Polycystic kidney disease (PKD)
D E FI N I T ION
Autosomal dominant inherited disorder characterized by the development of
multiple renal cysts that gradually expand and replace normal kidney substance, variably
associated with extrarenal (liver and cardiovascular) abnormalities.
AE T IOLOGY
Eighty five percent are mutations in PKD1 (polycystin-1) on chromosome 16,
a membrane-bound multidomain protein involved in cell–cell and cell–matrix interactions;
15% are mutations in PKD2 (polycystin-2) on chromosome 4, a Ca2þ
permeable
cation channel.
Pathological process is considered to be a proliferative/hyperplastic abnormality of the tubular
epithelium. In early stages, cysts are connected to the tubules from which they arise and
the fluid content is glomerular filtrate. When cyst diameter>2 mm, most detach from the
patent tubule and the fluid content is derived from secretions of the lining epithelium.
With time, cysts enlarge and cause progressive damage to adjacent functioning
nephrons.
E P IDEMIOLOGY
Most commonly inherited kidney disorder affecting one in 800, responsible
for nearly 10% of end-stage renal failure in adults.
H ISTORY
Usually present at 30–40 years. Twenty percent have no family history.
May be asymptomatic.
Pain in flanks as a result of cyst enlargement/bleeding, stone, blood clot migration,
infection.
Haematuria (may be gross).
Hypertension.
Associated with intracranial ‘berry’ aneurysms and may present with subarachnoid haemorrhage:
sudden onset headache.
EXAMINA T I ON
Abdominal distension, enlarged cystic kidneys and liver palpable, hypertension.
Signs of chronic renal failure at late stage.
Signs of associated aortic aneurysm or aortic valve disease.
INVE S T I G A T IONS
Ultrasound or CT imaging: Multiple cysts observed bilaterally in enlarged
kidneys, sensitivity of detection poor for those <20 years. Liver cysts may also be
seen.
MANAGEMENT
Blood pressure control: Slows the rate of decline in renal function and
minimizes the risk of rupture of a cerebral aneurysm. ACE inhibitors can effectively # blood
pressure and minimize the degree of secondary glomerular injury by # intraglomerular
pressure.
Haematuria: Managed conservatively.
Infections: Prompt treatment with non-nephrotoxic antibiotics (ciprofloxacin or co-trimoxazole).
Avoid the use of NSAIDs.
End-stage renal failure: (see renal failure, chronic).
Consider screening for intracranial aneurysm if family history of aneurysm.
Surgery: Cyst decompression reserved for selected cases. Liver cyst aspiration, marsupialization
or resection if gives rise to pain.
Genetic counselling.
COM P L IC A T I ONS
Chronic renal failure, renal stones (20%).
1–2% suffer subarachnoid haemorrhage/intracerebral bleed.
Cysts develop in the liver (70%) and pancreas (10%) but these rarely cause organ dysfunction.
Mitral valve prolapse, diverticulosis of the colon.
PROGNOSIS
Fifty percent develop end-stage renal failure by age 60 years. Renal replacement
therapy prolongs life by 15 years (mean). Patients with hypertension are much more
likely to develop progressive renal failure.
NEPHROLOGY 125
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