be
intake as a major contributing factor (1, 2). imposed. Most of the Indian who are
Indicators of nutrition status including vegetarian do eat anywhere between
reduced nutrient intake and muscle mass 0.6gm – 0.8 gms of protein/ Kg
are each independently associated with Bodyweight. If this population is
increased 12-month mortality ( 2 ) . asked further to reduce protein in diet it
Gastrointestinal complaints are will gradually push them towards
frequently seen in this patient population malnutrition. Most of the CKD patients
and likely contribute to decreased intake seen in dietary OPD/IPD are almost on
and malnutrition(3–5). Research suggests negligible protein diets, which push
that addressing GI issues in patients with them closer towards malnutrition.
renal failure may improve nutritional
status ( 5 ) .Although the traditional Furthermore, underlying causes for
surrogate markers of malnutrition, such electrolyte abnormalities such as poor
as decreased muscle mass or serum glucose control, use of potassium
proteins have been associated with c o n t a i n i n g s a l t - s u b s t i t u t e s, o r
increased mortality, research is ongoing medications as a cause of hyperkalemia
to determine if improving nutritional should be addressed before imposing
status will alter patient outcomes. diet restrictions.
Decreased muscle mass or serum proteins This article is written with an intention
can also be attributed to activation of the that will empower the patients and
acute-phase response related to co- physicians to make better choices.
morbid conditions. However, there are
several studies that demonstrate that the Nutrition in Chronic Kidney Failure
provision of increased nutrition to (CKD) for adults
patients with malnutrition and renal Healthy kidney takes out the waste
failure may improve patient outcomes (1, 6). products and extra minerals from foods
eaten. They maintain
Mrs Charu Dua
Overzealous diet restrictions can also · Sodium and water balance
HOD – Dietetics,
contribute to decreased intake. The · Support normal bone health by
Nutrition & F&B
provision of a “renal diet” that limits balancing calcium and phosphorous
Pushpanjali Crosslay Hospital
protein, salt, potassium, phosphorus and
NCR-Delhi
fluid may further limit intake in a patient When your kidneys are not working
with existing malnutrition and poor oral properly, they cannot get rid of waste
intake. Dietary intervention should not be products and extra fluids. CKD usually
instituted until nutritional status and takes a long time to develop and does
December 2012
not go away. In CKD, the kidneys continue to work — just Food Item Protein Content (gms)
not as well as they should. Wastes may build up so
Milk ( 250ml) 8 gms
gradually that the body becomes used to having those
Curd ( 100gms) 4.2 gms
wastes in the blood. Minerals in food such as potassium, Paneer ( 40gms) 10gms
sodium and phosphorous accumulate in your body and put Egg White 5 – 6 gms
the heart, bones, lungs and general health at risk. Chicken/ Fish (50gms) 12 – 13 gms
Generally people are at risk for developing CKD because Dals/ Besan/ Sprouts/ Soya 7 gms
they have diabetes, high blood pressure, or both. High ( 1 Medium Size Katorie,
blood glucose levels put people with diabetes at risk for 30 gms raw)
heart disease, stroke, amputation, and eye and kidney
problems. People with high blood pressure are at risk for Seek help of a dietician to know how protein is good for
damaged blood vessels, including tiny vessels in the you, and how you can balance the intake and taste, while
kidneys. helping kidneys to heal.
2) Potassium: is primarily present in vegetables and fruits,

The goal of diet is to focus on
Salads, Fruit Juices , soups, lime, Coconut water, Dried fruits
· Preventing the excess accumulation of fluids and
, nuts, tomato chutney, coconut Chutney etc If it begins to
wastes, while allowing the kidney to heal.
climb (check vis blood test), talk with your dietitian about
· To control and maintain blood glucose levels ways to limit the amount of potassium you eat. You may
· To control blood pressure need to avoid some fruits and vegetables. You can reduce
· To regulate your intake of Proteins, Potassium, the potassium content of food by following the tips below:
Phosphorous, Sodium (salt), Calcium, Fluid Intake. a. Dialyzing potatoes and other vegetables - you can
remove some of the potassium from potatoes and
Do's and Don'ts of Diet other vegetables by peeling them, then soaking them
1) Proteins: Protein is an essential part of any diet. in large amount of water for several hours before use.
Proteins help build and maintain muscle, bone, skin, b. Drain and rinse well before cooking
connective tissue, internal organs, and blood. They help c. Cooking all the vegetables helps removing some
fight disease and heal wounds. But proteins also break potassium. Hence you may use tomatoes while
down into waste products that must be cleaned from the cooking, avoid them raw. Remember food has to be
blood by the kidneys. Eating more protein than your body tasty as your disease is making you anorexic (feeling
needs may put an extra burden on the kidneys and cause less hungry)
kidney function to decline faster. d. Avoid taking too much raw salad.
Doctors have long recommended that patients with CKD e. Limiting potassium content by portion control (the
eat moderate or reduced amounts of protein. amount of a food that you eat at one time) for e.g. a
high potassium tomato (1 small) provides 273 mg of
Some patients, however restrict or totally avoid proteins potassium. If you cut a thin slice to accent your
that leads to malnutrition( body is using muscle for energy) sandwich it provides much less; 1/6th of 1 small
Indian population is mostly vegetarian, and is already on tomato provides 45 mg of potassium.
a low protein diet, before reducing protein in your diet f. Food Rich in potassium are Bananas, Oranges, melons,
seek advice of a dietician the recommended amount of excess tomatoes, raw vegetables, lemon, alma ,
protein intake should be 0.8gms/KG/BW. So if you ways vegetable soups, mushrooms, arbi, kathal chutneys
60kgs you should take atleast 48gms of protein in your coconut water, fruit / vegetable juices etc.
diet. Also it is important to take high biological value g. Fruits that are low in potassium are apples,
quality proteins (good quality protein like milk, paneer, pineapple, papaya, guava. Still remember not to
egg, soya, chicken, fish etc). Though theses protein take more 100gms a day even if your potassium are
increase the urea levels a balance of both good quality normal seek help of a dietician to know more.
and bad quality protein (dals, rice, wheat etc) is important 3) Sodium: Sodium is found in ordinary table salt and
to maintain. Know the protein values many salty seasonings like soy sauce etc. Canned foods,
December 2012
some frozen foods, and most processed foods have large contains water. These foods include tea, coffee, soups,
amounts of table salt. Snack foods like chips and namkeens melons, grapes, oranges, tomatoes, dals curd, milk,
are also high in salt. Too much sodium in your diet can be lassi, jelly lettuce and celery. All these foods add to
harmful because it causes your blood to hold fluid. The your fluid intake.
extra fluid raises your blood pressure and puts a strain on
your heart and kidneys. Talk with your dietitian about ways 6) Diabetes and Kidney Disease:
to reduce the amount of sodium in your diet. · Eat 5 -6 small Frequent Meal
· Look for the sodium content on the nutrition labels of · Do Not Skip Meals. Keep day to day intake consistent
the foods you buy. Choose "sodium-free" or "low- so that the medication regime matches the food
sodium" food products. Aim to keep your daily intake Eat meals and snacks at the same time each
sodium intake less than 1,500 milligrams. day to prevent high/low blood sugar levels.
· Try alternative seasonings like imli juice, salt-free · Use snacks to prevent severe hypoglycemia. Be sure
seasoning mixes, or herbs like ( oregano, basil, to have a bedtime snack containing protein, starch,
thyme, roasted zeera, black pepper ) fat to provide the body with an energy source that
· Avoid salt shaker on the table, chaat masala, metha will last through the night.
soda, aji-no-motto (MSG) · Manage carbohydrate intake carefully since the
amount of carbohydrate eaten, the time it was eaten
4) Phosphorus: is a mineral found in many foods. Too much and what it was eaten with determines the blood
phosphorus in your blood pulls calcium from your bones. sugar level.
Losing calcium will make your bones weak and likely to · Avoid over- treating low blood sugar by eating
break. Too much phosphorus may also make your skin itch. enough carbohydrates to raise blood sugar.
Foods like milk and cheese, dried beans, peas, colas, Checking blood sugar every 10mins will help
canned iced teas and lemonade, nuts, few chocolates and determine how much to eat.
peanut butter are high in phosphorus. Talk with your · Reduce cholesterol and saturated fat intake: reduce
dietitian about how much phosphorus you should have in total fat and trans fatty acid intake
your diet. As your kidney disease progresses, you may · Maintain appropriate weight for height: avoid
need to take a phosphate binder(your doctor may becoming overweight.
prescribe) These medications act like sponges to soak up, · Increase fiber intake (Salads, Sprouts, vegetables,
or bind, phosphorus while it is in the stomach. Because it is fruits, brown bread, oats etc)
bound, the phosphorus does not get into the blood. Instead, · Avoid foods high in salt ( Processed food, canned
it is passed out of the body in the stool. food, market butter, ketchups, sauces, salt shaker etc)
· Avoid excessive protein intake by eating less red
5) Water: As your kidney disease progresses, you may meat.
need to limit how much you drink because your kidneys · Avoid Eating Sugar and Its products
cannot remove the extra fluid, so it builds up in your body · Avoid eating fruits with Main Meals, eat them in
and strains the heart. Tell your doctor if you notice you are between. Avoid fruits like mango, banana, cheeku,
making either less urine or more urine or if you have any grapes if your sugars are high. Avoid fruit juices (
swelling around your eyes or in your legs, arms, or fresh or tetra pack)
abdomen. If your doctor has asked you to reduce fluid/ · Avoid eating vegetables like potatoes, arbi, sweet
water intake then follow the below potato
· Drink water as per thirst, don't take in excess. Drink sip
by sip do not gulp 7) Hypertension and Kidney Disease:
· You can keep fluids down by drinking in small cups or High Blood Pressure (hypertension) is a strong risk factor
glasses. for heart disease, stroke and kidney failure. Most patients
· Freeze juices in an ice cube tray and eat it like a candy with established hypertension do not make sufficient
or a bar. life–style changes, do not take medicines and neglect
· Plan one day of your fluid serving at every meal their disease. Therefore to prevent and control
· Any food that is liquid at room temperature also hypertension one needs to undergo lifestyle modification.
December 2012
Lifestyle modification not only improves control but also dialysis sessions, causing swelling and weight gain.
helps to reduce medication doses in hypertension. The extra fluid affects your blood pressure and can
Moreover, they help in preventing high blood pressure. make your heart work harder. You could have serious
heart trouble from overloading your system with
Lifestyle Modifications for Hypertension Prevention fluid.
and Management Control your thirst
Here are some tips on healthy living and lifestyle · The best way to reduce fluid intake is to reduce
modifications that would be helpful to everyone in the thirst caused by the salt you eat. Avoid salty foods
family along with the person with high blood pressure. So like chips etc. Choose low-sodium products.
these should be adopted by all and no separate cooking · You can keep your fluids down by drinking from
for the patient. smaller cups or glasses. The dietitian will be able
· Lose weight if overweight – Eat to live, do not live to to give you other tips for managing your thirst.
Eat. Your dry weight is your weight after a dialysis session
· Regular Physical Activity – Wise depend on Exercise when all of the extra fluid in your body has been
for fitness. removed. If you let too much fluid build up between
· Reduce intake of dietary saturated fat - Clean up the sessions, it is harder to get down to your proper dry
oily mess. weight. Your dry weight may change over a period
· Reduce salt (sodium) intake – Excess Salt is harmful. of 3 to 6 weeks. Talk with your doctor regularly
· Maintain adequate intake of dietary potassium –
about what your dry weight should be.
Diet rich in fruits and vegetables. 2. Continue to restrict potassium/ Phosphorous. One
· Limit intake of alcohol – There is a Devil in Every Berry
fruit during dialysis is still okay but do not take more.
of Grape. Try not to take fruits with high water con tenet (
melons, oranges etc)
· High dietary fiber intake – He who follows nature is
3. Protein: Before when you were not on dialysis, your
never out of the way.
doctor may have told you to follow a low-protein
· Avoid smoking and intake of excess caffeine – Don't
diet. Being on dialysis changes this. Most people on
get reduced to ashes.
dialysis are encouraged to eat as much high-quality
protein as they can. Protein helps you keep muscle
Nutrition during dialysis
and repair tissue. The better nourished you are, the
When you start dialysis, you must make many changes in
healthier you will be. You will also have greater
your life. Watching the foods you eat will make you
resistance to infection and recover from surgery
healthier. Food gives you energy and helps your body
more quickly. Your body breaks protein down into a
repair itself. Food is broken down in your stomach and
waste product called urea. If urea builds up in your
intestines. Your blood picks up nutrients from the digested
blood, it's a sign you have become very sick. Eating
food and carries them to all your body cells. These cells
mostly high-quality proteins is important because
take nutrients from your blood and put waste products
they produce less waste than others. High-quality
back into the bloodstream. When your kidneys were proteins come from meat, fish, milk, poultry, and eggs
healthy, they worked around the clock to remove wastes (especially egg whites). Seek help from Dietician to
from your blood. The wastes left your body when you know the amount of protein you can now have in your
urinated. Other wastes are removed in bowel movements. diet.
4. Sodium: Sodium is found in salt and other foods.
Now that your kidneys have stopped working, dialysis Most canned foods and frozen foods contain large
removes wastes from your blood. But between dialysis amounts of sodium. Too much sodium makes you
sessions, wastes can build up in your blood and make you thirsty. But if you drink more fluid, your heart has to
sick. You can reduce the amount of wastes by watching work harder to pump the fluid through your body.
what you eat and drink. A good meal plan can improve Over time, this can cause high blood pressure and
your dialysis and your health. congestive heart failure.
1. Fluids: You continue to restrict fluid as advised by Try to eat fresh foods that are naturally low in sodium
your doctor/ dietician. Fluid can build up between Look for products labeled low sodium.
December 2012
Talk with a dietitian about spices you can use to flavor
your food. The dietitian can help you find spice blends 7. Mehrotra R, Kopple JD, Wolfson M. Metabolic
acidosis in maintenance dialysis patients: clinical
without sodium. considerations. Kidney Int Supp,2003;( 88): S13-
S25.
8. Mitch WE, Price SR. Mechanisms activating
References proteolysis to cause muscle atrophy in catabolic
1. Mehrotra R, Kopple JD. Nutritional management of conditions. J Ren Nutr, 2003; 13( 2):149- 152.
maintenance dialysis patients: why aren't we doing
9. Natl. Kidney Found. I Init. K-DOQ. Clinical practice
better? Ann Rev Nutr,2001; 21: 343- 379.
guidelines for nutrition in chronic renal failure. Am J
2. Kopple JD. Pathophysiology of protein-energy
Kidney Dis, 2000; 35:S1-S140.
wasting in chronic renal failure. J Nutr, 1999;129(1S
Suppl):247S-251S. 10. Bergstrom J, Furst P, Alvestrand A, et al. Protein and
3. Strid H, Simren M, Stotzer P, et al. Patients with energy intake, nitrogen balance, and nitrogen
chronic renal failure have abnormal small intestinal losses in patients treated with continuous
motility and a high prevalence of small intestinal ambulatory peritoneal dialysis. Kidney Int,
bacterial overgrowth. Digestion, 2003;67(3):129- 1993;44: 1048- 1057.
137. 11. Walser M, Mitch WE, Maroni BJ, Kopple JD. Should
4. Van Vlem B, Schoonjans R, Vanholder R, et al. protein intake be restricted in predialysis patients?
Delayed gastric emptying in dyspeptic chronic Kidney Int,1999; 55( 3): 771- 777.
hemodialysis patients. Am J Kidney Dis, 2000; 36( 5): 12. Ikizler TA, Pupim LB, Brouillette JR, et al.
962- 968. Hemodialysis stimulates muscle and whole body
5. Ross EA, Koo LC. Improved nutrition after the protein loss and alters substrate oxidation. Am J
detection and treatment of occult gastroparesis in Physiol Endocrinol Metab, 2002; 282:E107-E116.
nondiabetic dialysis patients. Am J Kidney Dis, 1998; 13. Scheinkestel CD, Kar L, Marshall K, Bailey M,
31(1): 62- 66. Davies A, NyulasiI, Tuxen DV. Prospective
6. Capelli JP, Kushner H, Camiscioli TC, Chen SM, Torres randomized trial to assess caloric andprotein
MA. Effect of intradialytic parenteral nutrition on needs of critically ill, anuric, ventilated patients
mortality rates in endstage renal disease care. Am J requiring continuous renal replacement therapy.
Kidney Dis, 1994; 23(6): 808- 816. Nutrition, 2003; 19(11-12): 909- 16.
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December 2012
Mildly Elevated Transaminases (ALT, AST) :
Why And What To Do
Dr Vibhu V Mittal
Abstract Some of the recent studies have pointed
Mildly elevated transaminase is seen in the need to lower the values of "normal"
upto 1-9% of population. It signifies ALT to 19 U/L for male and 30 U/L for
ongoing liver injury. There are varied female to increase the sensitivity of
common and uncommon hepatic and diagnosing cases of mild hepatitis.
extrahepatic causes for this. Evidence Though at these levels the specificity is
regarding the corect approach of compromised with increase in number of
evaluation is limited and the expert incidental abnormalities.
consensus is for step based approach for
this problem. Detailed history and Anything below 5x (5 times upper limit
examination is of paramount importance. of normal) is considered as mildly
elevated. Persistant elevation has higher
With the ease of doing liver function test significance.
(LFT) due to availabilty of automated
machines, more and more such tests are Causes
being asked for. In many such instances Asymptomatic elevation of liver
the result is mildly elevated liver transaminase levels can be categorized
enzymes. Mildly elevated liver enzymes into common hepatic, less common
in a seemingly normal individual trouble hepatic, and extrahepatic causes. (Table
even an experienced physician.An 1).
estimated 1% to 9% of people who have
no symptoms have high liver enzyme Common Hepatic Causes
levels when screened with standard NASH - It is one of the leading cause of
biochemistry panels.A US survey showed mildly elevated liver enzymes in
elevated alanine aminotransferase (ALT) asymptomatic individuals. Few of these
in 8.9% of surveyed people from 1999
to 2002, an increase from previous Table1: Causes of mildly raised
transaminases
reports.
Hepatic causes (Common)
Significance of Transaminases • Non Alcoholic Steato Hepatitis (NASH)
Both aspartate aminotransferase (AST) • Alcohol
and ALT are present in hepatocytes and • Viral hepatitis
are released into the blood in greater • Drugs and medication
amounts when hepatocytes are
Uncommon Hepatic causes
damaged. ALT is predominantly present
• Auto immune hepatitis
only in liver while AST is also seen in • Wilson's disease
Dr Vibhu V Mittal myocyte and erythrocytes.Because of • Hemochromatosis
Consultant Gastroenterologist
this elevations in ALT are more specific • Alpha-1 Antitrypsin deficiency
Department of Gastroenterology
for liver injury. Normally these are
Pushpanjali Crosslay Hospital Extra hepatic causes
present in serum at low levels, usually less
NCR-Delhi • Celaic sprue
than 30 to 40 U/L. Although the actual
values may differ from laboratory to • Hemolysis
laboratory, normal serum levels are • Muscular disorder
• Thyroid disorder
usually less than 40 U/L for AST and less
than 50 U/L for ALT. Ref: Krier M, Ahmed A. Clin Liv Dis 2009

patients may progress to cirrhosis and HCC. It is common in Uncommon Hepatic Causes
patients with diabetes mellitus, hypertriglyceridemia and Autoimmune hepatitis : Relatively uncommon. More
metabolic syndrome. Ultra sound, Computed tomography common in females. Is also associated with other auto
and Magnetic resonance imaging have good sensitivity immune phenomenon. Positive auto antibodies and raised
and specificity to diagnose fat in liver but they cannot immunoglobulin G levels with typical biopsy findings are
differentiate it from alcohol related fatty liver.
diagnostic of AIH
Alcohol: It is an important etiology of deranged liver
enzyme which can be easily diagnosed with an accurate Wilson's disease: It is an autosomal recessive genetic
history. Imaging or even liver biopsy cannot differentiate disease of copper metabolism. The frequency of this is 1:
alcoholic liver disease from NASH reliably. AST/ALT ratio 30000 in general population.Presence of Kayser Fleisher
>1 and raised gamma glutamyl transferase levels (KF) ring on ophthalmological examination is suuggestive.
suggest the possibility of alcohol related liver disease. Diagnosis can be established with low cerruloplasmin
levels and high 24 hr urinary copper levels.
Viral hepatitis: Hepatitis B and Hepatitis C are two
important treatable causes of liver disease. These cause Studies of Mild Aminotransferase Elevations
transient elevation of liver enzymes and testing is Only a few studies have documented the results of a
recommended even if repeat levels are normal. They can thorough evaluation of patients with mildly elevated
be diagnosed with HbsAg and Anti HCV tests respectively aminotransferase levels. These various studies which
included detailed evaluation including liver biopsies
Medications: Numerous medications have been showed, that in patients in whom apparent diagnosis could
associated with elevated transaminase levels, but the true
not be made after first and second line investigation;
incidence of liver injury from medications is unknown. Not
NASH is the most common etiology in these cases
only the standard drugs but other xenobiotics including
A large proportion of cases could not be diagnosed even
herbal products are also an important cause and detailed
after liver biopsy
history evaluating the same is important. Eliciting all
Compensated cirrhosis is diagnosed in significant
over-the-counter and prescription medications and
proportion of patients
stopping any potentially contributing agents may identify
the etiology.
But these studies were from an era prior to introduction of
Table 2: Hepatotoxicity of selected drugs serological testing of hepatitis C, moreover diagnosis of
NASH had inconsistencies in between various studies.
· Acetaminophen - acute hepatitis
· Allopurinol - granuloma
Approach to Patient
· Azathioprine - veno-occlusive disease, nodular
regenerative hyperplasia
As is clear with previous discussion, the data dealing with
· Diclofenac and other nonsteroidal anti-inflammatory the issue is scarce and most is retrospective in nature. There
drugs is also limited evidence on the most efficient evaluation of
· Hydralazine -granuloma asymptomatic patients with mildly elevated liver
· Isoniazid transaminase levels, so present consensus is to adopt a
· Methotrexate - fibrosis stepwise approach based on the prevalence of each
· Methyldopa
potential etiology.
· Nitrofurantoin - autoimmune-like disease
· Quinidine - granuloma
· Statins Step 1 – History and Physical examination
· Amiodarone - phospholipidosis Detailed history with emphasis on personal history of
· Corticosteroids alcohol consumption and drug history is paramount for
· Tetracycline evaluation. Presence of chronic liver disease merit
· Valproic acid
expedited work up for cause and confirmation of cirrhosis.
Ref: Navaro VJ et al. NEJM 2006
History and examination looking for obesity and

metabolic syndrome may suggest possibility of NASH. dilated abdominal veins,ascites or testicular atrophy)
History of previous surgeries, blood transfusion, IV drug should be done.
abuse etc. may suggest possibilty of viral hepatitis. History Even if there is no significant history or examination
of other auto immune phenomenon in a lady may point findings, testing for Hepatitis B (HbsAg) and Hepatitis C
towards auto immune hepatitis and a family history of liver (Anti HCV) is recommended.
disease especially pointing towards a autosomal recessive
inheritance pattern may suggest wilson's disease. Detailed With all negative evaluation on history and physical
physical examination especially looking for evidence of examination and negative viral markers, patient should
chronic liver disease (parotid swelling, loss of axillary hair, be kept in follow up with repeat measurement of ALT and
gynaecomastia, palmar erythema, dupytren's contracture, AST after a duration of 3-4 weeks. This is because in
Elevated ALT and AST
History and physical Examination

Discontinue hepatotoxic medication use, alcohol; repeat testing in 2-4 weeks
Persistent or unexplained ALT and AST abnormalities
HBsAg, Anti HCV

Fasting lipid profile, Blood sugar
USG abdomen
PT, albumin, complete blood count with platelet
Chronic liver disease Negative or consistent Abnormal

Or decompensation with non-alcoholic
Fatty liver disease
Further testing Workup
Lifestyle modification
Rx dyslipidemia DM
6 months
Resolve Persistent
Or
Improving
consider less common and extra hepatic cause
Observe
Positive or persistent >6months
Further testing – liver biopsy

many instances there may be a transient elevation of liver Step 3 – Uncommon causes and liver biopsy
enzymes due to a variety of identified or unidentified Six months of life style changes with treatment of any
factors such as inadverent drug ingestion or bystander identified cause is advocated. But if enzymes are
hepatitis due to systemic illness etc. This is based on clinical persistantly raised and worsening evaluation at an early
evidence from a recent trial by Lazo M et al from a date may be undertaken. The evaluation would be to rule
European centre in which it was shown that more than 30% out Auto immune hepatitis, Wilson's disease (if age <40
of adults had normal enzyme levels on retesting after a yr) and hemochromatosis. Extra hepatic causes could be
median of 17.5 d. considered if clinical condition points towards it.Celiac
disease is an important treatable condition in this respect.
Step 2 – Rule out common causes Similarly thyroid disorders can have deranged liver
With negative initial evaluation and persistantly elevated enzymes with persistant derangement and negative
enzymes on repeat LFT, further evaluation is warranted. A evaluation; liver biopsy may be indicated at 6 months.
study conducted by National health and nutrition survey
had shown that Hepatitis B, Hepatitis C and
hemochromatosis were responsible for 31% of such cases. References
1. Morisco F, Pagliaro L, Caporaso N, et al. University
However in India hemochromatosis is a rare disease and
of Naples Federico II, Italy. Consensus
only case reports are reported, as well the genetic
recommendations for managing asymptomatic
mutation responsible for it is much less than western data.
persistent non-virus non-alcohol related elevation
Non alcoholic steato hepatitis is the most common cause of of aminotransferase levels: suggestions for
these enzyme elevation after common causes are diagnostic procedures and monitoring. Dig Liver Dis.
excluded. So next logical step is to order for USG 2008;40(7):585-598.
Abdomen to document for fatty liver and markers of fatty 2. Krier M, Ahmed A. The asymptomatic outpatient
liver like fasting blood glucosa and fasting lipid profile. with abnormal liver function tests. Clin Liver Dis.
If there is concern about the p nossibility of chronic liver 2009;13(2):167-177.
disease, tests to evaluate synthetic function of liver such as 3. American Gastroenterological Association medical
prothrombin time, S. Albumin with Albumin/Globulin ratio position statement: evaluation of liver chemistry
along with complete blood count including platelet count tests. Gastroenterology. 2002;123(4):1364-1366.
is recommended.
This Issue of
is Partly Sponsored by “Suprima”
A division of INTAS
Blood Component Therapy
Anupam Chhabra
Introduction active bleeding are imprecise measures

Blood and blood components are of tissue oxygenation. Adequate or
considered drugs because of their use in inadequate fluid resuscitation can
treating diseases. As with drugs, adverse significantly alter the measured
effects may occur, necessitating careful hemoglobin concentration. In addition, a
consideration of therapy. The transfusion number of factors must be considered
of blood cells is also transplantation, in besides the blood hemoglobin level such
that the cells must survive and function as oxygenation in the lungs, blood flow,
after transfusion in order to have a hemoglobin, oxygen affinity and tissue
therapeutic effect. The transfusion of red demands for oxygen. Consequently, the
blood cells (RBSs) is the best tolerated adequacy of oxygen delivery must be
form of transplantation, but it may cause assessed in individual patients.
rejection. The rejection of platelets shown
as refractoriness to the platelet Dosage: A dose of one unit of
transfusion is relatively common in compatible Red Blood Cells will increase
multiple transfused patients. Fresh Frozen the hemoglobin level in an average sized
Plasma can be used to replace all adult who is not bleeding or hemolysing
coagulation factors, so it especially by approximately 1 g/dL or Hct by 3%.
useful to treat multiple coagulation In neonates, a dose of 10-15 mL/kg
deficiencies occurring in patients with isgenerally given, packed red cells with
liver failure, DIC, vitamin K etc. a hematocrit of approximately 60% will
Cryoprecipitate contains factor VIII, increase the hemoglobin by about 3
fibrinogen, von Wille brand factor g/dL.
(vWF), and factor XIII, thus this product
can be used to correct deficiency of these Response: Unless the recipient is
coagulation factors. bleeding or hemolysing, and provided
the transfused red cells are compatible,
Each patient must be evaluated the post-transfusion hemoglobin can be
individually to determine the proper accurately predicted from the patient’s
transfusion therapy, taking care to avoid estimated blood volume, baseline red
inappropriate over- or under- cell volume and transfusion volume.
transfusion. Transfusion decisions should Transfused red cells have a half-life of
be based on clinical assessment andnot approximately 30 days in the absence
on laboratory values alone. of other processes that would result in
Dr Anupam Chhabra red cell loss or premature removal.
Incharge-Transfusion Medicine Red blood cells
Pushpanjali Crosslay Hopital The decision to transfuse red blood cells Indications: Red blood cells are
NCR-Delhi should be based on clinical assessment of indicated for patients with asymptomatic
the patient and their response to any deficiency of oxygen-carrying capacity
previous transfusion as well as the or tissue hypoxia due to an inadequate
hemoglobin level. The function of a RBC circulating red cell mass. They are also
transfusion is to extend oxygen delivery indicated for exchange transfusion (eg,
to tissues. Hemoglobin levels during for hemolytic disease of the newborn)
December 2012
and red cell exchange (eg, for acute chest syndrome in Table 2. Administration of Packed Red Blood Cells
sickle cell disease).
Recipient
1. Transfusion is rarely indicated when the hemoglobin
(Patient) A B O AB
level is above 10 g/dL and is almost always
indicated inpatients when the hemoglobin level is A 1st 2nd
below 6 g/dL; choice choice
2. The determination of transfusion in patients whose
B 1st 2nd Rh Rh
hemoglobin level is 6-10 g/dL should be based on choice choice Positive Negative
any ongoing indication of organ ischemia, the rate
and magnitude of any potential or actual bleeding, O 1st
choice
the patient’s intravascular volume status and risk of
complications due to inadequate oxygenation. AB 2nd 1st
3. Transfusion for patients on cardiopulmonary bypass choice choice
with hemoglobin level ≤6.0 g/dL is indicated. Rh 1st 2nd

Positive choice choice
4. Hemoglobin level ≤ 7.0 g/dL in patients >65 years
and patients with chronic cardiovascular or Rh 1st
respiratory diseases is indicated. Negative choice
5. For stable patients with hemoglobin level between 7
anesthesia
and 10 g/dL, the benefit of transfusion is unclear.
6. Transfusion is recommended for patients with acute • Aseptic necrosis of the hip or shoulder (unless
blood loss more than 1,500 mL or 30% of blood indicated for surgery)
volume. • Uncomplicated pregnancy
7. Evidence of rapid blood loss without immediate
control blood transfusion is indicated. Platelets
Platelets are also referred to as whole blood derived
Table 1. In Neonates and Critically Ill Children platelets, random donor platelets (RDP), random platelet
Maintain HCT between Clinical Status concentrates. Platelet pheresis is also referred to as single
donor platelets, or SDPs.
40-45% Severe cardiopulmonary
disease (e.g., mechanical RDP are derived from Whole Blood and should contain ≥
ventilation >0.35 FiO2) 5.5 x 10^10 platelets per bag in approximately 50-90
mL of plasma. SDP is obtained using automated cell
30-35% Moderate cardiopulmonary
disease (e.g. less intensive separators and should contain ≥3.0 x 10^11 plateletsper
assisted ventilation such as nasal
CPAP or supplemental oxygen) bag in >200 mL of plasma.
30-35% Major surgery Dosage:

20-30% Stable anemia, especially if To help prevent or treat bleeding, transfuse as needed to
unexplained breathing maintain target platelet count.
disorder or unexplained poor Prophylactic platelet transfusion in surgical patients:
growth
i. Rarely indicated when the platelet count is >100 x
Controversial indications include Leg ulcers, Pregnancy, 109 /l
“Silent” cerebral infarct and/or neurocognitive damage. ii. Usually indicated when the count is <50 x 109 /l
iii. With intermediate platelet counts (50-100 x 109 /l) -
Inappropriate Indications and Contraindications: based on the risk of bleeding
• Chronic, steady-state (asymptomatic anemia) Surgical and obstetric patients with micro vascular
• Uncomplicated pain episodes bleeding:
• Infection I. Usually require transfusion if the platelet count is
• Minor surgery that does not require general <50 x 109 /l
December 2012
Table 3: Current Prophylactic Platelet Transfusion Triggers Patients at risk for transfusion-associated graft-versus host
disease (TA-GVHD) should receive gamma irradiated
Patient Category Platelet Count
platelets. The dose of platelets is determined by the pre-
All Patient 10,000/µl transfusion platelet count, blood volume and the presence
or
of additional risk factors. A dose of one random donor unit
Stable patient 5000/µl
per 10 kg body weight may be used as a guide.
Patient with fever or recent 10,000/µl
hemorrhage (now stopped) Response: Post-transfusion platelet counts should be
Patient with Coagulopathy, 10,000/µl obtained between 10-60 minutes after infusion to asses
on heparin, or with anatomic transfusion recovery. Generally, expect an adult platelet
lesion likely to bleed count increment of approximately 7-10,000/mm3 for
ii. Rarely require therapy if it is >100 x 109 /l each RDP given, or 30-60,000/ mm3 for each SDP given.
iii. With intermediate platelet counts (50-100 x 109 /l)- In neonates and infants, a dose of 5-10 mL/kg of platelets
based on the patient's risk for more significant (RDP or SDP) should result in a 50-100,000/mm3
bleeding increment.
iv. Vaginal deliveries or operative procedures
ordinarily associated with insignificant blood loss Transfusion Refractoriness:
may be undertaken in patients with platelet counts a) To assess the platelet survival a postinfusioncounts at
24 hours should be performed (in non-immune factors
less than 50 x 109 /l
such as sepsis, splenomegaly, DIC, etc.)
v. Platelet transfusion may be indicated despite an
b) Alloimmune refractoriness may develop when at least
apparently adequate platelet count if there is
two consecutive poor platelet increments at 10-60
known platelet dysfunction and micro vascular
minutes after transfusion.
bleeding.
vi. When the platelet count cannot be done in a timely
Contraindications:
fashion in the presence of coagulopathy, platelets
1. Thrombotic thrombocytopenic purpura (TTP),
may be given when thrombocytopenia is suspected.
Idiopathic thrombocytopenic purpura (ITP), Heparin-
induced thrombocytopenia, unless life–threatening
Transfusion of Platelets
hemorrhage exists.
SDPs and RDPs should be ABO-identical with the recipient
2. There is no role for prophylactic platelet transfusion in
when possible.
routine primary open heart surgery unless there is:
Table 4. Administration of Platelets
Recipient's (Patient's) Donor (Blood Unit)
ABO STATUS 1ST CHOICE 2ND CHOICE 3RD CHOICE 4TH CHOICE
AB AB A* B* O*
A A AB B* O*
B B AB A* O*
O O A B AB
Recipient's Donor (Blood Unit)
Rh D Status Rh positive Rh negative Rh positive Rh negative
Rh positive 1st Choice 2nd Choice 1st Choice 2nd Choice
Rh negative 2nd Choice 1st Choice 2nd Choice 1st Choice
*In non-availability of group specific platelet concentrate, non-group specific platelet concentrate can be transfused after consultation.
December 2012
i. Micro vascular bleeding and platelet count 4. Bleeding or prophylaxis of bleeding for a known
50,000/µl single coagulation factor deficiency for which no
ii. Microvascular bleeding (eg, post-operative chest concentrate is available.
tube drainage greater than 500 ml within 6 5. Thrombotic thrombocytopenic purpura.
hours) and non-diagnostic coagulation 6. Rare specific plasma protein deficiencies, such as C1-
abnormality. inhibitor.
3. Surgery or invasive procedure where platelet counts
is more than 50,000/µl, prophylactic platelet Contraindications:
transfusion is not indicated. 1. Increasing blood volume or albumin concentration
2. Coagulopathy that can be corrected with
Fresh frozen plasma
administration of Vitamin K.
Plasma consists of the non-cellular portion of blood that is
3. Normalizing abnormal coagulation screen results, in
separated and frozen after donation. It may be
the absence of bleeding.
prepared from whole blood or collected by apheresis.It
4. Hypovolaemia, plasma exchange procedures or
contains all coagulation factors.
treatment of immunodeficiency states.
Dosage: The amount of FFP needed depends on the
Cryoprecipitate
patient’s clotting factor levels, the levels needed to attain
Cryoprecipitate AHF is prepared by thawing FFP and and
a therapeutic result, whether or not the patient is bleeding,
recovering the precipitate. It contains factor VIII,
and the patient’s blood volume. If possible, coagulation
tests (ie, PT or INR and aPTT) should be performed before fibrinogen, vonWillebrand factor (vWF), and factor XIII.
the administration of FFP in a bleeding patient.
Dosage:
Indications: The number of cryoprecipitate units can be estimated
Fresh Frozen Plasma is indicated for use in patients with byusing the following calculation
the following conditions: 1. Weight (Kg) x 70mL/Kg = blood volume (mL)
1. Active bleeding due to deficiency of multiple 2. Blood volume (mL) x (1.0-hematocrit) = plasma
coagulation factors, or risk of bleeding due to volume(mL)
deficiency of multiple coagulation factors. 3. Fibrinogen required (mg) = (desired fibrinogen level
2. Severe bleeding due to warfarin therapy, or urgent (mg/dL) - initial fibrinogen level (mg/dL)) multiplied
reversal of warfarin effect by (plasma volume (mL) / 100).
3. Massive transfusion with coagulopathy and bleeding. 4. Bags of cryoprecpitate required = mg fibrinogen
required/ 250 mg fibrinogen per bag of cryo.
Table 5: Administration of Fresh Frozen Plasma
The frequency of dosing depends on the half-life and
Recipient Donor (Blood Unit) recovery of the coagulation factor that is being replaced
(Patient) A B O AB
(check factor levels).
st nd As a thumb rule - one cryoprecipitate unit per 7 - 10 kg of
A 1 2
choice choice body weight can be transfused.
Indications: Patients with fibrinogen deficiency where
B 1st 2nd there is clinical bleeding, an invasive procedure, trauma
choice choice
or disseminated intravascular coagulation .
O 2nd 3rd 1st 4th
choice choice choice choice
Administration of Cryoprecipitate
AB 1st Cryoprecipitate may not be ABO identical however ABO
choice
compatible cryoprecipitate is preferred. The
Note: Rh(D) positive plasma should not be given to Rh(D) compatibility testing is not necessary, Rh type need not be
negative women in the reproductive age group.
considered when using this component.
December 2012
Response: Pretransfusion and post-transfusion
coagulation factor levels should be determined to assess References
the adequacy of the cryoprecipitate dose. 1. Standards for Blood Banks/Bank Centers and
Transfusion Services, NABH.
Contraindications: This component is not generally 2. Transfusion Medicine Technical Manual Second
considered appropriate in the treatment of edition; Directorate General of Health Services,
i. hemophilia Ministry of health & Family Welfare, Govt. of India,
ii. von Will brand’s disease, or deficiencies of factor XIII New Delhi.
or fibronectin, unless alternative therapies are 3. Practice Guidelines for Blood Transfusion, second
unavailable. edition, American Red Cross.
4. Practice Guidelines for Perioperative Blood
Conclusions: Patients who require blood or blood
Transfusion and Adjuvant Therapies; ©2006
products, whether in life-threatening acute situations or as
American Society of Anesthesiologists, Inc.
a supportive therapy in chronic hematological disorders, Lippincott Williams & Wilkins, Inc.
must receive the required component only. Transfusion of
packed red blood cells should be used for situations in
which clear physiological indicators for transfusion are
present. Depending upon the condition and disease of the
patient prophylactic platelet transfusion trigger can be as
low as 10,000/µl. Before administration of FFP in a
bleeding patient coagulation profile should be obtained.
Fibrinogen concentration should be obtained before the
administration of cryoprecipitate in a bleeding patient.
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December 2012
An Approach to Headache
Dr Priya Gupta
Introduction A headache can be the result of a direct
Headache is one of the most common irritation of, or traction on, pain-sensitive
symptoms in neurology and one of the intracranial or extracranial structures.
most common reasons patients seek Inflammatory conditions such as
medical attention. Headache occurs due meningitis produce pain by direct
to activation of pain-sensitive structures irritation of these structures. Mass lesions
in or around the brain, skull, face, sinuses, including tumors and abscesses cause
or teeth. Headaches may occur as a pain by producing traction on these
primary disorder or be secondary to structures, most commonly on dural
another disorder. The most important vessels or the arteries of the circle of
task in evaluation of headache is to Willis. Factors that increase the pressure
determine whether a patient has a produced by such lesions will increase
primary or secondary headache, or a the intensity of pain. Headache
potentially life-threatening cause of produced by this mechanism is worsened
headache.
by the increase in central venous
pressure caused by the Valsalva
Pathophysiology of Headache maneuver. The patient will often note a
Headache consists of pain or discomfort more severe headache on awakening,
arising from pain-sensitive structures in which lessens somewhat after an upright
the head. These include extracranial position has been maintained for a
structures such as the skin, muscles, and period of time, due to a slight increase in
blood vessels in the head and neck;
brain edema induced by periods of
mucosa of the sinuses and dental
recumbency.
structures; and intracranial structures
including the regions of the large arteries Headache Classification
near the circle of Willis, the great Currently, the most widely used system
intracranial venous sinuses, parts of the for classifying headache is that of
dura and dural arteries, and cranial International Headache Society, the
nerves. The cranium, brain parenchyma, International Classification of Headache
ependymal lining of the ventricles, and Disorders, Second Edition. The ICHD-2 is
choroid plexus are all pain insensitive. designed mainly for diagnostic
Table 1. Pain Sensitivities of Structures in the head
Sensitive Insensitive
Extracranial Skin, muscles, fascia Skull (except periosteum)

Dr Priya Gupta Blood vessels
Mucosa of sinuses
Consultant Neurologist
Dental structures
Department of Neurology
Pushpanjali Crosslay Hopital Intracranial Large arteries near circle of Willis Parenchyma of brain
NCR-Delhi
Large venous sinuses Pia mater, arachnoid mater,
parts of duramater
Dural arteries and parts of dura Ependyma, choroid plexus

consistency for research purposes, but it is helpful in Table 3. Characteristics of Primary and Secondary
establishing the correct diagnosis which then guides headache
treatment. Part 1 of the ICHD-2 classifies primary Characters of Primary Headache
headache (ie, those with no other known cause) as 1 of 4 1. Recurrent attacks
main types. Secondary headaches are classified based 2. Symptoms free between the attacks
on aetiology, not on symptom profile. There are nine 3. Pain shift inside and location
categories of secondary headache (against eight in the 4. Clinical syndromes fulfill IHS* criteria
ICHD-1). 5. Physical examination normal
6. No organic causes
Table 2. The International Classification of Headache 7. Exception: drug-abuse headache
Disorders, 2nd edition
Characters of Secondary Headache
1. Progressive course
Part I: The Primary Headaches 2. Symptoms persist
1. Migraine 3. Pain select to anatomical lesions
2. Tension-type headache 4. Side-locked
3. Cluster headache and other trigeminal autonomic 5. Physical examination usually abnormal
cephalalgias
4. Other primary headaches
Table 4. Some Characteristics of Primary Headache
Part II: The Secondary Headaches disorders
1. Headache attributed to head and/or neck trauma
2. Headache attributed to cranial or cervical vascular Migraine Frequently unilateral and pulsating, lasting
disorder headache 4–72 h; occasionally with aura, nausea,
3. Headache attributed to non-vascular intracranial photophobia, or osmophobia
disorder Worse with activity, preference to lie in the
4. Headache attributed to a substance or its withdrawal dark, resolution with sleep
5. Headache attributed to infection
6. Headache attributed to disorder of homoeostasis Cluster Unilateral orbitotemporal attacks
7. Headache or facial pain attributed to disorder of headache at the same time of day
cranium, neck, eyes, ears, nose, sinuses, teeth, mouth or Deep, severe, lasting 30–180 min; often
other facial or cranial structures with lacrimation, facial flushing, or Horner's
8. Headache attributed to psychiatric disorder syndrome; restlessness
Part III: Cranial Neuralgias Central and Primary Facial Tension-type Frequent or continuous, mild, bilateral, and
Pain and Other Headaches headache viselike occipital or frontal pain that
1. Cranial neuralgias and central causes of facial pain spreads to entire head
2. Other headache, cranial neuralgia, central or primary Worse at end of day
facial pain
If a patient experiences a new kind of headache for the Evaluation of Headache

first time in close temporal relation to another disorder Evaluation focuses on determining whether a secondary
cause is present. If no cause is identified, it focuses on
known to cause headache and the headache is attributed
diagnosing primary headache disorders. The vast
to that disorder, the headache should be coded as a majority of headaches result from benign conditions, but
secondary headache. The headache is generally because the symptom can represent an early
considered to be secondary headache if it has at least manifestation of a potentially serious disorder, it
one of the following characteristics specified. necessitates thorough evaluation.
• The secondary disorder known to be able to cause · History
headache has been demonstrated. · Physical examination
• Headache occurs in close temporal relation to the o General physical examination
secondary disorder and/or there is other evidence of o Neurological examination
a causal relationship. · Investigations
• Headache is greatly reduced or disappears within 3
months (this may be shorter for some disorders) after History
successful treatment or spontaneous remission of the In most instances, a good clinical history is sufficient to
causative disorder. There are exceptions to this accurately diagnose a patient's headache and
general rule, for example chronic posttraumatic determines whether additional laboratory testing or
headache does not disappear 3 months after the neuroimaging is indicated on the basis of patient's
symptoms and signs.
trauma.
Table 5: History to be taken in a case of Headache headache history. The general physical examination
should include vital signs, funduscopic and cardiovascular
Temporal Profile: assessment, and palpation of the head and neck. A
· Acute vs Chronic (gradual, sudden, sub acute)
complete neurologic examination is essential, and the
· Time to maximal pain
findings must be documented.
· Frequency: For recurrent headaches, age at onset,
temporal pattern (including any relationship to phase of
menstrual cycle), and response to treatments (including Table 6: Physical examination
OTC treatments) are also noted.
Characteristics of Pain: Vital signs:
· Location and Radiation (diffuse, either unilateral or · Temperature, Blood pressure
bilateral, or localized) Headache and Neck examination:
· Duration (Intermittent, Constant ) · Scalp for swelling and tenderness
· Quality ( Throbbing, stabbing, dull, other) · Auscultation for bruits in H/N
· Quantity (Intensity of pain) · Temporal artery inspection and palpation
Prodromal Symptoms: · Temporomandibular joints palpation for tenderness
· Patients with migraine may report visual symptoms such as
and crepitance
scintillations, scotoma, or hemianopsia, malaise or psychic
disturbances, rarely hemiplegia or ophthalmoplegia may Eyes and Periorbital area examination:
also occur. · Note any lacrimation, flushing, and conjunctival injection
Alleviating and Exacerbating factors: · Intraocular pressure
· Valsalva acitivity: Causing onset of pain, think SAH; · Oropharynx examination for swellings
increases pain think any cause of increase ICP · Neck is flexed to detect discomfort, stiffness, or both,
· Coital: may precipitate rupture of aneurysm, benign indicating meningismus
orgasmic headache may also occur
· Cervical spine is examined for tenderness or restriction of
· Supine is worse: sinusitis, cerbral venous thrombosis,
movements
intracranial mass
· Supine is better: low pressure headaches
Neurological examination:
· Medications: nitrates and other vasodilators, · Mental status and level of consciousness
indomethacin, and oral contraceptives · Cranial nerve testing with particular attention should be
· Foods such as alcohol or those containing tyramine or given to detecting problems related to the optic,
sodium nitrates may precipitate vascular headaches oculomotor, trochlear and abducens nerves (pupillary
· Exercise, light, noise, etc reflexes, visual acuity, visual fields, fundoscopy, extra
· Head trauma occular movements)
Associated Symptoms: · Motor strength testing, deep tendon reflexes, sensation,
· Nausea/Vomiting, Photophobia, Phonophobia may be
pathologic reflexes
associated with Migraine
· Cerebellar function and Gait testing
· Autonomic symptoms such as lacrimation, nasal
congestion, facial flushing, or Horner's syndrome · Signs of meningeal irritation (Kernig's and Brudzinski's
accompany cluster headaches signs)
· Meningeal signs
· Neurological deficits
· Seizures
Red Flags
Medical History: Only a few headaches are secondary, but this category
· Constitutional symptoms, HTN, DM, hyperlipidemia, contains the most life-threatening diagnoses. Although
Smoking, Trauma prospective studies are lacking, several publications have
· Previous history of malignancy or systemic disease commented on historical and physical findings that are
· Family history should be investigated because migraine is considered red flags for serious problems based on
commonly familial clinical experience. Currently, these findings offer the best
means of identifying a secondary headache disorder.
Physical Examination Focal neurologic findings should prompt additional
The primary purpose of the physical examination is to evaluation. Among others, these findings include
identify causes of secondary headaches. The examination unilateral loss of sensation, unilateral weakness, unilateral
should target areas identified as abnormal during the hyperreflexia and papilledema.

Table 7: Red flags: following findings are of Table 9: Indications of Neuroimaging CT (or MRI) in
particular concern a patient of headache
Red Flags
1. Thunderclap headache
· Neurologic symptoms or signs (eg, altered mental status,
2. Altered mental status
weakness, diplopia, papilledema, focal neurologic
deficits) 3. Meningismus
· Immunosuppression or cancer 4. Papilledema
· Meningismus 5. Signs of sepsis (eg, rash, shock)
· Onset of headache after age 50 6. Acute focal neurologic deficit
· Thunderclap headache (severe headache that peaks 7. Severe hypertension (eg, systolic > 220 mm Hg or
within a few seconds) diastolic > 120 mm Hg on consecutive readings)
· Symptoms of giant cell arteritis (eg, visual disturbances,
jaw claudication, fever, weight loss, temporal artery
tenderness, proximal myalgias) In addition, if meningitis, subarachnoid hemorrhage, or
· Systemic symptoms (eg, fever, weight loss) encephalitis is being considered, lumbar puncture and CSF
· Progressively worsening headache analysis should be done, if not contraindicated by imaging
· Red eye and halos around light results.
Tonometry should be done if findings suggest acute
Table 8: Matching Red Flag findings with a cause for Headache
Suggestive Findings Causes
Neurologic symptoms or signs (eg, altered Encephalitis, subdural hematoma, subarachnoid or

mental status, confusion, neurogenic intracerebral hemorrhage, tumor, other intracranial mass,
weakness, diplopia, papilledema, increased intracranial pressure
focal neurologic deficits)
Immunosuppression or cancer Brain infection, metastases
Meningismus Meningitis, subarachnoid hemorrhage, subdural empyema
Onset of headache after age 50 Increased risk of serious cause (eg, tumor, giant cell arteritis)
Thunderclap headache (severe headache Subarachnoid hemorrhage

that peaks within a few seconds)
Combination of fever, weight loss, visual Giant cell arteritis

disturbances, jaw claudication, temporal
artery tenderness, and proximal myalgias
Systemic symptoms (eg, fever, weight loss) Sepsis, thyrotoxicosis, cancer
Progressively worsening headache Secondary headache
Red eye and halos around lights Acute angle-closure glaucoma
Investigations narrow-angle glaucoma (eg, visual halos, nausea, corneal

Most patients can be diagnosed without testing. However, edema, shallow anterior chamber).
some serious disorders may require urgent or immediate
Other testing should be done within hours or days,
testing. Some patients require tests as soon as possible.
depending on the acuity and seriousness of findings and
should be done in patients with any of the following
suspected causes.
findings:

Table 10: Neuroimaging, usually MRI, should be Table 11: Treatment of primary headache
done if patients have any of the following: Migraine Acute attacks
headache · Oral analgesics ± Antiemetic
· Focal neurologic deficit of subacute or uncertain
· Parenteral Analgesic ± Antiemetic
onset
(Contraindications: Peptic ulcer or lower
· Age > 50 years bowel disease, Diarrhoea )
· Weight loss · Triptans (Contraindications: Uncontrolled
· Cancer hypertension, Risk factors for CHD or CVD,
· HIV infection or AIDS Children under 12 years)
· Change in an established headache pattern · Ergotamine (Contraindications:
· Diplopia Ergotamine is not an option if triptans are
contraindicated and should not be taken
ESR should be done if patients have visual symptoms, jaw concomitantly with a triptan, Beta-blocker
or tongue claudication, temporal artery signs, or other therapy, not advised for children)
findings suggesting giant cell arteritis. Preventive therapy:
CT of the paranasal sinuses is done to rule out complicated · Betablockers- Beta-blockers (atenolol,
sinusitis if patients have a moderately severe systemic metoprolol, propranolol, bisoprolol) if
illness (eg, high fever, dehydration, prostration, not contra-indicated
tachycardia) and findings suggesting sinusitis (eg, frontal, · Antidepressants- amitriptyline (when
positional headache, epistaxis, purulent rhinorrhea). migraine co-exists with TTH, Another
Lumbar puncture and CSF analysis are done if headache chronic pain condition, Disturbed sleep,
is progressive and findings suggest idiopathic intracranial Depression)
hypertension (eg, transient obscuration of vision, diplopia, · Anticonvulsants- sodium valproate,
pulsatile intracranial tinnitus) or chronic meningitis (eg, topiramate
lethargy, vomiting, focal neurologic deficits). · Calcium channel antagonists - verapamil
Cluster Acute attacks:

Treatment headache · Subcutaneous sumatriptan 6 mg
Most patients with a primary headache require
· High dose/high flow rate oxygen
medication; however, other management methods also
Preventive therapy: Ergotamines,
may be useful. Secondary headaches usually resolve
corticosteroids, verapamil
when the underlying neurologic or systemic problem is
treated. Tension-type Episodic form: NSAID drugs
Primary headache headache Chronic therapy: Tricyclic antidepressants
· Acute treatment
· Preventive treatment
References
- Medical treatment 1. American Academy of Neurology. Guideline summary for
- Non-medical treatment clinicians: Migraine headache.
Secondary headache 2. Headache Classification Subcommittee of the International
· Symptomatic treatment Headache Society. The international classification of headache
· Specific treatment for causes disorders. 2nd ed. Cephalalgia. 2004, 24: (Suppl 1): 1-160.
3. Silberstein SD. Practice parameter: Evidence-based guidelines
for migraine headache (an evidence-based review): Report of
Key Point the Quality Standards Subcommittee of the American Academy
· Recurrent headaches that starts at a young age in of Neurology. Neurology. 2000, 55: 754-762.
patients with a normal examination are usually 4. Friedman AF. Headache. In: Baker AB, Baker LH, eds. Clinical
benign. neurology. New York: Harper and Row, 1979;2:Chap 13.
· Immediate neuroimaging is recommended for patients 5. Diamond S, Dalessio DJ. The practicing physician's approach to
with altered mental status, seizures, papilledema, headache, 3d ed. Baltimore: Williams and Wilkins, 1982.
focal neurologic deficits, or thunderclap headache. 6. Messlinger, K., and R. Burstein. (2000). Anatomy of central
nervous system pathways related to head pain. In The
· CSF analysis is required for patients with meningismus
Headaches, 2nd ed., (J. Olesen, P. Tfelt-Hansen, and K.M.A.
a n d u s u a l l y, a f t e r n e u r o i m a g i n g , f o r Welch, eds.), pp. 77 - 86. Lippincott Williams and Wilkins,
immunosuppressed patients. Philadelphia
· Patients with thunderclap headache require CSF 7. Kaniecki R. Headache assessment and management. JAMA
analysis, even if CT and examination findings are 2003; 289: 1430-33.
normal. 8. Steiner TJ, Fontebasso M. Headache. BMJ 2002; 325: 881-86.

Cerebral Venous Thrombosis: Not So Uncommon?
Dr Kapil Kumar Singhal

A 22 year old male presented to the of seizures. The possibilities which
hospital with complaints of headache for should be considered include
3-4 days. Headache was holocranial, 1. Intracranial space occupying lesion
moderate to severe intensity, not 2. I n f l a m m a t o r y g ra n u l o m a s -
associated with nausea, vomiting, Neurocysticercosis, Tuberculomas
blurring of vision and was not having any 3. Focal encephalitis
specific aggravating or relieving factors. 4. Vascular etiologies: ischemic lesion,
After 3 days of headache, he had focal parenchymal hemorrhages
abnormal sensation in the form of ant like 5. Vascular malfor mations with
crawling sensation in his right hand which hemorrhages
subsided after few minutes. These 6. Cerebral venous thrombosis
symptoms recurred a few times and on Neuroimaging was done on priority due
the day of presentation to the hospital, to presence of papilledema. (Fig 1-4)
he had a seizure. It started with
abnormal sensation, followed by MRI Brain revealed:
abnormal movement of hand and face 1. Diffusion weighted image shows tiny
and later generalization of seizure. He focal area of restricted diffusion in
did not have any previous history of right posterior frontal lobe,
seizures. He did not have any post ictal representing acute infarct.
weakness. He was a smoker, but non 2. Axial gradient FFE image shows
hypertensive and sugar levels were focal area of blooming in right
never tested previously. No significant posterior frontal lobe, c o n s i s t e n t
medical illness was present in the family. with hemorrhage.
3. Axial post contrast image shows
Clinical examination revealed a normal filling defect in posterior aspect of
systemic examination. Neurological
examination was unremarkable except
for early papilledema.
The patient was managed initially with

anti epileptic drugs and in view of
sensory phenomenon, a possibility of
focal seizure with right parietal
localization was considered.
Fig 1: Fig 2:
Dr Kapil Kumar Singhal
Consultant Neurologist A. Differential Diagnosis
Department of Neurology The presentation can be summarized as
Pushpanjali Crosslay Hospital focal seizure, possible right parietal
NCR-Delhi localization and signs of raised intra
cranial pressure. This gentleman
does not have any risk factors, no
history of fever and no past history Fig 3: Axial post Fig 4: MR Venography
contrast view

superior sagittal sinus, consistent with venous International Study on Cerebral Vein Thrombosis (ISCVT)
thrombosis. reported that headache (89%), paresis (37%),
5. MR venography showing diffuse partial filing defect in generalized (30%) or focal (20%) seizures, papilledema
superior sagittal sinus, confirming venous thrombosis. (28%), and mental status disorders (22%) were the most
frequent presenting symptoms and signs associated with
B. How to further evaluate for the cause? the diagnosis of CVT.
This patient presented with signs of raised intracranial
pressure and focal seizures. His MRI Brain revealed a small Etiology:
hemorrhagic infarct in right parietal area which CVT is usually multifactorial. Multiple etiologies may be
corroborated with his seizure semiology. MR Venography present in the same patient and evaluation must be done
showed non visualization of superior sagittal sinus. This for associated conditions depending on the clinical
confirms diagnosis of Cerebral Venous Thrombosis (CVT). scenario. Pregnancy and puerperal state are commonly
The does not have any apparent risk factors for associated with CVT in women. Hyperhomocysteinaemia
developing CVT. However, he was evaluated for is an independent risk factor for CVT and has been found
coagulation disorders, autoimmune disorders and in around 30% of patients, whether low folate levels also
hematological disorders. predispose to CVT is not known. Prothrombotic conditions
like congenital anomalies of coagulation pathway should
His serum homocysteine levels were very high be evaluated if no other apparent predisposing
(25.6meq/L), however, other parameters for conditions are present.
hypercoagulable work up (Coagulation profile, Protein C
and S levels, antithrombin III levels, lupus anticoagulant),
autoimmune markers (ANA, dsDNA, RA) and drug screen
were normal. There were no other clinical or laboratory
features to suggest any auto immune disorders or
underlying malignancy.
C. How can we manage this patient?

He was started on anticoagulants (low molecular weight
heparin), antiepileptics and measures to reduce intra
cranial pressure (Mannitol). Patient improved
symptomatically, his headache resolved and was
discharged on oral anticoagulants with advice to monitor
PT/INR levels regularly.
Discussion
Cerebral venous thrombosis (CVT) refers to occlusion of
both superficial and deep venous system of brain including Predisposing conditions
superior sagittal sinus, transverse sinus, straight sinus and Genetic prothrombotic states
deep veins of brain. CVT is a rare cause of stroke · Protein C, S or antithrombin deficits
accounting for around 5 cases per million of population, · Factor V Leiden,
though it is three times more common in women than in men. · Prothrombin 20210 GA
Presentation of CVT can be acute to chronic. The · methylenetetrahydrofolate – reductase (MTHFR)
presenting symptoms can vary from focal syndromes like mutations
focal seizures, focal weakness to encephalopathy. Patient Acquired prothrombotic states
can present with signs of raised intra cranial tension
· Antiphospholipid antibody syndrome
(papilledema, vomiting, transient visual obscurations),
· Vasculitis
multiple cranial nerve palsies or cavernous sinus syndrome
· Lupus, Behçet's disease, Wegener's granulomatosis
(proptosis, chemosis, fifth/third/sixth nerve palsies). The

Other inflammatory diseases Diagnosis:
· Inflammatory bowel disease, sarcoidosis Computerized Tomography (CT) scan of the brain is the
· Malignancy initial imaging modality in clinical practice. CT Brain is
· Any cancer, including CNS tumours usually normal in CVT or may show focal hemorrhage or
· Haematological nonmalignant diseases infarct. Occasionally signs of CVT like hyperdensity of
· Polycythaemia, thrombocytopenia, severe anaemia thrombosed sinuses may be seen. The gold standard for
· Thyroid disorders diagnosis of CVT is MRI to demonstrate thrombosed vessel
· Dural arteriovenous fistulae along with MR Venography to demonstrate non
· visualization of the thrombosed vessel. Parenchymal
Precipitating Factors abnormalities like infarct of hemorrhages can be
· Infections brain, meninges, ears, sinuses, etc.
visualized by diffusion weighted images (DWI) or
· Pregnancy, puerperium
gradient recoil echo(GRE) images. The imaging diagnosis
· Neurosurgery, recent head trauma, lumbar puncture,
of CVT is not easy and inter observer variation is
jugular catheter
significant.
· Surgery
· Dehydration
Prognosis:
· Illicit drugs
· Oral contraceptives
The acute fatality rate in CVT is around 4%, usually in
· Other drugs patients with signs of raised ICP. The overall functional
· L-asparaginase, other cytotoxic drugs, tamoxifen, outcome of CVT is much better than arterial stroke with
steroids, androgens, oestrogen replacement therapy most of the patients recovering without sequlae.
Clinical Suspicion of CVT
MRI T2*-weighted imaging + MRV No evidence of CVT

CT/CTV if MRI not readily available Consider other differential diagnosis
Arterial stroke
Idiopathic intracranial hypertension
CVT (Confirmed by imaging) Meningitis
Idiopathic intracranial hypotension
Brain abscess
Initiate anticoagulation (IV heparin or SC LMWH) Brain neoplasm
If no major contraindications among other
Neurological improvement Neurological deterioration

or stable or coma despite medical treatment
Continue oral anticoagulation Severe mass effect for No or mild mass effect on
For 3-12 months or lifelong ICH on repeated imaging repeated imaging
according of the underlying etiology
a. Transient reversible factor
b. Low-risk thrombophilia
c. High-risk / inherited thrombophilia May consider decompressive May consider endovascular
Severe mass effect for ICH on repeated imaging hemicraniectomy therapy (with or without
(lifesaving procedure) mechanical disruption)
All patients should receive support for the prevention of complication and symptomatic therapy
(eg, management of seizure, intracranial hypertension)

Treatment: • Treatment of the underlying condition, anticoagulants
The treatment of CVT includes management of and reducing intracranial pressure are the three
predisposing condition, anti thrombotics, lowering fundamental therapeutic interventions.
intracranial pressure and symptomatic treatment for
seizures, headaches and visual failure. A proposed References
algorithm for treatment of CVT is given below. 1. Saposnik G, Barinagarrementeria F, Brown RD Jr,
Anticoagulation with IV heparin (1000 U/ h, APPT Bushnell CD, Cucchiara B, Cushman M, et al;
1.5–2.5x control, for no more than 7 days) or SC low American Heart Association Stroke Council and
molecular weight heparin followed by warfarin with a the Council on Epidemiology and
Prevention.Diagnosis and management of
target INR between 2 and 3 is recommended for all
cerebral venous thrombosis: a statement for
patients with CVT, regardless of the clinical presentation
healthcare professionals from the American Heart
and imaging features. Warfarin should be maintained for
Association/American Stroke Association. Stroke.
6 months, or longer (eventually for life) in patients with
2011 Apr;42(4):1158-92.
genetic or acquired prothrombotic conditions.
2. Bousser MG, Ferro JM.Cerebral venous
thrombosis: an update. Lancet Neurol. 2007
Pearls: Feb;6(2):162-70.
• CVT can present with various neurological deficits and 3. Ferro JM, Canhao P. Cerebral venous and dural
a high index of suspicion with Neuroimaging is sinus thrombosis. Practical Neurology, 2003, 3,
essential for diagnosis. 214–219
• Evaluation of predisposing conditions like 4. Stam J. Thrombosis of the cerebral veins and
hypercoagulable states and hyperhomocystenimia sinuses. NEJM 2005; 352: 1791–98.
should be done.
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A Patient with Fever and Skin Lesion - A Case Report
Dr Ashok Grover and Dr Pankaj Nand Choudhary

Mrs SK 24 year old female with Procalcitonin – Normal, urine R/M –
complaint of high grade continuous fever Normal, MP antigen, dengue, typhoid &
for 6 day associated with chills and leptospira serology were negative, HIV
rigors. She developed giddiness, nausea was negative, urine and blood culture
vomiting headache followed by altered did not show any growth.
sensorium a day prior to admission.
CXR showed mild haziness at left lower
No history of seizure, burring of vision or
zone, USG abdomen showed hepato-
pain abdomen. splenomegaly, MRI brain was normal.
There was no significant past history.
CSF study showed protein 40mg%,
glucose 88mg%, cells 20 (L 90%),
On examination:
coagulam absent, India ink negative,
Pulse 116/min, BP 90/60 mmHg, pallor
Gm stain – no organism seen, PCR for
++, icterus +, Temp 990F, Chest – harsh
MTB negative, HSV I / II negative.
vesicular breath sounds, CVS - S1S2
normal, CNS-There was no focal Provisional diagnosis
neurological deficit but patient was Acute febrile illness with rash with
restless, not following verbal commands, altered sensorium
pupils b/l NS/NR, neck rigidity absent a D/D Viral encephalopathy
& planters were b/l withdrawal. Meningococcemia
Sepsis encephalopathy
Examination of skin revealed maculo-
papular rash over abdomen, back and Course during hospitalization
lower extremities. Patient was shifted to medical intensive
care unit, and put on Ceftriaxone 2gm
Investigation on admission: i/v BD, and other supportive treatment
on day 3 general condition of the
Hb 9.6 gm%
patient deteriorated, BP fell to 80mmhg
CRP 266 mg% systolic with HR of 140/min, SPo2 was
S Albumin 2.78 mg% 90% on high flow 02, examination of
chest revealed B/L basal crepts. ABG
TLC 15.08/cumm showed type I respiratory failure. CXR
S. bilirubin(T) 4.93mg% showed B/L haziness suggestive of
AlP04 570 U/L ARDS/acute pulmonary edema. Patient
was intubated and put on ventilator
Polymorphs 81% support and was put noradrenaline
SGOT 90 IU/L infusion.
Dr Ashok Grover Blood urea 74.6 mg%
Echocardiography showed hyporkinesia
Sr. Consultant Physician & Platelet count 40000/cumm of LV with EF of 20%, Pro-BNP was
Chest Specialist 2391pg/ml. CECT thorax was done
SGPT 52 IU/L
Dr Pankaj Nand Choudhary which showed B/L symmetrical ground
Consultant Physician S.creatinine 0.86 mg%
glass opacities with consolidation
Department of Medicine K+ 2.90 meq/l involving B/L lung fields likely
Pushpanjali Crosslay Hospital suggestive of ARDS.
PT/INR Normal
NCR-Delhi Patient developed high grade fever
Na + 131 meq/l (1060F) on 5th Jan 12, culture send form

ET secretions were positive for enterobacter cloacae interleukin 1 (IL-1), IL-6, and tumor necrosis factor (TNF).
which was sensitive to tigicycline. Patient was put on broad LOS is one of the important structures that mediate
spectrum antibiotics (tigicycline, meropenam and meningococcal attachment to and invasion into epithelial
teicoplanin). Meanwhile patient developed echymotic cells.
rashes over both lower limbs and abdomen. Scraping was
taken and Gm stain revealed no organism. An immunoglobulin A1 protease cleaves lysosomal
membrane glycoprotein-1 (LAMP1), helping the organism
Patient continued to deteriorate, tracheostomy was done to survive intracellularly.
on 7th Jan. On 12th Jan patient desaturated, went into
peripheral circulatory failure and had a cardiac arrest Individuals with immunity against meningococcal
and died. infections have bactericidal antibodies against cell wall
antigens and capsular polysaccharide. A deficiency of
Discussion: circulating antimeningococcal antibodies is associated
Probable diagnosis of this case is Meningococcemia is with disease.
caused by Neisseria meningitidis, an encapsulated gram-
negative diplococcus. Acquisition of N meningitidis can Impairment of the protein C anticoagulation pathway
result in asymptomatic pharyngeal colonization or leads to the development of purpura fulminans in
invasive disease. There are at least 13 serogroups, with meningococcemia.
the most important being serogroups A, B, C, and W-135.
Meningococcemia is defined as dissemination of Endotoxin, cytokines, and free radicals damage the
meningococci into the bloodstream and is a medical vascular endothelium, producing platelet deposition and
emergency, making early recognition of the disease vasculitis.
essential.
Serogroups A, B, and C account for most cases worldwide.
Patients with acute meningococcal infection can present Serogroups A and C predominate in Asia and Africa, and
clinically with one of 3 syndromes: meningitis, meningitis serogroups B and C predominate in Europe, North
with meningococcemia, or meningococcemia without America, and South America.
obvious meningitis.
Up to 95% of patients with meningococcal disease have
Pathophysiology meningococcemia and/or meningitis. Up to 50% have
Humans are the only known reservoir of N meningitis and meningococcemia without meningitis. Fulminant
can transmit the organisms by aerosols or nasopharyngeal meningococcemia occurs in up to 20%. Nosocomial
secretions. Meningococcal infection is preceded by transmission to patient care personnel and laboratory
nasopharyngeal colonization. Attachment to the staff is rare.
nasopharyngeal epithelial cells is aided by meningococci-
expressed pili, such as the type IV pilus encoded, which Persons with meningococcal disease may present with a
binds to human cell surface protein CD4 6. Meningococci nonspecific prodrome of cough, headache, and sore
then enter the bloodstream and spread to specific sites, throat. This is followed by rapid onset of fever with chills,
such as the meninges or joints, or disseminate throughout arthralgias, and myalgias. The potential rapidity of
the body. Five percent of individuals become long-term progression cannot be stressed enough.
carriers, most of whom are asymptomatic.
Meningococci have 3 important virulence factors, as In fulminant meningococcemia, collapse occurs within a
follows: few hours, with rapid enlargement of petechiae and
purpuric lesions.
A polysaccharide capsule (which also determines the
serogroup) enables the organism to resist phagocytosis. Patients with meningococcal disease appear severely ill.
A lipo-oligosaccharide endotoxin (LOS) can be shed in Tachycardia and mild hypotension are present.
large amounts by a process called blebbing, causing Fever is moderate. High fever is present in fulminant
fever, shock, and other pathophysiology. This is meningococcemia.
considered the principal factor that produces the high
endotoxin levels in meningococcal sepsis. Meningococcal Cutaneous manifestations of meningococcemia are
LOS interacts with human cells, producing common and can be the presenting sign of disease.
proinflammatory cytokines and chemokines, including Petechiae are the most common sign, occurring in 50-60%

of patients with meningococcemia; however, urticarial Thrombocytopenia may be present.
and maculopapular lesions also may occur initially. In meningitis, the CSF can be turbid in appearance, with
Petechiae are most often located on the extremities and elevated pressures and proteins, and low glucose levels.
trunk but may progress to involve any part of the body. In very early infections, CSF examination results may be
Petechiae may appear in groups under areas of normal.
pressure. CSF Gram stain yields a sensitivity of approximately
50% in patients with meningococcal meningitis. It can
With progression of meningococcemia, pustules, bullae, have a higher yield than blood cultures.
and hemorrhagic lesions with central necrosis can Detection of meningococcal capsular polysaccharide in
develop. Stellate purpura with a central gunmetal-gray CSF may be used for rapid diagnosis. It is sensitive for A
hue is characteristic and should be considered highly and C polysaccharides.
suggestive of meningococcemia. Gram-negative diplococci may be observed in punch
biopsy and needle aspiration specimens of skin lesions
Large maplike purpuric and necrotic areas related to the or buffy coat preparations. Gram-negative diplococci
development of DIC are characteristic of fulminant may also be recovered from joint fluid. Findings on
meningococcemia.(Purpura Fulmanis)
Gram stains of skin lesions remain positive for up to 2
days after the start of antibiotics and form a rapid
Congestive heart failure, gallops, and pulmonary edema
means of diagnosis, including when meningitis is not
may be present. Other evidence of end-organ damage
present and when spinal fluid culture findings are
may also rapidly appear.
negative owing to the administration of antibiotics.
Patients with fulminant meningococcemia rapidly Chest radiography is useful to evaluate for pneumonia
deteriorate clinically, with hypotension and respiratory and acute respiratory distress syndrome.
failure. Echocardiography can be used to evaluate for
myocardial dysfunction and pericarditis.
Pericarditis can occur during the acute disease or in the
recovery period and is associated with serogroup C Treatment
disease. Antimicrobial therapy is directed toward treatment of
active infection or used prophylactically to protect those
Differential Diagnoses exposed to N meningitidis through close contact.
· Dengue Fever Drugs effective in treating active meningococcal infection
· Gonococcal Infections include penicillin G, chloramphenicol in patients who are
· Influenza allergic to penicillin, and some cephalosporins (ie,
· Mycoplasma Infections cefotaxime, ceftriaxone, cefuroxime) used to treat
· Rocky Mountain Spotted Fever pediatric patients.
· Streptococcus Group A Infections
· Streptococcus Group B Infections Individuals with at least 4 hours of close contact with an
· Thrombotic Thrombocytopenic Purpura index patient during the week before onset of illness are at
an increased risk of infection. Individuals at risk include
Laboratory Studies housemates, daycare contacts, cellmates, or individuals
Definitive diagnosis of meningococcal infection requires exposed to infected nasopharyngeal secretions (eg,
culture of meningococci from blood, spinal fluid, joint through kissing, mouth-to-mouth resuscitation, intubation,
fluid, or, occasionally, from skin lesions. suctioning).
Cultures produce transparent, nonpigmented colonies
that are oxidase positive and nonhemolytic. Rifampin and ciprofloxacin are commonly used for
The sensitivity of blood culture is 60%-80% in chemoprophylaxis. Rifampin may eradicate carriage in up
untreated patients. to 80-90% of individuals, but resistant strains have
Cerebrospinal fluid (CSF) culture yields a sensitivity of occurred. Other agents that can be used include
up to 70% in untreated patients. ceftriaxone and azithromycin. A single dose of
Polymorphonuclear leukocyte levels are usually intramuscular ceftriaxone may be used in children or
elevated, but they may be within the reference range adults. Vaccination should be adjunctive to antibiotic
or low. chemoprophylaxis in susceptible contacts in epidemics.

Communication for Doctors
Dr RCM Kaza
Communication is an essential skill for reasons and avoid failures, it is
any doctor. This aspect of a doctors’ work necessary to understand the process of
is often not given the attention it deserves communication. There are various
in medical education, and unfortunately aspects in this process which functions as
leads to many misunderstandings in a unitary whole. The individual who
Doctor-patient relationship. These skills starts the communication may be
are neither rare nor difficult to acquire. designated the sender. The sender
However, they need attention and encodes thoughts and ideas and sends
cultivation. them out to the receiver who has to
decode them to understand them. The
Broadly, communication may be defined intermediaries are the language of
as the process of mutual exchange of communication, and the medium, which
information and understanding by any the speaker wishes to use. All these are
effective means. Special attention needs interlinked and any break in the chain
to be paid to non-verbal communication results in failure of communication.
by way of emotional expression or body
There are many barriers to effective
language, whic h forms 90% of
communication. These are perception
comm unication. Therefore, it is
barrier, Inflection barrier, Inference
mandatory to attend to non verbal cues
barrier, Language barrier and so on.
to ensure an effective communication. Each of these barriers may have many
Often, the body and words speak in a underlying issues that impinge on
different language which serves to block effective communication. A detailed
the message that is intended to be understanding of these barriers is
delivered. essential for successful communication.
Counseling is yet another essential skill However, at the heart of communication
for the medical practitioner. There are between a Doctor and patient is the art
many difficult decisions that the patient of listening also called active listening.
may have to make about their health. It is Active listening is a skill by which a
the duty of the doctor to help them make Doctor not only listens to the patient but
those decisions. Patients trust their doctor also effectively conveys to the patient
explicitly and implicitly. Thus, a face-to- that they are listening. This may be done
verbally or by body language. This kind
face interaction between the Doctor and
of careful listening helps the doctor
patient is the best environment that helps
understand/decode the patient’s
the patient taking the final decision. In problems and concerns. During such
Dr RCM Kaza fact, counseling demonstrates in an interactions, patients convey disease
Director Professor Surgery admirable way, all the features of an detail and also their worries, concerns
Maulana Azad Medical College effective transaction such as active and attitudes. All these issues are
New Delhi listening, empathy, the art of open ended framed by the patient in their own
questions and clear explanations. language, with their own nuances in an
encoded fashion. The art of active
Despite best efforts, communication may listening requires attention and practice.
fail many a time and with disastrous This can be demonstrated and practiced
consequences. In order to understand the until it becomes a habit.
December 2012
Current HIV Scenario and India’s Concerted Action -
Plan to Tackle the Epidemic:
Ishwar S Gilada
In the run-up to the World AIDS Day, Death is generally not due to HIV
several success stories from many parts infection itself, but the opportunistic
of the country helps turning it into a Day infections (OIs) that occur when the
of Celebration PHO, the country's first immune system can no longer protect the
NGO in the crusade against AIDS since body against agents normally found in
1985, had established in 2004 that HIV the environment or the secondary
was leveling off in Mumbai, as it had cancers. The appearance of any one of
seen a downward trend among sex more than 25 different OIs, along with a
workers and flattened graphs among CD4 count less than 200 cells per c/mm
general population. Any change, upward of blood provides the clinical diagnosis
or downward, in rates of HIV or Sexually of AIDS in HIV-infected individuals. The
Transmitted Diseases happens in high- most common OI seen in HIV is TB in India
risk population, is subsequently followed and Pneumocystis carinii pneumonia
by a similar trend in general population (PCP) in the western countries. Bacterial
with a gap of 5-7 years. pneumonia and PCP, caused by the
fungus Pneumocystis jiroveci are also
The global AIDS Epidemic has completed commonly associated. In the late phase
30 years of its devastating presence. HIV Miliary TB, Extra-pulmonary TB and
care in India has completed 25 years. bacterial infection by Mycobacterium
The AIDS virus is perplexing as it moves avium can cause fever, weight loss,
slower than other infective organisms, anemia and constipation alternating
thus permitting years of symptom-free with diarrhea. Bacterial infections of the
infectivity. Despite ranking third in HIV GIT commonly cause diarrhea, weight
numbers, because of its affordable anti- loss, anorexia and fever. Most common
HIV drugs India globally prevents deaths diarrhea is caused by Cryptosporidia,
and ameliorates the suffering of millions Microspora and Isospora Belli
of HIV+ people. organisms, giving rise frequent watery
stools. During advanced stage, diseases
Initially HIV was found mainly in Sex caused by protozoal parasites,
Workers and professional blood donors especially toxoplasmosis and fungus
and their clients/buyers. Today, the especially cryptococcosis of the brain
disease has entered the third phase of are common. In addition people with
epidemic with housewives and children AIDS often develop other fungal
being infected with HIV. It has gone from infections. Thrush, an infection of the
Urban to Rural areas, crossed from high- mouth by the fungus Candida albicans, is
risk to low risk and from sex workers to most common from the early phase.
housewives. In India, there is a massive
single male- migration to industrialized The disease forecast of early 1990s has
cities/towns, and sex with multiple and c hanged to become a c hronic
often-unknown partners is an established manageable disorder now. People
behavior in males between 20-45 years infected with HIV can survive up to 30
Dr Ishwar S Gilada of age. There are persons traveling for years now – 10-15 years without ART
Secretary General Peoples Health their business and having good time just and another 15 years on ART. However,
for fun, including sex indiscreetly.
Organisation (India) - PHO this is possible if the patient is under
President, AIDS Society of India medical care and follows healthy
HIV infection is truly a preventable
Chairman, Unison Medicare & infection. Both the monetary and human lifestyle protocol, regular treatment and
Research Centre costs for prevention are far less when meticulous follow-ups. Alcohol,
compared to costs of treatment. The cost recreational drugs, smoking and
of HIV management in India is far less tobacco hastens disease progression
than in western countries. and hampers recovering process.
December 2012
Treatment for only richer countries and the rich in poorer What India needs to learn? We must critically evaluate
countries has become affordable to most countries. India is the state-run and NGO programs, replicate best practices
at crossroads vis-à-vis HIV that it makes imperative to look and shun the unsuccessful ones. We should provide three
back in the recent past, take stock of what has been tiered (not free for all) ART with quality care and should
achieved and what has been amiss in order to decide move from 'Donor-dependence' to 'Self-reliance'. We
future plan for a better tomorrow. The Saving grace for should focus to reduce vulnerability of women and children
larger Indian population from HIV is the Indian culture, the and make PPTCT a national emergency with 100%
responsiveness of its youth, efforts of voluntary NGOs and coverage. There should be a strong focus on Youth and de-
medical caregivers and yeomen contribution of our addiction as more than 50% new infections are among
pharma lobby. those below 30.
Treasure India’s Asset: India’s clinically oriented, We are facing an extremely challenging situation with
conservative, comprehensive and holistic care has earned Multi-drug resistant and extremely drug resistant
accolades. Its wait-n-watch approach in starting anti- (MDR/XDR) Tuberculosis and HIV, Immune Reconstitution
retroviral treatment (ART) is indeed blessing in disguise for Inflammatory Syndrome (IRIS) – a serious disease situation
HIV patients (as against ‘Hit-Early, Hit-Hard’ approach of caused by regaining the lost immunity following successful
the West). It improves quality of life, increases survival, ART, marriages/alliances among HIV +ve people, jobs for
reduces cost and spares them of impending drug- recovered people and medical Insurance for them. What is
resistance and adverse effects for years. Indian culture of not yet discovered is effective Vaccine for HIV prevention
joint families and lasting marriages with integrity in women among risk takers and vaginal Microbicide to prevent its
folks have been an asset in providing psycho-social transmission among women.
support and reduced transmission. The age at the first sex
is higher in India than the West or Africa. There is no other disease that has triggered such a fast and
quality research in short span of time. We know enough on
“One Tablet a Day: Keeps HIV at Bay!” treatment pathogenesis and epidemiology front. Knowledge on
invented in India made ART cheaper, safer and easier. The AIDS is fast evolving and that necessitates timely update
yearly cost of three-in-one cheapest first-line combo has of doctors providing HIV care. United Nations Secretary-
come down from US$ 11452/- per patient to $69. General Ban Ki-moon suggested strategy of the "three
zeros" - zero new HIV infections, zero discrimination and
What is amiss?: India records 18,000 children getting zero AIDS-related deaths. Let us pledge to work together
HIV from 65,000 HIV+ mothers annually, where as there to realize this vision for all of the world's people. India's
are strategies to prevent each of them. HIV+ women strategy of working on vulnerable groups at highest risk of
received only single-dose Nevirapine in an outdated contracting HIV is now paying off dividends and is
strategy meant for Africa. Sadly, less than 15% of the projected to avert 3 million infections. India’s success
pregnant women received Prevention of Parent to deserves praise, but there is no room for complacency.
Children Transmission (PPTCT); only 60% of sex workers
are reached with HIV prevention program and 40% of How HIV is transmitted?
them identify correct ways of prevention methods. Only HIV is spread through the exchange of bodily fluids,
30% of the infections are recorded at NACO, due to
primarily semen, vaginal secretions, blood, and blood
inherent flaws in the reporting system. Half of the infected
products. It cannot be transmitted through casual contact.
people do not know their HIV status. Our efforts to make
There are four main modes of transmission: Sexual,
the risk-takers understand their vulnerability have been
Parenteral, Perinatal and Accidental. The primary mode
inadequate nationally. Initially, most of the national
energy and funds were wastefully spent on 'surveillance' of infection in India is through sexual transmission, mainly
without 'interventions'; while only third of adults with heterosexual. The basics of each mode of transmission are
advanced HIV infection are receiving ART (up from 6% in outlined here:
2005); while 20% patients at NACO’s free roll out are
dead, 12.5% have lost to follow-up or stopped ART in 2 What is the Risk?
years. Thanks to the Supreme Court order of 16th Occupational Needle-prick
December 2010, there is universal access to even Second- Per- cutaneous 0.3%
line ART that includes patients treated by private Mucous membrane 0.09%
practitioners with initial regimen and with its previous Sexual transmission (single contact) 0.018% to 3%
order in 1998, India’s total blood supply is HIV screened Mother to child (in natural course) 25%
and is safe. Infected blood/ blood products 95%
December 2012
Rational Treatment of Osteoarthritis
Dr UK Sadhoo
Osteoarthritis is the commonest cause of such as Hyaluronic acid intraarticularly,
joint pains. Its precise cause is unknown. Glucosamine/Chondroitin and
As longevity increases, more and more acupuncture remains debatable.
Indians are succumbing to it. In our
country, knees are most involved though
Surgical options are:
any joint is susceptible. Besides age,
other factors such as lack of exercise, 1) Arthroscopy with limited benefits,
indifferent diet and sedentary lifestyle 2) Osteotomy in relatively early stages
are all contributory factors. in which redistribution of stresses is
Trauma, infection, inflammatory arthritis the aim and, if done for correct
also culminate in arthritis. indications, can yield good results
Treatment has two aspects: Surgical and for indefinite periods and finally,
non-surgical. 3) Joint replacement. The last option is
major surgery, costly, entails lot of
UK Sadhoo
Consultant Orthopedic Surgeon Non surgical treatment includes, physiotherapy later to achieve full
Pushpanjali Crosslay Hospital a n a l ge s i c s / a n t i - i n f l a m m a t o r i e s, benefits. Many patients who would
NCR-Delhi Physiotherapy, exercises and weight otherwise be crippled and bed-
reduction. These can yield substantial ridden are benefiting from
results. Efficacy of visco-supplements Replacement surgery.
with best Compliments from
OBPPL Orange Bio Science Products Pvt. Ltd.
IVD Products, Immuno Histo Chemistry Staining,

Microscopy Stains, Life Science and Analytical Syatems,
Service Contract for Multi brand Equipments
Contact:
Delhi Office: 101, Ashoka Apartment, Ranjit Nagar Commercial Complex, New Delhi -110008.
Tel: 011-25701441 | Mobile: 9811153763, 9811154339
Registered Office: 6, Bijoy Bose Road, off D L Khan Road, Bhawanipur, Kolkata – 700025
Tel: 033241-91876 | Web:www.orangebioscience.com
E-mail: dipak@orangebioscience.com, manchanda@orangebioscience.com
December 2012
Fever in the ICU
Amit Gupta
Introduction m e m b ra n e s b u t c o n s i d e r e d
Fever is a common problem in the ICU. It unreliable as it is influenced by
could be due to infectious and non- environmental temperatures, mouth
infectious causes. Our objective is to breathing etc. Examples – oral
review a rational approach to the t e m p e ra t u r e, a x i l l a r y, s k i n
management of fever in ICU patients. temperature
l Core temperature measurement - It
Definition is not influenced by external factors
Fever is a co-coordinated neuro and more accurately reflects
endocrine, autonomic and behavioral temperature in the internal organs.
response that is adaptive, and an Examples – pulmonary, rectal,
essential part of the acute-phase esophageal, urinary, tympanic
response to immune stimulus or tissue membrane.
injury. It is co-coordinated by the
hypothalamus with neural input from “Fever” in the ICU patients
peripheral thermoreceptors and humoral Normal temperature is 98.2O F (36.8O C)
cues from inflammation or infection. with diurnal variations of temperature
with evening rise up to 100O F (37.8O C).
Benefits of fever1, 2 Society of Critical Care Medicine
It enhances parameters of immune (SCCM) and Infectious diseases society
function, improves antibody production, of America recommend investigations in
activates T-cells, produces cytokines and the ICU if temperature is above 101O F
enhances neutrophil and macrophage (38.3O C).
function. A positive correlation has been
seen between maximum temperature on Approach to fever in the ICU5
the day of bacteremia and survival. l What are the causes of fever in ICU?
Temperature > 38 °C improved survival l How do I act when I see a
in patients with SBP. temperature spike?
l What investigations do I send?
The downside of fever l How do I treat the fever?
It increases cardiac output, oxygen
consumption, carbon dioxide production The obvious focus
and basal metabolic rate leading to l Community acquired pneumonia
poorer neurological outcomes in patients l Acute CNS infection
with stroke and traumatic brain injury l Urinary tract infection
who manifest with fever. Fever is poorly l Abdominal focus of infection
tolerated in patients with reduced l Wound infection / Pus collections
cardio-respiratory reserve. Maternal l Trauma with infection
Dr Amit Gupta fever has been a cause of fetal
Consultant and Head, malformations as well as spontaneous Why do these patients come to the ICU
Critical Care abortions3. l Ventilatory support – respiratory
Pushpanjali Crosslay Hospital failure, pneumonia
NCR-Delhi Measurement of temperature4 l Hemodynamic support – shock
It includes- l Renal replacement therapy – renal
l Pe r i p h e r a l t e m p e r a t u r e failure, severe acidosis
measurement- It is measured in the l Monitoring, Neurological
outer 1.6 mm of skin or mucus dysfunction, Hematologic
December 2012
Acute undifferentiated fever Non-infectious causes of fever in ICU
l Fever with thrombocytopenia
l Fever with hepato-renal dysfunction Brain Cerebral infarction/hemorrhage,
l Fever with pulmonary renal syndrome sub arachnoid hemorrhage
l Fever with altered sensorium Heart Acute myocardial infarction, pericarditis
Pulmonary Aspiration, atelectasis, pulmonary
Fever with thrombocytopenia embolism, ARDS
l Malaria (notably falciparum) Abdomen Ischemic bowel, gastrointestinal bleeding.
l Dengue pancreatitis, hepatitis. cirrhosis, adrenal
l Leptospirosis insufficiency
l Rickettsial infections Vascular Deep vein thrombosis, thrombophlebitis
l Viral fevers Cutaneous Decubitus ulcers
Miscellaneous Drug fever, reaction to radiological
Fever with hepato-renal dysfunction contrast, fat embolism, neoplasms, blood
l Malaria (falciparum) transfusions, transplant rejection. gout.
l Leptospirosis
l Scrub typhus l Decreasing urine output
l Fulminant hepatic failure l Increasing lactate levels
l Worsening conscious state
Fever with pulmonary-renal dysfunction6 l Falling platelet counts
l Malaria (falciparum) l Worsening coagulopathy
l Leptospirosis
l Scrub typhus
NO
l Hantavirus infection
l Small spike
l Severe legionella / pneumococcal pneumonia
l No hemodynamic instability
l Carefully examine clinically for an obvious focus of
Fever with altered sensorium
l Malaria – cerebral malaria infection
l Encephalitis
l Meningitis Investigations
l Typhoid fever l Blood – counts with peripheral smear, procalcitonin
l Septic encephalopathy l Imaging – CXR, Scans as indicated (abdomen, sinus, CT
l Brain abscess brain)
l Cultures as appropriate – ETA, BAL8, Urine, Blood
Infectious causes of fever whilst in ICU cultures (peripheral and through lines), cultures from
l Ventilator associated pneumonia7 pus, wound etc, Stool for clostridium
l Catheter related blood stream infections l Assess if lines are “old” and if there is any evidence of
l Urosepsis line sepsis - re-site line if indicated
l Intra-abdominal infections l Change urinary catheter
l Sinus infections l May need NG change – if sinus infection suspected
l Diarrhoea l Do not forget about
l Fungal infections including candidemia - Acute Lung injury/ARDS, Aspiration
l Surgical wound infections - Deep venous thrombosis, thrombophlebitis
l Acalculous cholecystitis - Drug fever
l Endocarditis - Decubitus ulceration
l Meningitis
Treatment
How do I act when I see a temperature spike?
l Antipyretics in patients with neurological disorders or
l Should I be worried?
poor cardio-respiratory reserve.
YES l Administer or change antibiotics in an unstable patient
l In an immunocompromised patient – choose to treat with broad spectrum antibiotics and
l Hemodynamic instability deescalate depending on cultures & clinical response.
December 2012

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Chronic Kidney Disease - Role of Physician in

The Management And Prevention

Vol. 11, Issue 4, October 2012

Evaluation for proteinuria

Not at ­ risk at ­ risk

Standard dipstick Albumin specific dipstick

>1+ Negative / trace Negative positive

Total protein / creatinine ratio Albumin / creatinine ratio

>200 mg/g <200mg/g <30 mg/g >30mg/g

Recheck at periodic health evaluation

Vol. 11, Issue 4, October 2012

Class of drug Safety profile in renal disease Remarks

1st generation sulphonylureas Unsafe Risk of prolonged hypoglycaemia

2nd generation sulphonylureas Glipizide safe Glipizide is preferred. Others to be avoided.

a-Glucosidase inhibitors Unsafe Possible hepatotoxicity

Biguanides Unsafe Risk of lactic acidosis

Thiazolidinediones Safe Volume retention may occur especially with insulin

Meglitinides Repaglinide safe Short half-life and minimal renal excretion of

Amylin analogs Safe No dose adjustment required for moderate to severe

Vol. 11, Issue 4, October 2012

Vol. 11, Issue 4, October 2012

CKD Stage GFR Range Phosphorus Calcium (corrected) Ca × P Intact PTH

30 – 59 2.7 – 4.6 8.4 – 10.2 35 – 70

15 – 29 2.7 – 4.6 8.4 – 10.2 70 – 110

<15, dialysis 3.5 – 5.5 8.4 – 9.5 <55 150 – 300

Introduction alternative etiology”.

Non-ionic - Iohexol Iodixanol 2. Diabetes Mellitus

3. Reduction of Effective Intravascular volume

Vol. 11, Issue 4, October 2012

­ PGE ­ Endothelin Systemic

¯Blood flow ¯O2 delivery O2 consumption

Direct cellular toxicity Renal medullary hypoxia

Contrast induced nephropathy (CIN)

ANP, atrial natriuretic peptide; PGE, prostaglandin; PGI, prostacyclin

findings have not consistently been shown to be specific for 1. Hydration

Vol. 11, Issue 4, October 2012

Vol. 11, Issue 4, October 2012

Moderate-to-High risk for CIN Emergent Procedure?

Fig 3: Algorithm for prevention of CIN IV Acetylcysteine?

Table 4: Dose of peri-procedural Intravenous fluids

Vol. 11, Issue 4, October 2012

Vol. 11, Issue 4, October 2012

Site of obstruction Etiology

Neoplastic- Wilm's tumor, renal cell carcinoma, Upper tract

Vol. 11, Issue 4, October 2012

Intravenous Functional and anatomical Retrograde Pyelography

Whitaker test Detect and differentiate degree

CT Scan and MRI An accurate method to detect Whitaker Test

Vol. 11, Issue 4, October 2012

Vol. 11, Issue 4, October 2012

In difficult cases where retrograde stenting is unsuccessful,

Vol. 11, Issue 4, October 2012

Dr Sanjiv Mahajan and Dr Sanjay Gupta

Introduction any of the following conditions mandates

1. Vascular access: It is the site on the body where blood is

Sustained Low-efficiency Dialysis (SLED)

Continuous Renal Replacement Therapy

Vol. 11, Issue 4, October 2012

Types of Peritoneal Dialysis

Vol. 11, Issue 4, October 2012

Not at risk at risk

PGE Endothelin Systemic