RENAL

PATHOPHYSIOLOGY
OBJECTIVES:

1. Students should be able to explain the causes of renal

damage and the mechanism of causing renal failure.
2. They should be conversant with the path of the nephron
that is damaged in a disease condition.

3. They should have a good understanding of how the

various mechanism influence the use of drugs.

INTRODUCTION: The Kidney is complex both structurally and

functionally and plays a central role in homeostasis. Thus a wide range
of clinical conditions can result from the many possible varieties of
renal malfunction. The functional unit of the kidney is the nephron
which consist broadly of the glomerulus and tubules. The formal is
responsible for filtration while the latter for reabsorbtion and secretion.
There are about one million functional nephrons in the kidney
representing considerable functional overcapacity and life can continue
quite normally with less than half a kidney. Thus when the kidneys are
diseased, symptoms do not appear until after there has been extensive
and often irreversible damage, making treatment difficult. Damage to
the kidney can be caused by infection, inflammation, autoimmunity,
neoplasia and toxins. Systemic or local circulatory insufficiency can
also seriously compromise renal function. The commonest clinical
syndromes are glomerular inflammation, urinary tract infection and
nephrotoxicity, especially that caused by drugs. The concern in renal
diseases is ultimate renal failure which they progress to.

The loss of renal function has consequences both complex

and serious. One useful distinction, which help predict or explain the
clinical pictures found in different types and stages of renal failure, is
between glomerular and tubular dysfunction. Although both structures
may be damaged, often the trauma is predominantly to one or other,
e.g glomerulonephritis primarily causes glomerular damage whereas
aminoglycoside nephrotoxicity is mainly tubular. Glomerular damage
results in a fall in GFR with retention of those substances usually
cleared by filtration, including water -oliguria, hypervolaemia, uraemia,
hypocalcemia, hyperphosphataemia, hyperuricaemia, hyperkalaemia
and
 acidosis as clinical
features. On the other hand, tubular damage leads to polyuria ( large
volume of dilute urine) of low specific gravity along with electrolytes
and nutrients. The Kidney is the key organ of overall homeostatic
control and Includes:

Functions:

. Excretory Function- Excretion of water and metabolic waste

. Secretory Function- Produce Renin

. Metabolism of Vitamin D- Calcium metabolism

. Degrade Insulin

. Produce Prostaglandin

. Produce Erythropoetin

. Parathyroid Hormone promotes calcium reabsorption

RENAL FAILURE

Renal failure denotes a global loss of renal function. Its usual criterion
is a GFR of less than 15ml/min. Renal failure is not a specific disease; it
is a complex syndrome with many possible causes but fairly uniform
clinical presentation. Renal failure could be acute or chronic.

Definitions.
 Acute renal failure may be defined as a sudden fall in GFR to below
about 15ml/min. It leads to a reversible impairment in kidney function.

Chronic renal failure may be defined as a slow, progressive and

insidious process that leads to an irreversible loss of renal function.

Chronic kidney disease is defined as having some type of kidney abnormality or

"marker" such as protein in the urine, and having decreased kidney function for three
months or longer.

In ARF the impairment of regulatory and excretory functions

predominates but in the CRF there is also an endocrine abnormality.
Again, ARF is secondary to generalized circulatory failure. It develops
rapidly and has a high mortality but is essentially reversible: if the
patients survives there be no permanent sequelae. CRF has an
insidious onset and usually caused by damage to the renal tissue. The
high natural degree of renal reserve and the slow progression of CRF
mean that irreversible damage has usually occurred by the time the
patient reports symptoms. There is then inexorable decline towards
end stage renal disese which is fatal without dialysis or
transplantation(RRT).

Symptoms: Anorexia, Nausea, vomiting, general swelling, fluid

retention delirium, drowsy, lethargy, hard to arose, progressing to
seizures & coma. Sometimes oliguria or anuria.

Laboratory Findings: Fluid and Electrolyte imbalance, Acid/Base

disorders.

Diagnosis: Based on renal function test: Creatinine test, BUN test.

Etiology Of Acute Renal Failure

Renal failure can occur from an acute situation or from chronic

problems.

In acute renal failure, kidney function is lost rapidly and can occur
from a variety of insults to the body. The list of causes is often
categorized based on where the injury has occurred.

Prerenal causes (pre=before + renal=kidney) causes are due to

decreased blood supply to the kidney. Examples of prerenal causes
of renal failure are:
 . hypovolemia (low blood volume) due to blood loss;

 dehydration from loss of body fluid (for example, vomiting,

diarrhea,burns, sweating, fever);

 poor intake of fluids;

 medication, for example, diuretics ("water pills") may cause
excessive water loss; and
 abnormal blood flow to and from the kidney due to obstruction of
the renal artery or vein.
 Shock and hypotension

• Sepsis: The body's immune system is overwhelmed from

infection and causes inflammation and shutdown of the
kidneys. This usually does not occur with urinary tract infections

Renal causes of Renal failure (damage directly to the kidney itself) include:

 Medications: Some medications are toxic to the kidney,

including nonsteroidal anti-inflammatory drugs aminoglycosides
[gentamicin (Garamycin), tobramycin], lithium (Eskalith,
Lithobid), iodine-containing medications such as those injected
for radiology dye studies.

 Rhabdomyolysis: This is a situation in which there is significant

muscle breakdown in the body, and the damaged muscle fibers
clog the filtering system of the kidneys. this can occur because
of trauma, crush injuries, and burns. Some medications used to
treat high cholesterol can cause rhabdomyolysis.
 Multiple myeloma
 Acute glomerulonephritis or inflammation of the glomeruli, the
filtering system of the kidneys. Many diseases can cause this
inflammation including systemic lupus erythematosus,
Wegener's granulomatosis, and Goodpasture syndrome.

Post renal causes of Renal failure (post=after + renal= kidney) are

due to factors that affect outflow of the urine:

 Obstruction of the bladder or the ureters can cause back

pressure because the kidneys continue to produce urine, but the
obstruction acts like a dam, and urine backs up into the kidneys.
When the pressure increases high enough, the kidneys are
damaged and shut down.
  Prostatic hypertrophy or prostate cancer may block the urethra
and prevents the bladder from emptying.
 Tumors in the abdomen that surround and obstruct the ureters.

Kidney stones. Usually, kidney stones affect only one kidney and do
not cause kidney failure. However, if there is only one kidney present,
a kidney stone may cause the lone kidney to fail.
Acute glomerulonephritis.
The parenchymal tissue affected in this disease is the glomeruli. The
glomeruli seem especially sensitive to inflammatory immune damage,
and most forms of glomerular disease involve immunological
mechanism. This is usually the post-streptoccocal form usually seen in
children or young adults. A few weeks after, for example, a throat
infection a very abrupt and severe renal inflammatory response
develops. Disease severity usually correlates with the patient’s titre of
anti-streptolysin antibody (ASA). Other less significant causes includes
malaria, bacteria endocarditis. Drug reactions and connective tissue
disorders are other possible causes. Most cases involves immune
complex(IC) deposition on the GBM. This results in an acute
inflammatory reaction on the surface of the GBM causing damage to it
making it permeable to protein molecules. This informs the use of
immunosuppressant in this condition.

Medications
Drugs apart from acting as hapten (e.g Penicillines) and causing AGN
through the inflammatory process, they equally cause damage through
nephrotoxicity – Acute tubular necrosis and acute interstitial nephritis.
Pyelonephritis. Pyelonephritis is a condition which develops when
infectious microorganisms establish in the urinary tract and migrate
upward into kidney tissue. The incidence is particularly high in
individuals who contaminate the urethra with fecal material containing
E. coli as a result of poor hygiene or are unable to completely void the
bladder for some reason. The urinary retention leads to excess
microbial growth and eventual spread into the kidneys. Acute tubular
Necrosis: Many bacteria, especially certain strains of Escherichia coli,
secrete toxic materials that can be damaging to the host. In humans,
these toxins may exist in circulating blood at levels too low to cause
problems until they are filtered into the nephron across the
glomerulus. Once filtered into the nephron, tubular reabsorption
results in these toxins being concentrated in the nephron, eventually
reaching a concentration high enough to damage nephron tubule cells
(tubular necrosis).

PostRenal ARF
Renal Calyx (Kidney Stone). Kidney stones result from crystalline
materials that occur in urine in concentrations sufficient to cause
aggregate crystals that grow into stones within the renal pelvis. Once
formed, these stones can move into the ureters and lodge causing
intense pain (renal colic) until they are passed naturally or are
removed surgically or disrupted by ultrasound treatments. A common
kidney stone develops from calcium oxylate salts in people with high
calcium and oxalic acid in their diets. Calcium comes primarily from
dairy products and leafy green vegetables, both of which are common
in southern diets. Oxylates come from plant extracts (coffee, tea, and
cola).

*in prerenal, the tubules work and will therefore absorb back some
urea.

Clinical Presentations.
Acute Renal Failure
 The Oliguric Phase: Urine output is reduced to 50 – 400mL/day.
A urine production of less than 50mL/day is define as anuria.
 The diuretic Phase: There is recovery from the oliguric phase.
 The recovery phase the tubule cells slowly regenerate

Table 2 Urinalysis Findings In Acute Renal Failure

Injury Urinalysis

Prerenal Benign or hyaline casts

Renal
Acute Tubular Necrosis Hemegranular or epithelial cell
casts
Acute Interstitial Nephropathy WBCs, WBC casts, eosinophils,
pro
Acute glomerulonephritis RBCs, dysmorphic RBCs, RBC
casts, Proteinuria

Postrenal Benign ± hematuria

Perioperative Renal Injuries WBC = white blood cell; RBC = red
blood cell.

Acute Tubular Necrosis: This is the term given to ARF caused by

destruction of tubular epithelial cells. It describes acute reversible
tubular damage. It can be an important consequence of acute pre-
renal failure (as above) following circulatory insufficiency when it is
termed vasomotor nephropathy(pls note). Drugs causes direct toxic
damage to the nephrons. The presence of increased concentrations of
B2- microglobulins ( which are normally reabsorbed by the proximal
convulated tubule) in the urine is suggestive of direct acute tubular
necrosis.

Etiology: Ischemia and Nephrotoxic agent

Symptoms similar to acute renal failure. Acidosis, hyperkalemia,

hyperphosphatemia, hypocalcemia with oliguria or anuria are major
findings.

PATHOPHYSIOLOGY
. Acute Renal Failure:
Oliguria
Hemodynamically-Mediated ARF.
Volume depletion is a manifestation of abnormality of fluid distribution:
the patient is either relatively (third space fluid loss such as capillary
leak, or vasodilatation) or absolutely (hemorrhage, dehydration)
hypovolemic. The endpoint is the same: the patient initially
compensates (by the extrinsic system discussed below) to restore
circulating volume. If the injury persists or is not corrected then
decompensation occurs: decompensation = shock and tissue
hypoperfusion. Oliguria is a sensitive indicator of volume depletion.
The afferent arterioles that supply the glomerulus and the efferent
arterioles that drain the glomerulus are responsible for maintaining an
intraglomerular pressure that is sufficient for ultrafiltration. Therefore,
glomerular capillary hydrostatic pressure and glomerular filtration are
dependent upon renal perfusion, and the tone of afferent and efferent
arterioles is critical for the regulation of the process. In a patient with
compromised renal blood flow(e.g, caused by Blood loss), glomerular
capillary perfusion would be enhanced by afferent arteriolar
vasodilation or efferent arteriolar vasoconstriction. E2 and I2 which
cause dilatation, and also possibly by nitric oxide, endothelin, atrial
natriuretic factor. PGE2 and PGI2 also augment the level of activity of
rennin-angiotensin system.
 Figure 1.1. Schlondorff DO. Overall scheme of
factors and pathways contributing to the progression of renal
disease.

NOTE: In a stressed kidney( one where renal blood flow has been
compromised), glomerular pressure will be maintained by these
compensatory processes. Any interference with these processes, such
as by drugs that inhibit prostaglandin synthesis or inhibit the
production of angiotensin II, may result in acute renal failure. Such
effects normally would not occur in individuals who do not have
compromised renal blood flow.

Tubular Obstruction Mechanism

Renal injuries are caused by damage and destruction of renal
tubules. This may occur due to a variety of different mechanisms,
ultimately all lead to hypoxia and ischemia. It is thought that the
mechanism behind oliguria is ischemic injury to tubular cells which
subsequently slough off as casts and block the passage of fluid through
the nephron. Pressure builds up in the pre-obstruction area, and is
reflected backwards towards the Bowman’s Capsule. As the pressure
increases, less and less is filtered, and oliguria becomes pathological.
When the pressure in the Capsule equals the net filtration pressure,
filtration stops and the patient becomes anuric. One of the reasons
why some experts recommend the use of diuretics is to flush debris
out of the nephrons, and allow filtration and passage of urine.

Mechanism II
This can be caused by factors that damages renal parenchymal
tissue. The kidney is especially prone to immunological or toxic
damage. This is probably because in its excretory role it concentrates
the products of the immune system, e.g . immune complexes, and of
metabolism and its high blood flow exposes it to potential toxins far
more than most organs. Glomerular and tubulo-interstitial tissues tend
to be affected independently by different aetiological agencies,
although some conditions affect both, e.g ischaemia following
circulatory failure. Intrinsic damage is usually a chronic process but
toxic or ischaemic nephropathy can be acute. In the early stages of
ARF, renal vasoconstriction occurs in the renal cortex, resulting in
ischemia and reduction in GFR, leading to oliguria. The renin-
angiotensin-aldosterone system may contribute to vasoconstriction
and oliguria. Renin is released when plasma volume is low. The
secretion of renin causes convertion of angiotensinogen to angiotensin,
finally leading to vasoconstriction. Thus the afferent arteriole constricts
which leads to decreased GFR and oliguria.

Chronic renal failure

develops over months and years. The most common causes of chronic
renal failure are related to:

 poorly controlled diabetes,

 poorly controlled high blood pressure, and

 chronic glomerulonephritis.

Less common causes of chronic renal failure include:

 polycystic kidney disease,

 reflux nephropathy,
 kidney stones, and
 prostate disease.

The main causes of renal injury are based on immunologic reactions

(initiated by immune complexes or immune cells), tissue hypoxia and
ischaemia, exogenic agents like drugs, endogenous substances like
glucose or paraproteins and others, and genetic defects. Irrespective of
the underlying cause glomerulosclerosis and tubulointerstitial fibrosis
are common to CRD. An overview of the pathophysiology of CRD
should give special consideration to mechanisms of glomerular,
tubular and vascular injury.

Signs and Symptoms

. Elivation of serum creatinine and other metabolic waist
. Proteinuria and Heamaturia
. Hypertension
. Anemia
. Tiredness or Fatigue
. Puffiness or Swelling
. Back Pain
. Itching.
. Loss of Appetite
. Changes in Urination(amount (Oliguria), Colour, Frequency)
. Poor Digestion.

Mechanism of glomerular impairment

Chronic Glomerulonephritis. Glomerulonephritides are a group of
kidney diseases that affect the glomeruli. They fall into two major
categories: glomerulonephritis refers to an inflammation of the
glomeruli and can be primary or secondary, and glomerulosclerosis
refers to scarring of the glomeruli. Even though glomerulonephritis
andglomerulosclerosis have different causes, both can lead to ESRD.
They could be Hereditory or Acquired.
Hereditary defects account for a minority of glomerular disease. A
prototype of an inherited glomerular disease is the Alport’s syndrome
or hereditary nephritis, usually transmitted as an X-linked dominant
trait although autosomal dominant and recessive forms have been
reported as well. Usually transmitted as an X-linked dominant trait
although autosomal dominant and recessive forms have been reported
as well. In its classical X-linked form there is a mutation in the COL4A5
gene that encodes the α5 chain of type IV collagen located on the X
chromosome. As a consequence, GBM is irregular with longitudinal
layering, splitting or thickening, and the patient develops progressive
glomerulosclerosis and renal failure.
Acquired glomerular disease is triggered by immune mediated
injury, metabolic and mechanical stress. In this condition, antibody
complexes resulting from a recent infection collect on the glomerular
membrane on the circulatory side and cause a secondary glomerular
inflammation. This glomerular inflammation can cause permanent
nephron damage by fibrous connective tissue infiltration which
interferes with the glomerular filtration process. Streptococcal
infections are notorious as causative agents of acute
glomerulonephritis. Consequently, something as simple as a “strep
throat” can have serious consequences. From a pathological and
pathogenetic point of view glomerular diseases can broadly be divided
into three groups:
• nonproliferative (without cell proliferation) glomerular diseases
without glomerular inflammation and without deposition of
immunoglobulins (minimal change disease, idiopathic focal, and
segmental glomerulosclerosis [FSGS]) or with deposition of
immunoglobulins, but without glomerular inflammation, most likely
because of subepithelial localization of immunoglobulins (e.g.,
membranous nephropathy)
• proliferative glomerular diseases with deposition of immunoglobulins
leading to increased cellularity (proliferative glomerulonephrites, e.g.,
lupus nephritis, IgA nephropathy, anti-GBM, postinfectious GN), or with
severe glomerular injury and inflammation, but without deposition of
immunoglobulins (e.g., pauci-immune glomerulonephritis).
• heterogenous group of glomerular diseases in systemic diseases like
diabetes, amyloidosis and paraproteinemia. The podocyte seems to
occupy the central role in the pathogenesis of the first group of
glomerular diseases as well as in diabetic nephropathy. In the second
group of glomerular diseases with cell proliferation, either deposition of
immune complexes from the circulation or formed in situ lead to
activation of intrinsic renal cells (via Fc receptors and complement
cascade activation), resulting in inflammatory cell recruitment.
Futhermore, severe glomerular injury and inflammation can occur
without discernible immune complexes in the glomeruli, as in ANCA
(antineutrophil cytoplasmic antibodies) positive glomerulonephritis.
The offending etiologic agents are mainly unknown, with the rare
exception of ß hemolytic streptococci in poststreptococcal
glomerulonephritis, and hepatitis C virus in type 1 cryoglobulinemic
membranoproliferative glomerulonephritis.

Systemic hypertension translated to glomeruli and glomerular

hypertension resulting from local changes in glomerular
hemodynamics may cause glomerular injury. The kidney is normally
protected from systemic hypertension by autoregulation which can be
overwhelmed by high blood pressure, meaning that systemic
hypertension is translated directly to glomerular filtration barrier
causing glomerular injury. Chronic hypertension leads to arteriolar
vasoconstriction and sclerosis with consequent secondary sclerosis and
glomerular and tubulointerstitial atrophy. Because of the large number
of small diameter blood vessels associated with the kidney, kidney
function is extremely sensitive to high blood pressure. Elevated
pressures can cause blood vessel damage as plasma leaks into the
artery wall under pressure. This plasma infiltration begins an
inflammatory response that thickens the artery walls with resultant
renal ischemia. Renal ischemia, in turn, can further damage the kidney
through the renin-angiotensin response and its resultant exacerbation
of hypertension.
Glomerular hypertension is normally an adaptive mechanism in
remaining nephrons to increased workload resulting from nephron loss,
whatever the cause. This sustained intraglomerular hypertension
increases mesangial matrix production and leads to glomerulosclerosis
by ECM accumulation. The process is mediated by TGF-ß in the first
place, with a contribution of angiotensin II, PDGF, CSGF and
endothelins. Systemic and glomerular hypertension are not necessarily
associated, as glomerular hypertension may precede systemic
hypertension in glomerular disease.
Diabetic Nephropathy
Diabetes is a disease in which your body does not make enough insulin
or cannot use normal amounts of insulin properly. This results in a high
blood sugar level, which can cause problems in many parts of your
body. Diabetes is the leading cause of kidney disease. Diabetic
nephropathy(DN) is now the commonest cause of end-stage renal
failure in the western world. The key pathophysiologic event in diabetic
nephropathy is basement membrane (BM) damage. With renal
damage, there is progressive thickening of the BM , pathologic change
in mesangial and vascular cells, formation of AGES, accumulation of
polyols via the aldose reductase pathway, and activation of protein
kinase C. Passage of macromolecules through the BM may also
activate inflammatory pathways that contribute to the damage
secondarily.
The renal hemodynamic abnormality is similar in type 1 and type 2
diabetes. An early physiologic abnormality is glomerular hyperfiltration
associated with intraglomerular hypertension. This is accompanied by
the onset of microalbuminuria, the first practical evidence of renal
involvement in diabetes. A clinically asymptomatic period of decline
follows, with progression of microalbuminuria to
macroalbuminuria( >300mg albumin per day), Once this occurs , renal
function falls at a significant but variable rate. The rate of decline
depends on type of diabetes, genetic predisposition, glycemic control,
and very importantly, blood pressure. Later stages may be
accompanied by clinically significant albuminuria, edema, and
nephritic syndrome.
Proteinuria and tubulointerstitial damage. Proteinuria can damage
tubulointerstitium through multiple pathways including direct tubular
toxicity, changes in tubular epithelial metabolism, induced cytokine
and chemokine synthesis, and increased expression of adhesion
molecules. in tubular epithelial metabolism, induced cytokine and
chemokine synthesis, andincreased expression of adhesion molecules.
(Abbate). Excess protein reabsorptionin proximal tubule may exceed
lysosomal processing capacity, lead to lysosomal
rupture and result in direct tubular toxicity. There is a great variability
in tubular
toxicity induced by proteinuria. For example, patients with nephrotic
range proteinuria exclusively consisting of albuminuria as in minimal
change disease, rarely exhibit tubulointerstitial damage.
Generally, Regardless of the etiology, chronic kidney disease is
characterized by renal fibrosis - glomerulosclerosis and
tubulointerstitial fibrosis. The impairment of the tubulointerstitium
(tubulointerstitial fibrosis and tubular atrophy) is at least as important
as that of the glomeruli (glomerulosclerosis). There is a common
consensus that the severity of tubulointerstitial injury correlates closely
(and better than glomerular injury) with long-term impairment of renal
function. This is not surprising, considering that tubules and
interstitium occupy more than 90% of the kidney volume. As very
recently summarized by Fine and Norman, tubulointerstitial fibrosis
encompasses a number of characteristic features including an
inflammatory cell infiltrate which results from both activation of
resident inflammatory cells and recruitment of circulating
inflammatory cells; an increase in interstitial fibroblasts due to
increased proliferation and decreased apoptosis of resident interstitial
cells, as well as recruitment of cells to the tubulointerstitium; the
appearance of myofibroblasts expressing the cytoskeletal protein α-
smooth muscle actin, which arise by differentiation of resident
interstitial fibroblasts and infiltrating cells and via transdifferentiation;
accumulation of extracellular matrix (ECM) as the net result of
increased synthesis of ECM components and decreased ECM
degradation, mostly by specific metalloproteinases that are under the
control of specific inhibitors; tubular atrophy as a consequence of
apoptosis and epithelial–mesenchymal transdifferentiation (EMT); and
rarefaction of peritubular capillaries. It has been shown lately that
hypoxia-inducible factor-1 (HIF-1), considered to be master
regulator of the adaptive response controlling expression of hundreds
of genes, also stimulates EMT, which explains why hypoxia results in
fibrosis and progressive renal failure. Hypoxia as a consequence of
peritubular capillaries loss has been frequently observed in chronic
kidney disease

Pathophysiology and Clinical features

. -Bone abnormalities due to :

a) Decreased GFR increase in blood phosphorous which results in
phosphorous complexes with Ca in blood leading to hypo
calcemia
b) Normal response in hypocalcemia requires 1,25,OH vit D. Since
kidneys are not working no/decreased hydroxylation of Vit D
leading osteomalacia.
c) The second component of the response is PTH, which causis bone
resorption leading to osteotitis fibrosis.
d) In acidosis H are buffered by bone leading to chewing up of bone
by H.

Anemia caused by:

a) decreased Erythropoetin production by the kidneys.
b) urotoxemia causing decreased RBC survival
c) GI irritation by urotoxins causing GI bleeds.
d) improper platelet function due to urotoxins enhances the GI
blood and other bleeds.

Azotaemia/Uraemia

Defined as raised plasma level of nitrogenous molecules. Urea can

cause troublesome GI symptoms and may be responsible for the
capillary fragility and purpura(bruising) seen in renal patients.

Fluid and Electrolyte imbalance

Urine concentration ability is often diminished in the early stage s
causing dilute polyuria and the risk of dehydration and electrolyte
depletion, as in polyuric phase of ARF. In the latter stages urine volume
falls and the consequent retention of sodium and water is the main
cause of hypertension usually found in CRF patients.
Dermatological Complications
 Hyperpigmentation
 Abnormal perspiration
 Dryness
 Persistent puritus
 Hyperparathyroidism, hypervitaminosisA, and dermal mast cell
proliferation with subsequent histamine release have been
suggested as cause of pruritus.

Other features: The immune system is com promised, atherogenic

lipid levels rise and pericarditis sometimes occurs.

Other Renal Diseases

Polycystic Kidney Disease
There are two types of PKD. The autosomal dominant PKD or ADPKD
and the autosomal recessive PKD or ARPKD. IN this disease, cysts or
fluid-filled pouches are found primarily in the kidney but they can
affect other organs, e.g liver, pancrease, spleen and ovary.
Recent evidence suggests that the primary abnormality leading to cyst
formation in both the autosomal dominant and recessive forms of PKD
is related to defects in cilia-mediated signaling activity.40 Specifically,
PKD is thought to result from defects in the primary cilium, an
immotile, hair-like cellular organelle present on the surface of most
cells in the body, anchored in the cell body by the basal body.40,64 In
the kidney, primary cilia have been found to be present on most cells
of the nephron, projecting from the apical surface of the renal
epithelium into the tubule lumen.64 In response to fluid flow over the
renal epithelium, the primary cilium is bent, resulting in a flow-induced
increase in intracellular calcium. About 50% of patients with PKD will
have kidney failure by age 60yrs and about 60% by age 70.

Nephritic syndrome
The hallmark of nephritis are renal impairment with oliguria, sodium
and fluid retention, and oedema, mild to moderate proteinuria(less
than 1g/24h) and possibly haematuria. Urinary red blood cell casts are
diagnostic. Frequently there are no further complications but
hypertension, hypertensive encephalopathy and pulmonary oedema
may occur. Serum creatinine is moderately elevated but only rarely
does oliguric ARF supervene. Acute GN following a non-renal
streptococcal infection is the commonest form.

Nephrotic Syndrome
Nephrotic Syndrome is characterized by hypoalbuminemia, urine
protein excretion more than 3.5 gm/day, hyperlipidemia, lipiduria and
edema. The heavy proteinuria is a result of damage to the
permselective barrier of the glomerulus. The etiologies of nephritic
syndrome are multiple and diverse. The cause can be
idiopathic( primary glomerular disease ), or secondary to chronic
systemic disease (e.g diabetes mellitus, amyloidosis, sickle cell
anemia, lupus), Cancer(e.g multiple myeloma, Hodgkin’s disease),
infections( e.g HIV, Hepatitis B, syphilis, malaria) intravenous(IV) drug
abuse, and medications[ gold, penicillamine, captopril, nonsteroidal
anti-inflammatory drugs(NSAIDS)]