Nephrology

Internal and critical care medicine study notes

Dr Ali Ragab
Critical Care Medicine
Damanhur Medical National Institute
 Nephrology
Internal and critical care medicine study notes

Dr Ali Ragab

Critical care medicine

Damanhur medical national institute

Facebook at (ali_ragab_ali@yahoo.com)

Dr. Ali Ragab 2

Contents

Presentations of renal diseases 5

Urine 9
Urinalysis 12
Urinary tract infections 14
Acute kidney injury 22
Chronic kidney disease 38
Renal biopsy 47
Renal replacement therapy 48
Glomerulonephritis 55
Specific types of glomerulonephritis 57
Nephrotic syndrome 61
Histological patterns of nephrotic syndrome 65
Diuretics 69
Acute interstitial nephritis 74
Chronic tubulo-interstitial nephritis 75
Analgesic nephropathy 76
Urate nephropathy 77
Hypercalcemia 78
Radiation nephritis 78
Nephrotoxins 79
Rhabdomyolysis 81
Renal vascular disease 83
Hemolytic uremic syndrome 84
Thrombotic thrombocytopenic purpura 85
Diabetes mellitus and the kidney 86
Cholesterol emboli 88
Renal tubular disease 89
Renal tubular acidosis 89
Fanconi syndrome 91
Cystinosis 92
Hereditary hypokalemic tubulopathies 93
Inherited kidney disease 94
Autosomal dominant polycystic kidney disease 94
Autosomal recessive polycystic kidney disease 95
Medullary cystic disease 96
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Alport syndrome 97
Hyperoxaluria 97
Cystinuria 98

Dr. Ali Ragab 4

Presentations of renal diseases

Renal disease presents with rather few clinical syndromes listed below

Renal pain

Renal pain is usually a dull ache, constant and in the loin

It may be due to

Renal obstruction (look for swelling tenderness)

Pyelonephritis
Acute nephritic syndrome
Polycystic kidneys
Renal infarction

Renal (ureteric) colic

Characters

Ureteric colic is severe waxing and waning loin pain

Radiating to the groin or thigh
May be associated with fever and vomiting

It is caused by

Renal stone, clot, or sloughed papilla

Urine frequency with dysuria

Urine frequency with dysuria (pain on voiding) suggests a UTI

Dr. Ali Ragab 5

Oliguria

Oliguria is a urine output of <50mL/kg/hr

Pathological causes are

Pre-renal (decreased perfusion)

Intrinsic renal (renal parenchymal disease)
Post-renal (obstruction)

Polyuria

Polyuria is defined as a urine volume in excess of 3L/d

Usually from

High fluid intake

Diabetes mellitus
Diabetes insipidus
Hypercalcemia
Hypokalemia
Renal medullary disorder (impaired urine concentration ability)

Acute kidney injury (AKI)

Previously termed acute renal failure

Indicated significant decline in renal function occurring over hours to days

AKI usually occurs secondary to

Hypotension
Hypovolemia
Sepsis
Urinary obstruction
Primary renal disease is a less common cause

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Proteinuria and nephrotic syndrome

Normal protein excretion is <150mg/d

Nephrotic syndrome = proteinuria >3g/d, hypoalbuminemia, edema
Nephrotic range proteinuria (>3g/d) is almost always a sign of glomerular
disease

Hematuria

Blood in urine may arise from anywhere in the renal tract

Etiology

Take hematuria seriously, as it may be the only sign of GU malignancy

(especially if >40yrs old and smoker)
However in the majority of cases it has a benign cause (eg infection, renal
stone)

When to refer and to whom

Urology Nephrology
Visible hematuria All patients, any age <40yrs, cola-colored urine, recent
infection, eg URTI
Symptomatic non All patients, any age
visible hematuria
Asymptomatic non Persistent, >40yrs <40yrs with BP >140/90, eGFR
visible hematuria <60mL/min, ACR >30, PCR >50

Chronic kidney disease (CKD)

Definition

Is defined as irreversible, substantial and long standing loss of renal function

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Presentation

There is poor correlation between symptoms and severity of renal disease

Progression may be insidious that patients attribute symptoms to age or a
minor illness

Referral

Referral to renal services is based on local guidelines, but as a general rule refer if
CKD stage 3 or more, ie GFR <60mL/min, if other features are present

GFR is falling progressively

Non visible microscopic hematuria
Urine protein creatinine ratio (PCR) increases
Unexplained anemia, hyperkalemia, or calcium or phosphate imbalance
Suspected systemic illness (eg SLE)
BP uncontrolled despite taking 3 drugs
Refer urgently if GFR 15-29 (same-day if <15) even if no other features present

Silence

Serious renal failure may cause no symptoms at all; this is why we check U&Es
before surgery and other major intervention

Do not dismiss odd chronic symptoms such as fatigue without considering checking
renal function

Microalbuminuria

Microalbuminuria is a silent harbinger of serious renal and cardiovascular risk

In one study, 30% of those with type 2 DM died within 5yrs of developing
microalbuminuria
This is partly prevented by use of ACE-i

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Urine

Perform dipstick urine analysis whenever you suspect renal disease

Proteinuria

Consensus is now to avoid 24hr collections (costly, inaccurate) and use

albumin:creatinine ratio (ACR) or protein:creatinine ratio (PCR) on a random
urine sample, ideally an early morning sample as this avoids orthostatic
proteinuria

ACR is preferred to PCR, especially in diabetics

Normal values

Normal ACR is <2.5 (men)

Normal ACR is <3.5 (women)
Transient rises <5 can occur with fever or exercise

Causes of raised ACR/PCR

Glomerular or tubular disease (eg nephrotic syndrome)

Diabetes mellitus
Amyloidosis
Hypertension
Interstitial nephritis
Heavy metals
Multiple myeloma
Pregnancy and contraceptive pills

Causes of microalbuminuria (albumin excretion 30-300mg/24hr)

Diabetes mellitus
Hypertension
Minimal change GN

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Hematuria

Blood in the urine may arise from anywhere in the renal tract

It is classified as

Visible hematuria (VH) previously known as macroscopic, frank hematuria

Non visible hematuria (NVH) found in dipstick or microscopy

NVH is classified as

Symptomatic (sNVH) with dysuria, hesitancy, urgency

Asymptomatic (aNVH)

Patient with one episode of VH, one of sNVH or persistent aNVH require
further assessment

Exclude transient causes (UTI, vigorous exercise, menstruation)

Check creatinine/eGFR, proteinuria (spot ACR or PCR) and BP
Painless VH usually means bladder cancer (refer urgently)
In aNVH or if systemic symptoms, consider FBC, ESR, CRP, blood film,
clotting (NB do not simply attribute hematuria to anticoagulant/antiplatelet
agents)
Urine microscopy, culture and sensitivity to look for infection,
malignant/inflammatory cells, casts, crystals
Ultrasound scan and rapid referral to nephrology if rapid decline in GFR
or hematuria with proteinuria, casts or dysmorphic cells. Red cell casts =
glomerular bleeding

All others should be monitored in primary care with annual review of urine dip, BP,
eGFR and proteinuria (ACR/PCR); refer if above features appear.

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Causes of hematuria

Renal causes

Neoplasia, glomerulonephritis (often IgA nephropathy), interstitial nephritis,

polycystic kidney disease, papillary necrosis, infection (pyelonephritis), trauma.

Extrarenal causes

Calculi, infection, neoplasia, trauma (eg from catheter)

Some drugs can cause haematuria

eg, captopril, cephalosporins, ciprooxacin, furosemide, NSAIDS.

Imaging

Abdominal X-ray (AXR)

Is no longer used for primary assessment of stones

CT kidney + ureter + bladder (CTKUB)

CTKUB is the 1st choice investigation

NB Not all women with recurrent UTI + haematuria need cystoscopy, but have a good
reason not to (Reynards rule).

Other findings

Glucose DM, pregnancy, sepsis, renal tubular damage.

Ketones Starvation, ketoacidosis.

Leucocytes UTI, vaginal discharge.

Nitrites UTI, high-protein meal.

Bilirubin Obstructive jaundice.

Urobilinogen Pre-hepatic jaundice.

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Specic gravity Normal range (NR): 1.0001.030.

pH NR: 4.58.

Urinalysis

Urine specific gravity (SG)

Causes of low SG (<1003)

Diabetes insipidus
Renal impairment

Causes of high SG (>1025)

Diabetes mellitus
Adrenal insufficiency
Liver disease
Heart failure
Acute water loss

Source of error in interpreting dipstick results

Bilirubin

False +ve phenothiazines

False ve urine not fresh, rifampicin

Urobilinogen

Normally present in urine due to metabolism of bilirubin in the gut by bacteria

and subsequent absorption
False ve urine not fresh
Excess may give a false +ve test for prophobilinogen

Ketones

False +ve L-dopa

False ve 3-hydroxybutyrate

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Blood

False +ve hemoglobinuria, dehydration, myoglobinuria, porphyria,

phenidione, phenolphthalein, or contamination with menstrual blood
False ve low urinary pH, air exposed dipstick

Urine glucose

False +ve peroxide, chlorine

False ve ascorbic acid, salicylate, L-dopa

Protein

False +ve urine pH >7.5, concentrated urine, frank hematuria, presence of

penicillin, sulphonamides, pus, semen or vaginal secretion
False ve dilute urine, non-albumin urinary protein

White cells

White cells >10/mm3 in an unspun specimen is abnormal, often from UTI

Red cells

Red cells >2/mm3 is abnormal

Casts

Casts are cylindrical bodies formed in the lumen of distal tubules, and can be
waxy, granular, hyaline or cellular

Crystals

Crystals are common in old or cold urine and may not signify pathology.
They are important in stone formers.

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Urinary tract infection (UTI)

Denitions

Bacteriuria Bacteria in the urine; may be asymptomatic or symptomatic.

UTI The presence of a pure growth of >105 organisms per mL of fresh
midstream urine (MSU)
Lower UTI Urethra (urethritis), bladder (cystitis), prostate (prostatitis)
Upper UTI Renal pelvis (pyelonephritis)

Up to a third of women with symptoms have negative MSU (= abacterial cystitis or

the urethral syndrome).

Classication

Uncomplicated UTIs (normal renal tract + function)

Complicated (abnormal renal/GU tract, voiding difficulty/obstruction, renal
function, impaired host defences, virulent organism, eg Staph. aureus)

Risk factors

Females, sexual intercourse, exposure to spermicide in female (by diaphragm or

condoms), pregnancy, menopause
host defence (immunosuppression, DM)
Urinary tract obstruction (stones, catheter, malformation)

In pregnancy, UTI is common and often asymptomatic, until serious pyelonephritis

or premature delivery ( fetal death) supervenes, so do routine dipstick in
pregnancy.

Urine in catheterized bladders is almost always infected (CSUs and treatment are
pointless unless the patient is ill)

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Complications of UTI requiring ICU admission can include

Pyelonephritis
Urosepsis with bacteremia
Suppurative infections

Organisms

Gram-negative bacteria are most commonly isolated in UTI

Escherichia coli is the most common single cause

Other Enterobacteriaceae (Klebsiella, Citrobacter, Enterobacter, Serratia) are
also frequently isolated.
Pseudomonas, Providencia, and Proteus sp. are common catheter associated
organisms.

Gram-positive bacteria can sometimes cause UTI

Staphylococcus aureus can be seen in the setting of bacteremia (extra-renal

sources should be considered)
Enterococci (including vancomycin-resistant enterococci [VRE] ) and non
aureus staphylococci can be seen in the elderly or in patients with structural
abnormalities or indwelling catheters.

Candida species

Candida species can cause UTI and occasionally ascending infection and
fungemia.

Symptoms

Acute pyelonephritis

High fever, rigors, vomiting, loin pain and tenderness, oliguria (if acute kidney
injury).

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Cystitis

Frequency, dysuria, urgency, haematuria, suprapubic pain.

Prostatitis

Flu-like symptoms, low backache, few urinary symptoms, swollen or tender

prostate on PR.

Signs

Fever, abdominal or loin tenderness, foul-smelling urine.

Occasionally distended bladder, enlarged prostate

Investigations

Urinalysis

Urinary white blood cell count >5 cells per high-powered field is suggestive
of infection, but is not diagnostic.
Chronically catheterized patients may have chronic pyuria in the absence of
infection.

Urine culture

Urine culture identifies the pathogen and provides antimicrobial susceptibilities

to allow narrowing of therapy.
Culture of >100,000 colony-forming units of a single species is suggestive of
infection, but is also not diagnostic.
In symptomatic individuals with pyuria, lower bacterial counts should not be
disregarded.
Urine should be collected from the urine port, not the drainage bag.
In chronically catheterized patients, a sample from a newly placed catheter is
helpful.
Sampling should include nephrostomy tube, if present.

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Blood tests

FBC, U&E, CRP

Consider fasting glucose and PSA (wait 6months, as UTI cause false +ve)

Blood cultures

Blood cultures should be drawn before antibiotics in any patient with signs of
developing sepsis or suspicion of pyelonephritis

Imaging

Imaging (renal ultrasound or computed tomography [CT] scan) should be

performed if patient fails to improve promptly.

Causes of sterile pyuria

TB
Treated UTI <2 weeks prior
UTI with oversensitive culture requirement
Inadequately treated UTI
Papillary necrosis (eg DM or analgesic excess)
Appendicitis
Tubulointerstitial nephritis
Calculi, prostatitis
Polycystic kidney
Bladder tumour
Chemical cystitis (eg cyclophosphamide)

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Features of genitourinary tuberculosis

None is specic, so have a high index of suspicion in

Sterile pyuria
Those with risk factors (esp. if HIV+ve)
Look for a high ESR/CRP
Ask about past lung TB (but often there is no history).

Genitourinary symptoms

Dysuria (eg in 50% of those with prostate TB)

Flank pain (59%; a cold abscess in the ank is a rare presentation)
Perineal pain (40%)
Mycobacteriuria 38% (early-morning sample)
Scrotal stula 12%
Leucocytes in urine 85%, (sterile pyuria); (78% in prostatic secretions)
Haematuria in 53%

Prevention of UTI

Drink more water

Antibiotic prophylaxis, (continuously or post-coital) UTI rates in females
with many UTIs
Self-treatment with a single antibiotic dose as symptoms start is an option.
Drinking 200750mL of cranberry or lingo berry juice a day, or taking
cranberry concentrate tablets, risk of symptomatic recurrent infection in
women by 1020% (may inhibit adherence of bacteria to bladder uroepithelial
cells; avoid if taking warfarin)
There is no evidence that post-coital voiding, or pre-voiding, or advice on
wiping patterns in females is of benet

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Managing UTI

Drink plenty of uids; urinate often (do not hold on)

Management of bacterial UTI in adult non-pregnant women

Consider empirical treatment for presumed E. coli in other healthy women who
present with lower UTI

Consider trimethoprim 200mg/12h PO or nitrofurantoin 50mg/6h PO for 36d (if

normal renal function), amoxicillin 500mg/8h PO.

Alternative

Cefalexin 1g/12h (if eGFR >40)

2nd line

Co-amoxiclav PO (7d course).

In case of vaginal itch or discharge consider vaginal examination and swabs for
other diagnoses, eg thrush, chlamydia, other STIs.

In non-pregnant women with upper UTI

Take a urine culture

Treat with, eg co-amoxiclav 1.2g/8h IV, then oral when afebrile, complete 7d
course.
Avoid nitrofurantroin
Resistance to trimethoprim is common

Non-pregnant women with asymptomatic bacteriuria do not need antibiotics so

screening is not recommended.

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Managing bacterial UTI in pregnant women

Get expert help

Any bacteriuria (symptomatic or asymptomatic) should be treated with an
antibiotic.
Dipstick and urine culture should be repeated at each antenatal visit

Managing bacterial UTI in adult men

Take UTI in men seriously as it often results from an anatomical or functional

anomaly, therefore, all men with symptoms of upper UTI, recurrent UTI or who fail to
respond to antibiotic therapy should be referred to urologist.

Also consider prostatitis, epididymitis and chlamydial infection.

Bacterial UTI in men may need a 2wk course of a quinolone, such as levooxacin
(if no response, think of prostatitis and treat for 4wks).

Antibiotic therapy of asymptomatic bacteriuria in elderly men (>65yrs old) is not

recommended, as it does not reduce morbidity or mortality while it increases the risk
of adverse events such as rashes or GI problems

Managing UTI in ICU setting

Bacterial UTI

Obtain blood and urine cultures before empiric antibiotics

Renal dosing adjustments are required with most antibiotics

Empiric treatment of suspected gram-negative septic shock or urosepsis

consists of

Dual therapy with a -lactam (extended spectrum penicillin, third- or

fourth-generation cephalosporin, carbapenem) plus an aminoglycoside (or
a quinolone in settings where resistance to quinolones does not exceed 10%)
in critically ill patients.

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 Monotherapy (-lactam or aminoglycoside) may be utilized for less severe
infections without recent antibiotic use. Quinolone monotherapy can be
considered in areas where quinolone resistance is <10%.
Alternatives for coverage of gram-negative in patients with -lactam allergies
include aztreonam, quinolones, and aminoglycosides.

Enterococci

If enterococci are suspected, ampicillin or vancomycin should be added.

In patients known to be colonized with VRE, linezolid should be considered.

Antibiotic spectrum should be narrowed once sensitivities are available.

Therapy may be switched from parenteral to oral antibiotics once the fever resolves

Duration of antibiotics for a severe UTI requiring ICU admission is generally 2wk

Catheter-associated UTI, which develops in the ICU setting and responds promptly
to therapy, may be treated for 7d

Candida UTI

Removal of urinary catheter may result in spontaneous clearance.

Candiduria in the setting of neutropenia or urinary tract surgical procedures

generally requires treatment, even if asymptomatic.

In other patients, treatment should be reserved for symptomatic infections.

Fluconazole is the drug of choice due to excellent urinary concentrations.

Amphorericin B, flucytosine, or echinocandins may be used for fluconazole-

resistant Candida species

In catheterized patients candiduria frequently recurs

Placement of new catheter or a temporary intermittent catheterization may

decrease colonization.
Amphotericin B bladder washes result in transient clearing of candiduria

Dr. Ali Ragab 21

Prevention of catheter associated UTI.

Minimize the duration of catheterization

Meatal care and/or topical antimicrobials are not effective
Minimize trauma
Avoid elevation of drainage bag

Acute kidney injury

Definition

Acute kidney injury (AKI), previously known as acute renal failure (ARF) is
characterized by a sudden decline in kidney function.

Most important features are azotemia (accumulation of nitrogenous waste products,

e.g., urea and creatinine) and oliguria (decrease in urine output to <500mL/day).

RIFLE (Risk Injury Failure Loss End stage) classification for AKI

GFR criteria Urine output criteria

Risk Increased SCreat 1.5 UO <0.5mL/kg/h 6h
or GFR decrease > 25%
Injury Increased SCreat 2 UO <0.5mL/kg/h 12h
or GFR decrease > 50%
Failure Increased SCreat 3 UO <0.3mL/kg/h 24h
GFR decrease 75% or anuria 12 h
or SCreat 4mg/dL
Acute rise 0.5mg/dL
Loss Persistent ARF = complete loss of kidney function >4 weeks
ESKD End stage kidney disease (>3 months)

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Risk factors for developing AKI

Age >75yrs
Chronic kidney disease
Cardiac failure
Peripheral vascular disease
Chronic liver disease
Diabetes
Drugs (esp newly started)
Sepsis
Poor uid intake/increased losses
History of urinary symptoms

Causes

Commonest are ischaemia, sepsis and nephrotoxins, although prostatic disease

causes up to 25% in some studies and has the best prognosis

Pre-renal (4070%)

Due to renal hypoperfusion, eg hypotension (any cause, including hypovolaemia,

sepsis), renal artery stenosis ACE-i.

Intrinsic renal (1050%)

Tubular

Acute tubular necrosis (ATN) is the commonest cause of AKI, often a result of

pre-renal damage
Nephrotoxins such as drugs (eg aminoglycosides)
Radiological contrast
Myoglobinuria in rhabdomyolysis.
Also crystal damage (eg ethylene glycol poisoning, uric acid), myeloma, Ca2+

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Glomerular

Autoimmune such as SLE, HSP

Drugs
Infections
Primary glomerulonephritides

Interstitial

Drugs
Inltration with, eg lymphoma
Infection
Tumour lysis syndrome following chemotherapy

Vascular

Vasculitis
Malignant BP
Thrombus or cholesterol emboli
HUS/TTP
Large vessel occlusion, eg dissection or thrombus

Post-renal (1025%)

Caused by urinary tract obstruction:

Luminal

Stones, clots, sloughed papillae

Mural

Malignancy (eg ureteric, bladder, prostate), BPH, strictures

Extrinsic compression

Malignancy (esp pelvic), retroperitoneal brosis.

Dr. Ali Ragab 24

Drugs that may contribute to AKI

Radiocontrast agents
Aminoglycosides
Amphotericin
Non-steroidal anti-inflammatory drugs
-lactam antibiotics (interstitial nephropathy)
Sulfonamides
Aciclovir (acyclovir)
Methotrexate
Cisplatin
Cyclosporin A
Tacrolimus
Sirolimus (rapamycin)
Starch solutions

Investigations

Urinalysis

Urine microscopy

Dysmorphic RBC or RBC casts (glomerulonephritis)

WBC casts (acute interstitial nephritis [AIN], pyelonephritis)
Eosinophils (AIN)
Fatty casts (nephrotic syndrome)
Muddy brown or coarse granular casts (ATN)

Urinary sodium

Urine sodium (UNa) <20 mEq/L suggests pre-renal azotemia

UNa >40 mEq/L suggests intrinsic cause

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Fractional excretion of sodium (FENa)

FENa = (UNa/plasma Na)/ (Urine creatinine/plasma creatinine) x100%

Less than 1 % suggests prerenal azotemia.

More than 1% suggests intrinsic causes
May be falsely elevated in setting of diuretic use

Fractional excretion of urea (FEUrea)

FEUrea = (urine urea/plasma urea)/ (urine creatinine/plasma creatinine) x100%

Unaffected by diuretic
Typically <35% in prerenal azotemia.

Serum chemistry studies

Electrolyte and acid-base abnormalities

Hyponatremia/hypernatremia.
Hyperkalemia/hypokalemia.
Metabolic acidosis

Complete blood count (CBC)

Anemia (multiple myeloma, TTP/HUS, CKD)

Thrombocytopenia (TTP/HUS)
WBC differential (eosinophilia suggests AIN, atheroemboli)

Serologic tests

ANA and anti-dsDNA (SLE)

Antineutrophil cytoplasmic antibody (ANCA) (vasculitis)
Hepatitis serologies (polyarteritis nodosa, glomerulonephritis)
Anti-GBM (Goodpasture syndrome)
Cryoglobulins, complement levels (postinfectious glomerulonephritis, SLE)

Dr. Ali Ragab 26

Radiologic studies

Renal ultrasound

Noninvasive and rapid, can assess renal parenchyma and collecting systems
Sensitive for urinary obstruction.
Small renal size and increased cortical echogenicity suggest CKD
Post void bladder ultrasound, assess bladder emptying.

Renal duplex

Screen for renovascular disease and renal vein thrombosis.

Computed tomography

Consider risk/benefits before use of radiocontrast in patients with AKI

CTKUB (does not require contrast), which can show obstructing masses or
calculi

Retrograde pyelography

Consider if urinary tract obstruction suspected.

Radionuclide renal scan

Assess renal perfusion as well as function.

Renal arteriogram

Consider if renal artery thrombus suspected

Magnetic resonance imaging (MRI)

Consider risks/benefits before use of gadolinium due to risk of nephrogenic

systemic fibrosis (NSF)
NSF risk may be reduced with postexposure hemodialysis.

Dr. Ali Ragab 27

Renal biopsy

Consider if other studies do not identify cause of AKI

If confirmation of diagnosis needed before initiation of specialized treatment
such as immunosuppressive medication, or if prognostic information needed.

Novel biomarkers in AKI

These biomarkers appear to change significantly earlier than changes in serum

creatinine.
Cystatin C appears to reflects changes in glomerular filtration rate
Neutrophil gelatinase-associated lipocalin (NGAL) appears to reflect
tubular stress/injury
They also appear to dynamically change with treatment or recovery, which
suggests that they can be used to monitor interventions.
They may identify subpopulations of patients who do not have AKI according to
creatinine based criteria, but actually have a degree of kidney stress/injury
that can be detected by biomarkers

Is the injury acute or the damage chronic?

Suspect chronic if small kidneys (<9cm) on USS, anaemia, low Ca2+, high PO4

But the only denite sign of chronic disease is previous blood results showing high
creatinine/low GFR.

When to refer to a nephrologist (and what they would like to know)

Firstly assess the patient, correct pre- and post-renal factors, and treat urgent
problems such as hyperkalaemia and pulmonary oedema.

Always refer

Hyperkalaemia in an oligoanuric patient

Fluid overload unresponsive to medical treatment
Urea >40mmol/L signs of uraemia such as pericarditis
Patients with suspected glomerulonephritis

Dr. Ali Ragab 28

Consider referral

No obvious reversible cause, creatinine >300 or rising >50mol/L per day.

What they want to know

The history and time course

U&E results (esp K+)
Urine dipstick
Drugs
Fluid balance and current volume status

Indications for dialysis (RRT) (discuss with a nephrologist EARLY)

Refractory pulmonary oedema

Persistent hyperkalaemia (K+ >7mmol/L)
Severe metabolic acidosis (pH<7.2 or base excess <10)
Uraemic complications such as encephalopathy or Uraemic pericarditis
(pericardial rub)
Drug overdose BLAST (Barbituates, Lithium, Alcohol (and ethylene glycol),
Salicylates, Theophyline)

Management of AKI

General measures

Assess volume status

Look for urine volume, non-visible JVP, poor tissue turgor, BP, pulse.
Signs of uid overload: BP, JVP, lung crepitations, peripheral oedema,
gallop rhythm on cardiac auscultation

Dr. Ali Ragab 29

Aim for euvolaemia

Maintain mean arterial pressure (MAP) >60-70mmHg

Maintain (CVP) 8-12 cmH2O
If difficult balance with risk of uid overload, consider titrating input hourly, by
matching previous hours output +25mL/h for insensible losses
If euvolaemic review balance over 24-hour period aim to match input to loss
(urine, vomit, diarrhoea, drains) +500mL for insensible loss (more if T )

Avoid K+ containing uids unless hypokalaemic.

Stop nephrotoxic drugs

Stop nephrotoxic drugs eg NSAIDS, ACE inhibitor, gentamicin, amphotericin.

Stop metformin if creatinine is >150mmol/L
Check and adjust doses of renally excreted drugs

Monitoring

Check pulse, BP, JVP, and urine output hourly (insert a urinary catheter)
Consider inserting a CVP line if on HDU/ICU.
Daily U&Es
Daily uid balance chart and daily weight.

Nutrition

Nutrition is vital in the critically unwell patient, aim for normal calorie intake
(more if catabolism , eg burns, sepsis) and protein 0.5g/kg/d.
If oral intake is poor, consider nasogastric nutrition early (parenteral if NG
impossible)

Dr. Ali Ragab 30

Treat underlying cause

Pre-renal

Correct volume depletion with appropriate uids

Treat sepsis with antibiotics
Consider inotropic support if signs of shock

Post-renal

Catheterize and consider CT of renal tract (CTKUB) and urology referral if

obstruction likely cause.
If signs of obstruction and hydronephrosis on CT/USS then discuss with
urology regarding cystoscopy and retrograde stents or nephrostomy insertion;
this buys time to allow treatment of cause of obstruction, eg stone, mass.

Intrinsic renal

Refer early to nephrology if concern over tubulointerstitial or glomerular

pathology, any signs of systemic disease, multi-organ involvement (eg
pulmonary-renal, hepatorenal syndromes) or indications for dialysis

Management of selected syndromes

Hepatorenal syndrome

AKI in advanced liver disease, unresponsive to volume resuscitation

Often precipitated by

Gastrointestinal bleeding, infection, diuresis, and large volume

paracentesis (especially if done without concomitant albumin infusion)

May be reversible with improvement in liver function or liver transplantation

Dr. Ali Ragab 31

Management

Midodrine (5-10mg tid) in combination with octreotide (up to 250g SC bid)

Consider salt poor albumin infusions (1mg/kg/d up to a maximum of 100
mg/d for 48 h)

Cardiorenal syndrome

Impaired renal perfusion due to low cardiac output

Management

Treat underlying heart failure.

Dialytic support if significant volume overload or poorly responsive to diuretics

TTP and HUS

Characterized by

MicroAngiopathic Hemolytic Anemia (MAHA)

Thrombocytopenia
AKI

TTP in addition, presents with fluctuating neurologic symptoms and fever.

Causative factors

Infection with Escherichia coli

Drug induced (quinine, mitomycin, cisplatin, antiplatelet agents, etc.)
Idiopathic

Management

Plasma exchange

Dr. Ali Ragab 32

Scleroderma renal crisis

AKI with symptoms of malignant hypertension

Occurs in 10%-20% of patients with systemic sclerosis

Pathology

Onion skin hypertrophy

Intimal hyperplasia of interlobular and glomerular vessels.

Urine sediment typically bland

Management

ACE inhibitors; steroids contraindicated

Acute interstitial nephritis (AIN)

Inflammation of the renal interstitium and tubules

Often drug induced

Features of allergy fever, rash, and eosinophilia (may be absent if NSAID induced)

Treatment

If no improvement after drug withdrawal, consider prednisone 1mg/kg/d for

at least 1-2 wk (maximum of 40-60 mg/d), then taper gradually if serum
creatinine is improving.
Complete total course of 2-3mo.

Myoglobinuric AKI

Definition

AKI in setting of extensive myoglobin release from skeletal muscle injury

(rhabdomyolysis)

Dr. Ali Ragab 33

Investigations

Serum creatinine phosphokinase >10,000

Urine dipstick strongly positive for blood without RBCs in urine sediment

Management

0.9% saline

Volume expansion with 0.9% saline to maintain urine output 250-300 mL/h

Bicarbonate infusion

Consider IV bicarbonate infusion (e.g., three ampules of bicarbonate in 1L of 5%

dextrose in water) in non-oliguric patients to keep urinary pH >6.5 with close
monitoring to prevent hypocalcemia or metabolic alkalosis.

Diuretics

Give diuretics if volume overload develops.

Tumor lysis syndrome

Diffuse nephronal microobstruction by released intracellular contents

(phosphates, uric acid, purine metabolites) in setting of rapid cell death

Diagnosis

High phosphorus, LDH, uric acid, potassium, and hypocalcemia

Common precipitants

Chemotherapy induction for hematologic and lymphoproliferative malignancies

with large tumor burdens or for tumors with rapid cell turnover

Dr. Ali Ragab 34

Management

Volume expansion before chemotherapy and diuresis

Pretreatment with allopurinol or rasburicase (recombinant urate oxidase
enzyme) to prevent acute urate toxicity

Radiocontrast induced nephropathy

AKI develops with in 24 h of radiocontrast exposure, peaks by 72h, and improves over
4-7d.

Risk factors

Preexisting renal insufficiency

Volume depletion

Preventive measures

Normal saline (1mL/kg/h) starting 2-6 h before the procedure and to continue
for 6h afterward or Isotonic bicarbonate (150mEq NaHCO3 1L D5W) infuse
at 3 ml/kg/hr one hour before the procedure, then 1 ml/kg/hr for 6 hrs after the
procedure
N-acetylcysteine 600-1200mg every 12h orally for two doses, before and after
the procedure
Use nonionic, low osmolality radiocontrast and minimize contrast volume.

Manage complications

Hyperkalemia

ECG changes (in order)

Tall tented T waves

Small or absent P wave
Increased PR interval
Widened QRS complex (sine wave pattern)
Asystole

Dr. Ali Ragab 35

Immediate treatment

Calcium gluconate

10mL of 10% calcium gluconate IV via a big vein over 2min, repeated as
necessary until ECG improves.
This is cardioprotective but does not affect K+ level.

Insulin glucose

Dose of 10units actrapid in 50mL 20% glucose

Insulin stimulates intracellular uptake of K+, lowering serum K+ by 12mmol/L
over 60min.

Salbutamol nebulizers

Salbutamol nebulizers work in the same way as insulin/glucose but high doses
are required (1020mg) and tachycardia can limit use.

Bicarbonate

If venous bicarbonate low (ie acidotic) giving IV sodium bicarbonate (50mL of

8.4% NaHCO3 as an infusion or bolus into a big vein) can help to drive K+ into
cells, the effect is unpredictable.

All of these measures are temporary and only buy time to denitively lower K+, via
either renal clearance (eg relieving obstruction with catheter or correcting prerenal
failure with uids) or haemodialysis/ltration if the patient is oligoanuric.

Dr. Ali Ragab 36

Pulmonary edema

Management

Sit up and give high ow O2

Venous vasodilator, eg diamorphine 2.5mg IV (+ antiemetic, eg cyclizine
50mg IV)
Furosemide 80250mg IV either as IVI over 1h or boluses titrated to response
(larger doses are needed in renal failure)
If no response, urgent haemodialysis or haemoltration is needed
Consider continuous positive airway pressure ventilation (CPAP)
IV nitrates also have a role

Renal replacement therapy

Options in AKI include haemodialysis and haemoltration, both require large-

bore venous access (eg internal jugular line).

Dr. Ali Ragab 37

Chronic kidney disease (CKD)

Denitions

Impaired renal function for >3 months based on abnormal structure or function
GFR <60mL/min/1.73m2 for >3 months with or without evidence of kidney
damage
End-stage renal failure (ESRF) is dened as GFR <15mL/min/1.73m2 or need for
renal replacement therapy

Causes

Diabetes (type II > type I)

Glomerulonephritis (IgA nephropathy, mesangiocapillary GN, systemic
disorders, SLE, vasculitis)
Hypertension or renovascular disease
Pyelonephritis and reux nephropathy
Unknown (have no obvious cause of CKD, many of these present late with
small, shrunken kidneys where a biopsy would be uninformative)
Obstructive uropathy, which commonly causes AKI but is often reversible
Chronic interstitial nephritis (eg myeloma, amyloid)
Adult polycystic kidney disease (APKD) is the commonest inherited cause of
CKD
Rare inherited disorders include Alports syndrome and Fabrys disease

Symptoms and signs of chronic kidney disease

Central nervous system

Confusion, coma, fits (severe uraemia)

Dr. Ali Ragab 38

Cardiovascular system

Uraemic pericarditis
Hypertension
Peripheral vascular disease
Heart failure

Renal

Nocturia
Polyuria
Salt and water retention
Oedema

Renal osteodystrophy

Osteomalacia
Muscle weakness
Bone pain
Hyperparathyroidism
Osteosclerosis
Adynamic bone disease

Anaemia

Pallor
Lethargy
Breathlessness on exercise

Platelet abnormality

Epistaxis
Bruising

Dr. Ali Ragab 39

Skin

Pigmentation
Pruritus

GI tract

Anorexia
Nausea
Vomiting
Diarrhoea

Endocrine/gonads

Amenorrhoea
Erectile dysfunction
Infertility

Polyneuropathy

Investigation

Urinalysis

Haematuria

Haematuria may indicate glomerulonephritis, but other sources must be

excluded
Haematuria should not be assumed to be due to the presence of an indwelling
catheter

Proteinuria

Proteinuria, if heavy, is strongly suggestive of glomerular disease.

Urinary infection may also cause proteinuria.

Glycosuria

Glycosuria with normal blood glucose is common in CKD.

Dr. Ali Ragab 40

Urine culture

Urine culture, including early-morning urine samples for TB

Urine microscopy

White cells

White cells in the urine usually indicate active bacterial urinary infection
Sterile pyuria suggests papillary necrosis or renal tuberculosis.

Eosinophiluria

Eosinophiluria is strongly suggestive of allergic tubulointerstitial nephritis

or cholesterol embolization.

Casts

Granular casts are formed from abnormal cells within the tubular lumen, and
indicate active renal disease.
Red-cell casts are highly suggestive of glomerulonephritis.
Red cells in the urine may be from anywhere between the glomerulus and the
urethral meatus

Albumin:creatinine ratio or protein:creatinine ratio

Blood

Hb (normochromic, normocytic anaemia)

ESR
Kidney function tests
Glucose (DM)
Electrolytes ( Ca2+, PO4)
Renal osteodystrophy (alk phos)
PTH (increased if CKD stage 3)

Dr. Ali Ragab 41

Imaging

Ultrasound scan

USS to check size, anatomy and corticomedullary differentiation

In CKD kidneys are usually small (<9cm)
Enlarged in inltrative disorders (amyloid, myeloma), APKD and DM.
If asymmetrical consider MAG3 renogram to look at contribution of each
kidney to overall function.

Immunology

Complement components may be low in

Active renal disease due to SLE

Mesangiocapillary glomerulonephritis
Post-streptococcal glomerulonephritis
Cryoglobulinaemia

Autoantibody screening is useful in detection of

SLE, scleroderma, Wegeners granulomatosis and microscopic polyangiitis and

Goodpastures syndrome

Cryoglobulins

Cryoglobulins in unexplained glomerular disease, particularly

mesangiocapillary glomerulonephritis.

Antibodies to streptococcal antigens

(antistreptolysin O titre (ASOT), anti-DNAse B) if post-streptococcal

glomerulonephritis is possible.

Dr. Ali Ragab 42

Antibodies to hepatitis B and C

Polyarteritis or membranous nephropathy (hepatitis B)

Cryoglobulinaemic renal disease (hepatitis C).

Antibodies to HIV

Antibodies to HIV raise the possibility of HIV-associated renal disease.

Histology

Consider renal biopsy if rapidly progressive disease or unclear cause and normal
sized kidneys.

Classifying renal impairment in chronic kidney disease

Stage GFR (mL/min) Notes

1 >90 Normal or GFR with other evidence of renal damage
2 6089 Slight GFR with other evidence of renal damage
3A 4559 Moderate GFR with or without evidence of other renal
3B 3044 damage
4 1529 Severe GFR with or without evidence of renal damage
5 <15 Established renal failure

One reason to classify renal impairment is to motivate secondary prevention, eg to

mandate ACE-i or ARB if BP >140/85 especially if proteinuria is present or stage 3

Criteria for referral of chronic kidney disease patients to a nephrologist

Stage 4 and 5 CKD

Significant proteinuria (PCR >100mg/mmol or ACR >70mg/mmol)
Proteinuria with haematuria
Rapidly falling eGFR (>5mL/min in 1yr, or >10mL/min within 5yrs)
BP poorly controlled despite 4 antihypertensive drugs at therapeutic doses
Known or suspected rare or genetic causes of CKD
Suspected renal artery stenosis

Dr. Ali Ragab 43

Treatment

Goals of treatment

BP <120/80
Proteinuria <0.3 g/24h

Patients with chronic kidney disease and proteinuria >1g/24 h

ACE-i increasing to maximum dose

Add angiotensin receptor antagonist if goals are not achieved
Add diuretic to prevent hyperkalaemia and help to control BP
Add calcium-channel blocker (verapamil or diltiazem) if goals not achieved

Additional measures

Statins to lower cholesterol to <4.5 mmol/L

Stop smoking (three-fold higher rate of deterioration in CKD)
Treat diabetes (HbA1c <7%)
Normal protein diet (0.81 g/kg)

Management of patients can be split into four main approaches

Identifying and treating reversible causes

Relieve obstruction
Stop nephrotoxic drugs
Deal with high Ca2+
Deal with cardiovascular risk (stop smoking, achieve a healthy weight)
Tight glucose control in DM

Dr. Ali Ragab 44

Limiting progression/complications

Blood pressure

Even a small BP drop may save signicant renal function

Target BP is <130/80 (<125/75 if diabetic or ACR >70)
In diabetic kidney disease, even with normal BP, treat with an ACE-i or ARB

Renal bone disease

Check PTH and treat if raised

PO43 rises in CKD, which PTH further

Managing hyperphosphatemia

Restrict diet
Give binders (eg Calcichew) to gut absorption

Vitamin D and Calcium supplements

Vit D analogues (eg alfacalcidol) and Ca2+ supplements bone disease and
hyperparathyroidism

Cardiovascular modication

In CKD stages 1 and 2, risk from cardiovascular death is higher than the risk of
reaching ESRF
Give statins to CKD patients with raised lipids as per guidelines for any patient.
Give aspirin also (CKD is not a contraindication to the use of low-dose aspirin,
but beware of risk of bleeding).

Diet

Healthy moderate protein diet

K+ restriction if hyperkalaemic
Avoidance of high phosphate foods (eg milk, cheese, eggs)

Dr. Ali Ragab 45

Symptom control

Anaemia

Replace iron/B12/folate if necessary.

If still anaemic consider recombinant human erythropoietin.
If Hb falls despite this, and no infection, haemolysis, or blood loss, etc. suspect
red cell aplasia (anti-epo antibodies). Stop at once and get help from
haematology.
Keep Hb 100120g/L; above this risks IV access thrombosis, BP, MI

Acidosis

Consider sodium bicarbonate supplements for patients with low serum

bicarbonate; this not only improves symptoms but may slow progression of
CKD.
Caution in patients with hypertension, as sodium load can BP

Oedema

High doses of loop diuretics may be needed (eg furosemide 250mg2g/24h

metolazone 510mg/24h PO each morning)
Restriction on uid and sodium intake.

Restless legs/cramps

Check ferritin (low levels worsen symptoms), clonazepam (0.52mg daily) or

gabapentin may help.
Quinine sulfate can help with cramps.

Preparation for renal replacement therapy (RRT)

Dr. Ali Ragab 46

Renal biopsy

Indications for renal biopsy

Unexplained acute kidney injury

Unexplained chronic kidney disease
Acute nephritic syndromes
Unexplained proteinuria and haematuria
Systemic diseases associated with kidney dysfunction
Suspected transplant rejection
To guide treatment

Pre-procedure

Check FBC, clotting, group and save.

The physician performing the procedure should obtain written informed
consent.
Ultrasound to delineate anatomy.
Stop anticoagulants (aspirin 1wk, warfarin 23d, LMWH 24h)

Contraindications

Abnormal clotting
Hypertension >160/90mmHg
Single kidney (except for renal transplants)
Chronic kidney disease with small kidneys (<9cm)
Uncooperative patient
Horseshoe kidney
Renal neoplasms

Dr. Ali Ragab 47

Post procedure

Bed rest for a minimum of 6h

Monitor pulse, BP, symptoms, and urine colour
Bleeding is the main complication; most occurs within 8h, although it may be
delayed by up to 72h.
Macroscopic haematuria occurs and blood transfusion may be needed
Aspirin or warfarin can be restarted the next day if procedure uncomplicated.

Renal replacement therapy (RRT) dialysis

Dialytic therapy or renal replacement therapy (RRT) is essential for management of

patients with end stage renal disease (ESRD) and can be helpful for managing acute
kidney injury (AKI) and toxic ingestions

Mechanisms of solute, toxins, and fluid removal

Diffusion

Solute or water moves from an area of high concentration (blood) to an area of

low concentration (dialysate) through the dialyzer membrane
Diffusion is affected by concentration gradient, solute characteristics
(molecular size and charge), dialyzer membrane characteristics (surface area,
porosity, and thickness), and flow rate of blood and dialysate

Convection

Solutes and water are forced across the dialyzer membrane by hydrostatic
pressure
Filtrate has essentially the same chemical composition as plasma.
Convection is most important for volume removal and hemofiltration

Dr. Ali Ragab 48

Adsorption

Some substances (cytokines, antibiotics) may adhere directly to the dialyzer

membrane
This process is limited by the binding capacity of the membrane

Modern criteria for the initiation of RRT in the ICU

Oliguria (urine output <200mL/12h)

Anuria (urine output 050mL/12h)
Urea >35mmol/L (98mg/dL)
Creatinine >400mol/L (4.4mg/dL)
K+ >6.5mmol/L or rapidly rising
Pulmonary oedema unresponsive to diuretics
Uncompensated metabolic acidosis (pH <7.1)
Na+ <110 and >160mmol/L
Temperature >40C
Uraemic complications (encephalopathy/myopathy/neuropathy/pericarditis)
Overdose with a dialyzable toxin (e.g. lithium)

If one criterion is present, RRT should be considered.

If two criteria are simultaneously present, RRT is strongly recommended.

Types of RRT

Intermittent hemodialysis (IHD)

The preferred method of RRT in hemodynamically stable patients

Typically performed thrice weekly, but done more often if indicated
Treatment duration is usually 3-4h, extended dialysis may be necessary for toxic
ingestion (e.g., methanol)
Yields high solute clearance through diffusion and rapid fluid removal through
convection

Dr. Ali Ragab 49

Continuous renal replacement therapy (CRRT)

Preferred for patients with significant hemodynamic instability, severe volume

overload, and/or high obligatory daily fluid requirements.
Hourly clearance is lower than IHD, but total daily solute and fluid removal
typically greater

Slow continuous ultrafiltration (SCUF)

Ultrafiltrate is removed slowly, but not replaced

Used for fluid removal with minimal solute clearance

Continuous venovenous hemofiltration (CVVH)

Large volumes of ultrafilrate (>1.5L/h) removed via convection and replaced

with a physiologic crysralloid (replacement fluid)

Continuous venovenous hemodiafiltration (CVVHD)

Combination of CVVH and IHD.

Slow low efficiency dialysis (SLED)

Similar to IHD, but with much slower blood and dialysate flows conducted over
a longer duration.

Peritoneal dialysis (PD)

Used principally for ESRD and rarely for AKI because of difficulty in placing PD
catheter and for potential impairment of pulmonary mechanics
Recent abdominal surgery is a relative contraindication

Dr. Ali Ragab 50

Access

Vascular access

Temporary

Dual lumen venous catheter

Tunneled

Preferred when the expected duration of RRT >3wk

Most commonly placed in right internal jugular vein

Non tunneled

Preferred for expected short duration.

Access sites include internal jugular, subclavian (higher risk of central venous
stenosis), or femoral veins (associated with increased infection rate when
catheter is in place for >5d)

Permanent

Arteriovenous fistula (AVF)

Preferred access for patients with ESRD

Surgical anastomosis of an artery and vein increases venous flow and causes
enlargement (maturation) of the fistula over weeks to months
Not useful for AKI (prolonged maturation) or CRRT (risk of AVF rupture with
prolonged needle cannulation)

Arteriovenous graft (AVG)

Surgical placement of large caliber synthetic conduit connecting an artery and

vein
It can be used within 2-3 wks
Not useful for AKI or CRRT

Dr. Ali Ragab 51

PD catheters

Temporary

Rarely used due to risks of catheter placement and infection

Permanent

Soft, Dacron cuffed catheters placed surgically

Typically require 2wk to mature
Early use has high incidence of leakage from the catheter site.

Anticoagulation

To prevent clotting of the extracorporeal system during RRT, avoid in patient with
active or at high risk for hemorrhage

Heparin

Typically used with IHD

Can be used for CRRT, but may have higher rates of filter thrombosis and
bleeding complications than citrate
Contraindicated in heparin induced thrombocytopenia (HIT)

Citrate

Used extensively with CRRT

Regional anticoagulation achieved by calcium chelation and arrest of the
coagulation cascade
This effect reversed by postdialyzer calcium infusion
Caution in liver disease

Prostacyclin

A short acting agent that blocks platelet aggregation through arachidonic

metabolite inhibition
Use limited due to hypotensive effect and cost

Dr. Ali Ragab 52

RRT fluids

Dialysate solutions

The chemical composition closely resembles normal plasma, but does not
contain metabolic waste products such as urea or creatinine
Dialysate sodium concentration can be varied between 130-170mEq/L to
minimize hypotension secondary to intracellular water shifts from acute
reductions in plasma osmolality
Dialysate potassium concentration is set based on plasma potassium level,
lower concentrations (1-2mEq/L) remove more potassium, while higher
concentrations (3-4mEq/L) may replete potassium
Bicarbonate concentration is typically 30-35mEq/L to replete buffer

Peritoneal dialysate

Contain various dextrose concentrations (1 .5%, 2.5%, and 4.25%) to generate

the osmotic gradient for diffusion of fluid.
Higher concentrations increase solute and fluid removal
Monitor serum glucose levels in diabetics

Complications of IHD

Hypotension

Common complication that can occur without volume removal due to water
shifts induced by solute clearance.
Can be partially prevented by cooling of dialysate (promotes vasoconstriction
and improved myocardial contractility) and careful control of volume removal

Dysequilibrium syndrome

Neurologic symptoms, most commonly dizziness and headache, caused by

transcerebral fluid shifts after dialysis.
Can be avoided by limiting solute clearance during initial dialysis sessions

Dr. Ali Ragab 53

Hypoxemia

Due to alveolar hypoventilation and intrapulmonary leukostasis from cytokine

release and complement activation triggered by reaction to dialyzer membrane.
Clinically significant only in patients with severe cardiopulmonary disease.

Infection

Due to either dialysis catheter or needle cannulation site infection or break in

sterile technique.

Technical errors

Air embolism and blood leaks (rare with adequate precautions)

Hemorrhage

Mandates a cautious use of anticoagulation.

Complications of CRRT

Same as HD, except no dysequilibrium syndrome.

Hypocalcemia

Citrate is hepatically metabolized to bicarbonate and can accumulate in liver

failure causing dramatic drop in ionized calcium despite normal or high total
serum calcium due to chelation by citrate.
Monitor both ionized and total calcium level regularly

Hypophosphatemia

Phosphate clearance high with CRRT

Intravenous phosphate replacement usually required

Metabolic alkalosis

Dr. Ali Ragab 54

Complications of peritoneal dialysis

Infection

Peritonitis from introduction of pathogens into the dialysis system during

dialysate exchanges.
Begin empiric therapy with vancomycin and ceftazidime pending culture results
if suspected.
Staphylococcus aureus and Staphylococcus epidermidis most commonly
isolated, Gram-negative bacteria and fungi are occasionally culpable

Glomerulonephritis (GN)

Definition

Glomerulonephritis simply means inammation of the glomeruli and nephrons

Presentation

Many patients present with specic syndromes

Syndrome GFR Urine BP

Nephrotic Normalmild Proteinuria >3.5g/d Normalmild
Nephritic Moderatesevere Haematuria (mildmacro) Moderatesevere

Dr. Ali Ragab 55

Causes

Generally considered primary (no underlying drive to disease) or secondary

(infection, autoimmunity or malignancy)

Syndrome Common primary causes Common secondary causes

Nephrotic 1. Membranous 1. Diabetes
2. Minimal change 2. SLE (class V nephritis)
3. FSGS 3. Amyloid
4. Mesangiocapillary GN 4. Hepatitis B/C
Nephritic 1. IgA nephropathy 1. Post streptococcal
2. Mesangiocapillary GN 2. Vasculitis
3. SLE (other classes of nephritis)
4. Anti-GBM disease
5. Cryoglobulinaemia

General investigations

Blood

FBC, U&E, LFT, ESR, CRP

Immunoglobulins, electrophoresis
Complement (C3, C4)
Autoantibodies ANA, ANCA, anti-dsDNA, anti-GBM
Blood culture
ASOT, HBsAg, anti-HCV

Urine

RBC casts, MC&S, Bence Jones protein, ACR

Imaging

CXR, renal ultrasound

Dr. Ali Ragab 56

Renal biopsy

What is affected (mesangial cells, capillaries, basement membrane,

endothelium)
How much of the kidney is involved (focal vs diffuse)
How much of the glomerulus is involved (segemental vs global)
What is seen on immunouorescence (deposition of Igs, complement, immune
complexes or pauci immune) and electron microscopy

General management

Early referral to a nephrologist

Keep BP <130/80, or <125/75 if proteinuria >1g/d
Include an ACE-i or ARBs as these have proven benets in reducing proteinuria
and preserving renal function; however, there is no additional benet from dual
therapy

Specic types of glomerulonephritis

IgA nephropathy

Commonest GN in the developed world

Most present with macro- or microscopic haematuria; occasionally
nephritic syndrome

Typical patient

Young man with episodic macroscopic haematuria, recovery is often rapid

between attacks

There is IgA, possibly due to infection, which forms immune complexes and
deposits in mesangial cells

Renal biopsy

Mesangial proliferation

Dr. Ali Ragab 57

Immunouorescence (IF)

Shows deposits of IgA and C3

Treatment

BP control with ACE-i

With nephritic presentation immunosuppression may slow decline of renal
function

Prognosis

Worse if BP, male, proteinuria or renal failure at presentation

20% of adults develop ESRF over 20yrs

Henoch Schnlein purpura (HSP)

HSP is a systemic variant of IgA nephropathy, causing a small vessel vasculitis

Features

Purpuric rash on extensor surfaces (typically on the legs)

Flitting polyarthritis
Abdominal pain (GI bleeding)
Nephritis

Diagnosis

Usually clinical
Conrmed with positive IF for IgA and C3 in skin or renal biopsy (identical to
IgA nephropathy)

Treatment

Same as IgA nephropathy

Dr. Ali Ragab 58

Prognosis

15% nephritic patients ESRF

If both nephritic and nephrotic syndrome, 50% ESRF

Systemic lupus erythematous (SLE)

of patients with SLE will have evidence of renal disease with vascular,
glomerular, and tubulointerstitial damage
Split into class IIV (increasing severity) and class V (membranous)
Requires early treatment

Anti glomerular basement membrane (GBM) disease

Also known as Goodpastures disease

Immunology

Caused by auto-antibodies to type IV collagen (an essential component of

the GBM)
Type IV collagen is also found in the lung and pulmonary haemorrhage can
occur, especially in smokers

Presentation

Present with haematuria/nephritic syndrome

AKI may occur within days of onset of symptoms

Treatment

If treatment (plasma exchange, steroids cytotoxics) is started early, full recovery

is possible and relapses are rare

Renal prognosis

Poor if dialysis-dependent at presentation

Dr. Ali Ragab 59

Post-streptococcal GN

A diffuse proliferative GN occurs 112 weeks after a sore throat or skin infection

Immunology

A streptococcal antigen is deposited on the glomerulus, causing a host

reaction and immune complex formation

Presentation

Usually nephritic syndrome

Investigations

Renal biopsy

Not usually done unless atypical presentation

Inammatory reaction affecting mesangial and endothelial cells

Immunouorescence

IgG and C3 deposits

Serology

ASOT; C3

Treatment

Supportive >95% recover renal function

Rapidly progressive GN (RPGN)

The most aggressive GN, with potential to cause ESRF over days

Dr. Ali Ragab 60

RPGN is classied pathologically into 3 categories

Immune complex disease (45% of cases) eg post infectious, SLE, IgA/HSP

Pauci-immune disease (50% of cases, 8090% ANCA +ve)

Granulomatosis with polyangiitis (C-ANCA +ve)

Microscopic polyangiitis (P-ANCA +ve)
Churg Strauss syndrome

Anti-GBM disease (3%) Goodpastures disease

Clinically

AKI systemic features (eg fever, myalgia, weight loss, haemoptysis)

Pulmonary haemorrhage is the commonest cause of death in ANCA +ve
patients

Treatment

Aggressive immunosuppression with high-dose IV steroids and

cyclophosphamide
With or without plasma exchange

Prognosis

5-year survival 80%

The nephrotic syndrome

If there is oedema, dipstick MSU for protein to avoid missing renal disease.

Denition

The nephrotic syndrome is a triad of

Proteinuria >3.5g/24h (ACR >250mg/mmol)

Hypoalbuminaemia (<25g/L, usually much lower)
Oedema

Dr. Ali Ragab 61

Severe hyperlipidaemia (total cholesterol >10mmol/L)(>386mg/dL) is often present

Causes

Nephrotic syndrome is not a diagnosis; therefore the underlying cause should always
be sought. It can be due to primary renal disease or secondary to a number of
systemic disorders

Primary causes

Minimal change disease

Membranous nephropathy
Focal segmental glomerulosclerosis (FSGS)
Mesangiocapillary GN (MCGN)

Secondary causes

Hepatitis B/C (usually membranous, hep C can cause MCGN)

SLE (class V lupus nephritis causes a membranous pattern)
Diabetic nephropathy
Amyloidosis
Paraneoplastic (usually membranous pattern)
Drug related (again usually membranousNSAIDS, penicillamine, anti-TNF,
gold)

Pathophysiology

Injury to the podocyte appears to be the main cause of proteinuria, podocytes

wrap around the glomerular capillaries and maintain the ltration barrier,
preventing large molecular weight proteins from entering the urine.
Effacement of the foot processes or loss of podocytes can cause heavy protein
loss

Dr. Ali Ragab 62

Assessment

Presentation

Patients present with pitting oedema, which can be severe and rapid onset,
occurring in dependent areas and areas of low tissue resistance, eg periorbitally

History

Ask about acute or chronic infections, drugs, allergies, systemic symptoms

suggestive of autoimmunity or malignancy.

Signs

Urine dip shows ++++ protein, albumin is low, BP is usually normal or mildly
increased, renal function is usually normal or mildly impaired

Differential diagnosis

CCF (JVP, pulmonary oedema, mild proteinuria)

Liver disease

In children

Minimal change GN is the commonest cause of nephrotic syndrome and a

trial of steroids causes resolution in 90%.
Biopsy is avoided in children unless no response to steroids or if clinical
features suggest another cause, eg age <1yr, family history, extrarenal
disease (eg arthritis, rash, anaemia), renal failure, haematuria

In adults

All adults should undergo a biopsy as well as full assessment

Renal biopsy is more difficult in patients with nephrotic syndrome because of
gross oedema and a hypercoagulable state

Dr. Ali Ragab 63

Complications

Susceptibility to infection

(eg cellulitis, Streptococcus infections and spontaneous bacterial peritonitis)

happens in up to 20% of adult patients because of serum IgG, complement
activity, and T cell function (due to loss of immunoglobulin in urine and
also to immunosuppressive treatments)

Thromboembolism

Up to 40%, eg DVT/PE, renal vein thrombosis.

This hypercoagulable state is partly due to clotting factors and platelet
abnormalities.

Hyperlipidaemia

Cholesterol and triglycerides, thought to be due to hepatic lipoprotein

synthesis in response to low oncotic pressure

Treatment

Reduce oedema

Loop diuretics, eg furosemide are used, often high doses are needed
Gut oedema may prevent oral absorption so IV route is useful
Check daily weight (aim for 0.51kg loss/d) and daily U&Es.
Fluid restrict to 1L/day and salt restrict while giving diuretics

Reduce proteinuria

ACE-i or ARB should be started in all patients

Dr. Ali Ragab 64

Reduce risk of complications

Anticoagulate if nephrotic range proteinuria

Start a statin to reduce cholesterol (although often resolves spontaneously
when cause treated)
Treat infections promptly and vaccinate (pneumovax II, u)

Treat underlying cause

Find and treat underlying infections, malignancy or systemic disease

Stop causative drugs

Histological patterns of nephrotic syndrome

Minimal change

Commonest cause of nephrotic syndrome in children (76%, and 20% of

nephrotic adults)
In adults it can be idiopathic or in association with drugs (NSAIDS) or
paraneoplastic (usually Hodgkins lymphoma)

Biopsy

Normal under light microscopy (hence the name).

Electron microscopy shows effacement of the podocyte foot processes

Treatment

90% of children and 70% of adults undergo remission with steroids, but the
majority relapse
Frequently relapsing or steroid-dependent disease is treated with
cyclophosphamide or ciclosporin/tacrolimus.

Prognosis

1% ESRF.

Dr. Ali Ragab 65

Membranous nephropathy

Accounts for 2030% of nephrotic syndrome in adults; 25% in children

Etiology

Mostly idiopathic, but can be associated with malignancy, hepatitis B, drugs

(gold, penicillamine, NSAIDS) and autoimmunity (thyroid, SLE)

Investigations

Biopsy

Diffusely thickened GBM

Immunouorescence (IF)

IgG and C3 subepithelial deposits

Treatment

Secondary involves treating the underlying cause, proteinuria often remits

with, eg control of hepatitis B viraemia
In idiopathic membranous, treatment involves general measures such as
ACE/ARB and diuretics
However, with the discovery that antibodies directed against the
phospholipase A2 receptor are found in up to 80% of patients with idiopathic
membranous nephropathy, interest is growing in immunosuppressive
therapy
Trials are ongoing into the use of the modied Ponticelli regimen
(alternating IV steroids with chlorambucil/cyclophosphamide)
In patients who are anti-PLA2 antibody positive rituximab is also being
trialled.

Dr. Ali Ragab 66

Mesangiocapillary GN

Divided into immune complex (IC) mediated and complement mediated.

IC mediated

IC mediated is driven by circulating immune complexes, which deposit in

the kidney and activate complement via the classical pathway
An underlying cause can be found in most cases, eg hepatitis C, SLE and
monoclonal gammopathies.

Complement mediated

Complement mediated is less common and involves persistent activation of

the alternative complement pathway, eg C3 nephritic factor.
Patients can have extra-renal manifestations, eg Drusen in the retina

Investigations

Biopsy

Mesangial and endocapillary proliferation, a thickened capillary basement

membrane, double contouring (tramline) of the capillary walls.

Immunouorescence

Immunouorescence can show Ig staining, complement staining or light

chains depending on cause.

Electron microscopy

Electron microscopy shows electron dense deposits

Dr. Ali Ragab 67

Treatment

Treatment of the underlying cause as priority

ACE/ARB for all
Immunosuppression if rapid progression of disease with steroids
cyclophosphamide if rapid deterioration in renal function
Given the role of complement, it is possible that new complement targeted
therapies such as eculizumab may be trialled

Prognosis

Poor where no underlying cause can be found

In patients who reach ESRF (usually idiopathic disease) it can recur in
transplants and lead to graft loss

Focal segmental glomerulosclerosis (FSGS)

Etiology

May be primary (idiopathic) or secondary (vesicoureteric reux, IgA

nephropathy, Alports syndrome, vasculitis, sickle-cell disease, heroin
use).
HIV is associated with the collapsing subtype (poor prognosis).

Presentation

Usually nephrotic syndrome or proteinuria

50% have impaired renal function

Investigations

Biopsy

Some glomeruli have scarring of certain segments (ie focal sclerosis)

Immunouorescence

IgM and C3 deposits in affected areas.

Dr. Ali Ragab 68

Treatment

Responds to corticosteroids in 30%

Cyclophosphamide or ciclosporin are considered if steroid-resistant

Prognosis

Untreated most progress to ESRF

Spontaenous remission probably <10%
Those presenting with abnormal renal function have much poorer prognosis,
3050% ESRF.
It recurs in approx. 20% of transplanted kidneys, and may respond to plasma
exchange.

Diuretics

Loop diuretics

Drugs

eg furosemide, bumetanide

Mechanism

Block the Na+/K+/2Cl- co transporter in the thick ascending limb of the

loop of Henle, hence increase the solute load of the ltrate and reduce
water resorption

Effects

Signicant loss of water and Na+, Cl-

Ca2+, K+ and H+ excretion is also increased

Dr. Ali Ragab 69

Clinical use

They are absorbed from the GI tract, and given orally they act within 1 hour
IV the peak effect is seen within 30 minutes so they are useful in treating acute
pulmonary oedema
Widely used in peripheral oedema (heart failure, ascites)
They can also be used to treat severe hypercalcaemia

Side effects

Hypokalaemic metabolic alkalosis (because of K+ and H+ excretion)

Hypovolaemia
Ototoxicity
Allergic reactions

Thiazide diuretics

Drugs

eg bendroumethiazide, indapamide, metolazone

Mechanism

They inhibit the Na+ Cl- transporter in the distal convoluted tubule
They decrease Na+ Cl- resorption and hence increase water loss

Effects

Moderate Na+ and Cl- excretion

They result in low urine Ca2+ by increasing urinary Ca2+ resorption (the
opposite effect of loop diuretics)
They can cause profound hypokalaemia due to excessive K+ loss
Excretion of uric acid is reduced, and Mg2+ is increased

Dr. Ali Ragab 70

Use

Their action begins within 12 hours after ingestion, and lasts for 1224 hours
Useful in BP, long-term treatment of oedema (eg heart failure)
They can reduce renal stone formation in patients with idiopathic
hypercalciuria by decreasing urine calcium concentrations

Side effects

Hypokalaemia
Hyponatraemia
Hypomagnesaemia
Metabolic alkalosis
Hyperglycaemia
Increased serum lipid and uric acid levels (thiazide diuretics are
contraindicated in gout)

Potassium-sparing diuretics

Mechanism

Spironolactone and eplerenone are aldosterone antagonists and hence

inhibit the sodium retaining action of aldosterone
Amiloride and triamterene block sodium channels in collecting tubules
Both types decrease K+ excretion

Effects

They increase Na+ excretion and decrease K+ and H+ excretion

There is a mild associated diuresis
The onset of action of spironolactone is very slow, and takes several days to
have its full effect
Amiloride has a much faster onset and duration of action of only 1216 hours

Dr. Ali Ragab 71

Use

Usually used to control the K+ wasting caused by loop diuretics or

thiazides and are given as combination therapy
Spironolactone and eplerenone have signicant benets in
hyperaldosteronism

Side effects

Hyperkalaemia is common
Metabolic acidosis can occur
Anti androgenic effects (eg gynaecomastia) are seen with spironolactone
GI upset

Osmotic diuretics

Mechanism

Mannitol is a solute that is freely ltered at the glomerulus but poorly

reabsorbed from the tubule, so it remains in the lumen and holds water by
osmotic effect
The reduction in water reabsorption occurs in the proximal tubule and loop of
Henle and also slightly increases Na+ loss

Effects

Mannitol can reduce brain volume and intracranial pressure by osmotically

extracting water from the tissue into the blood

Use

Haemolysis
Rhabdomyolysis
Reducing intra ocular and intra cranial pressures

Dr. Ali Ragab 72

Side-effects

Na+, headache, nausea, vomiting

In patients who are unable to form urine the transient expansion of the
extracellular uid when water is extracted from intra-cellular uid can cause
pulmonary oedema

Carbonic anhydrase inhibitors

Drugs

Such as acetazolamide

Effects

Act on the proximal tubule to increase excretion of bicarbonate and

consequently sodium, potassium and water
This causes alkalinization of the urine and hence a mild metabolic acidosis

Uses

They are not used as diuretics but are still available for use in glaucoma to
reduce the formation of aqueous humour
It is also used by climbers (as Diamox) to increase respiration (the bodys
attempt is to clear the acidosis) and hence improve acclimatization to altitude
and reduce the risk of acute mountain sickness (with its rare but deadly
complications of high altitude pulmonary and cerebral oedema)

Dr. Ali Ragab 73

 Interstitial nephritides and nephrotoxins

Acute interstitial nephritis (AIN)

Definition

AIN is characterised by acute inflammation affecting the

tubulointerstitium of the kidney

Mediated by

Mediated by an immune reaction to drugs, infections or autoimmune disorders

Drugs (NSAIDS, antibiotics, diuretics, allopurinol, omeprazole, phenytoin)

Infections (Staphs, Streps, Brucella, Leptospira, several viruses)
Immune disorders (eg SLE, sarcoidor no obvious cause)

Take a full drug history including over-the-counter and herbal preparations

Features

Usually mild renal impairment (raised BP/oliguria) (indicate worse

prognosis)
Drug reactions (allergic picture with fever, rash and peripheral eosinophilia)

Biopsy

Biopsy shows (inammatory cell inltrate in the interstitium)

Treatment

Stop/treat causative agent

If renal function does not improve within a week then trial of prednisolone
1mg/kg/24h for 4 weeks may improve

Prognosis

Generally good if caught early

Dr. Ali Ragab 74

Chronic tubulointerstitial nephritis (CIN)

Definition

CIN is characterised by renal dysfunction with fibrosis and infiltration of

the renal parenchyma by lymphocytes, plasma cells and macrophages, in
association with tubular damage

Etiology

All causes of ATN if persistent

Diseases

Diabetes mellitus, Sickle cell disease or trait, SLE/vasculitis, Sarcoidosis,

Myeloma

Metabolic

Hyperuricaemia, Nephrocalcinosis, Hyperoxaluria

Miscellaneous

Hypertension, Balkan nephropathy, Herbal nephropathy, Alports syndrome

Clinical features

Presentation

Most patients with CIN present in adult life with CKD, hypertension and
small kidneys

The CKD is often moderate (stage 3) but, because of tubular dysfunction,

electrolyte abnormalities are typically more severe, resulting in hyperkalaemia
and acidosis

Dr. Ali Ragab 75

Management

Management is supportive in nature

Correction of acidosis and hyperkalaemia
Replacement of fluid and electrolytes, as required
RRT if irreversible renal damage has occurred

Analgesic nephropathy

History

History is of chronic, heavy analgesic use, usually NSAIDs, commoner in

women

Complain

Patients may complain of loin pain (papillary necrosis) but it is often silent
until late CKD

Investigations

Urinalysis

Sterile pyuria and mild proteinuria but may be normal

USS

Shows small and irregular kidneys

IVU

IVU shows the classic cup and spill appearance but CT without contrast is
more sensitive

Biopsy

Biopsy shows CIN

Dr. Ali Ragab 76

Treatment

Stop/treat cause

Sudden ank pain should prompt an ultrasound or CT urogram to look for

obstruction from a sloughed papilla

There is risk of atherosclerosis in these patients

Aristolochic acid

Aristolochic acid is a nephrotoxin found in plants endemic to areas along the River
Danube (Balkan herb nephropathy) and some Chinese medicine (Chinese herb
nephropathy)

It can cause CIN in genetically susceptible individuals

Clinical features

There is a long duration between exposure and disease presentation

Patients are usually normotensive, BP only develops with ESRF
There is risk of urothelial tumours

Urate nephropathy

Acute crystal nephropathy

Definition

AKI due to uric acid precipitation within the tubules

Etiology

It is most often due to tumour lysis syndrome, seen in haematological

malignancies after chemotherapy which leads to overproduction of uric acid

Dr. Ali Ragab 77

Investigations

The renal parenchyma appears bright on USS

Plasma urate is often markedly raised
Urinary birefringent crystals on microscopy

Management

Keep well hydrated

Allopurinol pre-chemo
Urinary alkalinization with sodium bicarbonate (solubility of uric acid)

Chronic urate nephropathy

Much reduced incidence with improved diet and earlier treatment of gout
with allopurinol
Hyperuricaemic nephropathy is associated with several familial disorders
including familial juvenile gout and xanthinuria

Hypercalcaemia

Can cause AKI whatever the cause (myeloma, sarcoid, malignancy,

nephrocalcinosis, etc)
Reduce the calcium acutely with rehydration and IV bisphosphonates but
ultimately treat the underlying cause

Radiation nephritis

Definition

Radiation nephritis is renal impairment following radiotherapy and occurs

acutely (<1 year) or can have a chronic onset (years later)

Signs

BP, proteinuria, progression to ESRF

Dr. Ali Ragab 78

Biopsy

Biopsy shows interstitial brosis

Management

Strict BP control

Prevention

During radiotherapy, ensure adequate shielding (or exclusion) of renal areas

Nephrotoxins

Many agents may be toxic to the kidneys and cause acute kidney injury (AKI), usually
by direct acute tubular necrosis, or by causing interstitial nephritis

Analgesics (NSAIDS)
Antimicrobials (gentamicin, sulfonamides, penicillins, rifampicin,
amphotericin, acyclovir)
Anticonvulsants (lamotrigine, valproate, phenytoin)
Other drugs (omeprazole, furosemide, thiazides, ACE-i and ARBS,
cimetidine, lithium, iron, calcineurin inhibitors, cisplatin)
Anaesthetic agents (methoxyurane, enurane)
Radiocontrast material
Crystals (urate)
Toxins (aristolochia, cadmium, lead, arsenic, ethylene glycol)
Haemoglobin (haemolysis, myoglobin in rhabdomyolysis)
Proteins (Igs in myeloma, light chain disease)
Bacteria (streptococci, legionella, brucella, mycoplasma, chlamydia, TB,
salmonella, campylobacter)
Viruses (EBV, CMV, HIV, polyoma virus, adenovirus, measles)
Other (leptospirosis, syphilis, toxoplasma, leishmania)

Dr. Ali Ragab 79

Aminoglycosides

Drugs

(gentamicin, amikacin, streptomycin) are well-recognized nephrotoxins

Presentation

Typically give mild non-oliguric AKI, 12wks into therapy

Risk

Risk is by

Old age, renal hypoperfusion, pre-existing CKD, high dosage/prolonged

treatment, and co-administration of other nephrotoxins

Recovery may be delayed or incomplete

Single bolus doses of aminoglycosides can be as effective as multiple doses in treating

infection and less nephrotoxic

Radiocontrast nephropathy

Radiocontrast nephropathy is a very common cause of iatrogenic AKI with IV

contrast radiological studies

Risk factors

Risk factors are diabetes mellitus, high doses of contrast medium,

hypovolaemia, other nephrotoxic agents, and previous CKD

Prevention

Stop nephrotoxic agents peri-procedure

Pre-hydrate with IV 0.9% sodium chloride in patients with risk factors
Inform radiology, who may use less nephrotoxic contrast

Dr. Ali Ragab 80

Rhabdomyolysis

Results from skeletal muscle breakdown, with release of its contents into the
circulation, including myoglobin, K+, PO43, urate and creatine kinase (CK)

Complications

Complications include K+ and AKI

Myoglobin is ltered by the glomeruli and precipitates, obstructing renal
tubules

Causes

Post ischaemia

Embolism, clamp on artery during surgery, trauma

Drugs and toxins

Statins, alcohol, ecstasy, heroin, snake bite, carbon monoxide

Infections

Coxsackie, EBV, inuenza

Metabolic

K+, PO43, myositis, malignant hyperpyrexia

Inherited muscle disorders

McArdles disease, Duchennes muscular dystrophy

Others

Prolonged immobilization (eg after falling), burns, crush injury, excessive

exercise, uncontrolled seizures, neuroleptic malignant syndrome

Dr. Ali Ragab 81

Clinical features

Often of the cause, with muscle pain, swelling, tenderness, and red brown
urine

Tests

Plasma CK >1000iU/L (often >10,000iU/L)

MI must be excluded as a cause (troponin negative)
Visible myoglobinuria (tea- or cola-coloured urine) occurs when urinary
myoglobin exceeds 250g/mL (normal <5ng/mL)
Urine is +ve for blood on dipstick but without RBC on microscopy

Others

K+, PO43, Ca2+ (enters muscle), urate

AKI occurs 1224 hours later, and DIC is associated
Compartment syndrome can result from muscle injury

Treatment

Urgent treatment for hyperkalaemia

Hydration

IV uid rehydration is a priority to prevent AKI (maintain urine output at

300mL/h until myoglobinuria has ceased)
Initially up to 1.5L uid/h may be needed
If oliguric, CVP monitoring is useful to prevent uid overload

Sodium bicarbonate

IV sodium bicarbonate is used to alkalinize urine to pH >6.5, to stabilize a

less toxic form of myoglobin.

Dr. Ali Ragab 82

Dialysis

Dialysis may be needed

Prognosis

Good if treated early.

Renovascular disease

Definition

Dened as stenosis of the renal artery or one of its branches

Causes

Atherosclerosis (in 80% >50yrs, arteriopaths often co-existent IHD, stroke or

peripheral vascular disease)
Fibromuscular dysplasia (10%, younger females)
Rarer Takayasus arteritis, antiphospholipid syndrome, post-renal
transplant, thromboembolism, external compression

Signs

BP resistant to treatment
Worsening renal function after ACE-i/ARB in bilateral renal artery stenosis
Flash pulmonary oedema (sudden onset, without LV impairment on cardiac
echo)
Abdominal carotid or femoral bruits, and weak leg pulses may be found

Tests

Renal size asymmetry (affected side is smaller) on USS

Disturbance in renal blood ow on Doppler US
CT/MR angiography are more sensitive
Renal angiography is gold standard but do after CT/MR as it is invasive

Dr. Ali Ragab 83

Treatment

Comprehensive antihypertensive regimens

Transluminal angioplasty stent placement or revascularization surgery
Best medical management is probably superior to revascularization in
atherosclerotic disease

Haemolytic uraemic syndrome (HUS)

HUS is characterized by

Microangiopathic haemolytic anaemia (MAHA) intravascular

haemolysis + red cell fragmentation.
Endothelial damage triggers thrombosis, platelet consumption and fibrin
strand deposition, mainly in renal microvasculature.
The strands cause mechanical destruction of passing RBCs
Thrombocytopenia and AKI result

Causes

90% are from E. coli strain O157

This produces a verotoxin that attacks endothelial cells
This typically affects young children in outbreaks (more common than
sporadically) after eating undercooked contaminated meat

Signs

Abdominal pain, bloody diarrhoea, and AKI

Tests

Urinalysis Haematuria/proteinuria
Blood film Fragmented RBC (schistocytes)
FBC platelets, Hb
Clotting tests are normal

Dr. Ali Ragab 84

Treatment

Seek expert advice

Dialysis for AKI may be needed
Plasma exchange is used in severe persistent disease

Prognosis

Worse in non-E. coli cases

Mortality 35%, good prognosis if caught early

Thrombotic thrombocytopenic purpura (TTP)

There is an overlap between TTP and HUS, and many physicians consider
them a spectrum of disease

Features of TTP

All patients have MAHA (severe, often with jaundice) and low platelets
Other features can include AKI, uctuating CNS signs (eg seizures,
hemiparesis, consciousness, vision) and fever
The classic description included the full pentad of features, but with the
advent of plasma exchange this is rarely seen
Mortality is higher than childhood HUS and can be >90% if untreated, though
reduced to 20% with plasma exchange

Pathophysiology

There is a genetic or acquired deciency of a protease (ADAMTS13) that

normally cleaves multimers of von Willebrand factor (VWF)
Large VWF multimers form, causing platelet aggregation and brin
deposition in small vessels, leading to microthrombi

Dr. Ali Ragab 85

Causes

Idiopathic (40%)
Autoimmunity (eg SLE)
Cancer, pregnancy, drug associated (eg quinine), bloody diarrhoea prodrome
(as childhood HUS), haematopoietic stem cell transplant

It is a haematological emergency

Tests

As HUS
The unexplained occurrence of thrombocytopaenia and anaemia should
prompt immediate consideration of the diagnosis and evaluation of a
peripheral blood smear for evidence of microangiopathic haemolytic
anaemia

Treatment

Urgent plasma exchange may be life saving

Steroids are the mainstay for non-responders
New therapies such as eculizumab (monoclonal antibody targeting terminal
complement pathway C5) have shown promising results in case reports

Diabetes mellitus and the kidney

In type 1 DM nephropathy

Is rare in the rst 5yrs, after 10yrs annual incidence rises to a peak at 15yrs, then
falls again
Those who have not developed nephropathy at 35yrs are unlikely to do so

Dr. Ali Ragab 86

In type 2 DM

Around 10% have nephropathy at diagnosis and up to half will go on to develop

it over the next 20yrs
20% of people with type 2 DM will develop ESRF
Everyone with DM should be screened annually for microalbuminuria

Microalbuminuria

Microalbuminuria (30300mg albumin/24h) gives early warning of

impending renal problems and is also a strong independent risk factor for
cardiovascular disease

Diagnosis

Standard dipsticks do not detect this, so use specialized dipsticks or estimate

using an albumin:creatinine ratio of >2.5 in men or >3.5 in women

ACE-i and ARBs

Those who are positive should be started on an ACE-i or angiotensin-2 receptor

blockers (ARB), irrespective of blood pressure as these reduce intra-
glomerular pressure and hence proteinuria
Usually, ACE-i are rst-line and ARBS for ACE-i-intolerant individuals
There is currently insufficient evidence that ACE-i and ARB are of additive
benet, in one study, the combination of telmisartan and ramipril was
associated with more adverse events without an increase in benet

Side effects

U&E (monitor K+ and creatinine periodically; stop if there is a rise in creatinine

of >20%), cough (with ACE-i)

Dr. Ali Ragab 87

Target BP

Target BP in DM if no proteinuria (130/80)

If microalbuminuria/proteinuria is present, aim 125/75mmHg

Is microalbuminuria reversible?

If caught early and managed vigorously

Tight glycaemic control

Tight BP control with ACE/ARB
Manage CV risk stop smoking, reduce cholesterol, consider aspirin

Cholesterol emboli

Cholesterol emboli may be released from atheromatous plaques (often aorta)

which lodge in the distal microcirculation (eg renal vessels, peripheral circulation,
gut) to cause ischaemia

An inammatory response leads to fever, myalgia and eosinophils

Risks

Atheroma, cholesterol, aortic aneurysm, thrombolysis, arterial catheterization,

eg during interventional radiological procedures

Signs

Fever, uncontrolled BP, livedo reticularis, oliguria, AKI, gangrene, GI bleeds

Treatment

Haemodynamic monitoring
Nutritional and metabolic support
Dialysis when indicated
Statins are also tried
Avoid anticoagulants and instrumentation

Dr. Ali Ragab 88

Prognosis

Often progressive and fatal; some regain renal function after dialysis

Renal tubular disease

Renal tubular acidosis (RTA)

Definition

A metabolic acidosis due to impaired acid secretion by the kidney

RTA is characterized by

There is a hyperchloraemic metabolic acidosis + normal anion gap

RTA should be suspected when there is a hyperchloraemic acidosis with a
normal anion gap and no evidence of gastrointestinal disturbance.
The urine pH is inappropriately high (> 5.5) in the presence of systemic
acidosis

There are 4 types, type 3 RTA is a rare combination of types 1 and 2

Type 1 (distal) RTA

Due to an inability to excrete H+ and generate acidic urine in the distal

tubule, even in states of metabolic acidosis

Causes

Inherited disorders
Acquired include SLE, Sjgrens and drug related (amphotericin)

Features

Rickets (+ growth failure) or osteomalacia, due to buffering of H+ with

calcium in bone

Dr. Ali Ragab 89

 Nephrocalcinosis with renal calculi, leading to recurrent UTIs, is due to a
combination of hypercalciuria, urinary citrate (reabsorbed as a buffer for H+)
and alkaline urine: all favour calcium phosphate stone formation

Tests

Urine pH >5.5 despite metabolic acidosis

Treatment

Oral sodium bicarbonate or citrate

Complications

Are mostly from renal calculiESRF may result from nephrocalcinosis

Type 2 (proximal) RTA

It is caused by failure of sodium bicarbonate reabsorption in the proximal

tubule.

Features

The cardinal features are acidosis, hypokalaemia, an inability to lower the

urine pH below 5.5 despite systemic acidosis, and the appearance of
bicarbonate in the urine despite subnormal plasma bicarbonate

Diagnosis

IV sodium bicarbonate load: there is a high fractional excretion of HCO3

(>15%)

Treatment

High doses of bicarbonate (>10mmol/kg/day) are required

Patients often nd this intolerable

Dr. Ali Ragab 90

Type 4 (hyperkalaemic) RTA

RTA is due to hyporeninaemic hypoaldosteronism

Hypoaldosteronism causes hyperkalaemia and acidosis (K+ and H+
excretion)

Causes

Addisons
Diabetic nephropathy
Interstitial nephritis (SLE, chronic obstruction)
Drugs (K+ sparing diuretics, beta blockers, NSAIDS, ciclosporin)

Treatment

Remove any cause.

Fludrocortisone 0.1mg
Furosemide or Calcium Resonium are used to control K+

Fanconi syndrome

Proximal tubular dysfunction leading to loss of amino acids, glucose,

PO43 and HCO3 in urine

Effects

This causes dehydration, metabolic acidosis, osteomalacia/rickets and

electrolyte abnormalities

Dr. Ali Ragab 91

Causes

Congenital

Idiopathic, cysteinosis, Wilsons disease, tyrosinaemia, Lowe syndrome

Acquired

Heavy metal poisoning (lead, mercury, cadmium, platinum, uranium)

Drugs (gentamicin, cisplatin, ifosfamide)
Light chains (myeloma, amyloid)
Sjgrens

Treatment

Remove any cause and replace losses

K+, sodium bicarbonate, PO43 and vitamin D supplements are used

Cystinosis

There is accumulation of cystine in lysosomes due to an autosomal recessive

defect

Cystine deposits cause

Fanconi syndrome
Visual impairment
Myopathy
Hypothyroidism
Progression to ESRF <10yrs

Treatment

As Fanconi syndrome
Oral cysteamine intralysosomal cystine and delays ESRF, but is poorly
tolerated
Renal cystinosis does not recur after transplant; extra-renal disease progresses

Dr. Ali Ragab 92

Hereditary hypokalaemic tubulopathies

Bartters syndrome (clinically similar to loop diuretics)

Inherited mutation in the co-transporter targeted by LOOP diuretics, so a similar

pattern of metabolic abnormalities

Low K+, metabolic alkalosis, hypercalciuria

Treatment

Replace K+
Consider indomethacin, a prostaglandin synthesis inhibitor, which can resolve
abnormalities

Gitelman syndrome (similar to thiazide diuretics)

Inherited mutation in the co-transporter targeted by THIAZIDE diuretics, so a

similar pattern of metabolic abnormalities

Low K+, metabolic alkalosis, hypocalciuria and low Mg2+

Presentation

Usually present with muscle cramps, weakness and low BP

Treatment

Replace Mg2+
May also require K+ supplementation

Dr. Ali Ragab 93

Inherited kidney diseases

Autosomal dominant polycystic kidney disease (APKD)

Prevalence

Prevalence 1:1000. 85% of patients have mutations in PKD1 (chromosome 16)

and reach ESRF by 50s. Remainder have mutation in PKD2 (chromosome 4) and
have a slower course, reaching ESRF by 70s
Can be clinically silent for many years so family screening is important

Signs

Renal enlargement with cysts

Abdominal pain haematuria (haemorrhage into a cyst)
Cyst infection, renal calculi, BP, progressive renal failure

Extrarenal

Liver cysts
Intra-cranial aneurysm SAH
Mitral valve prolapsed
Ovarian cysts
Diverticular disease

Monitor

Monitor U&E

Dr. Ali Ragab 94

Treatment

Increased BP should be treated aggressively, with target levels of

<130/80mmHg (ACE-i are best choices)
Treat infections
Dialysis or transplantation for ESRF
Genetic counseling
Pain may be helped by laparoscopic cyst removal or nephrectomy
Water intake, Na+ intake, and avoiding caffeine may also help

Screening for PKD

USS screening offers good sensitivity and specicity depending on age

Age 1839yrs >3 unilateral or bilateral cysts

4059yrs >2 cysts in each kidney
>60yrs >4 cysts in each kidney

Have good sensitivity and specicity and a positive predictive value close to 100%

Genetic screening for some PKD2 mutations is available in specialist centres.

Screening for SAH

With magnetic resonance angiography may be done in 1st degree relatives

of those with SAH + ADPKD
Some screen with no family history, especially for certain occupations (eg
pilots)

Autosomal recessive polycystic kidney disease

Prevalence

Prevalence 1:40,000, chromosome 6

Dr. Ali Ragab 95

Signs

Variable, many present in infancy with multiple renal cysts and congenital
hepatic fibrosis

Treatment

There is currently no specic therapy

Genetic counselling of family members is important

Medullary cystic disease

Inherited disorder with tubular loss and medullary cyst formation

The juvenile (autosomal recessive) form accounts for 1020% of ESRF in
children
The adult form (autosomal dominant) is rare

Signs

Shrunken kidneys, cysts restricted to the renal medulla

Salt wasting, polyuria, polydipsia, enuresis (urine concentrating ability),
failure to thrive, renal impairment ESRF

Extrarenal

Retinal degeneration, retinitis pigmentosa, skeletal changes, cerebellar ataxia,

liver brosis

Dr. Ali Ragab 96

Alport syndrome

Prevalence

1:5000. 85% of cases are X-linked, due to mutations in the COL4A5 gene, which
encodes the 5 chain of type IV collagen

Signs

Haematuria, proteinuria and progressive renal insufficiency

Patients often exhibit systemic manifestations, eg sensorineural deafness
and ocular defects (eg lenticonus: bulging of lens capsule seen on slit-lamp
examination)

Pathology

Thickened GBM with splitting

Type IV collagen is the antigen in anti-GBM disease (Goodpastures disease),
hence there is a risk of anti-GBM glomerulonephritis post renal transplant

Treatment

None specic, as for CKD

Hyperoxaluria

Etiology

Primary (inherited enzyme defect)

Secondary increased intake (rhubarb, spinach, tea), increased intestinal
resorption

Presentation

Presents with oxalate renal stones and nephrocalcinosis

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Treatment

Fluid intake
Reduce oxalate in diet
Calcium supplements
Liver transplant is curative in primary hyperoxaluria and can be combined with
renal transplant

Cystinuria

Cystinuria not to be confused with cystinosis

Manifests with cysteine renal stones

Treatment

Fluid intake
Urine alkalinization with potassium citrate

Dr. Ali Ragab 98