الرحيم الرحمن الله بسم

POLYCYSTIC KIDNEY DISEASE

Lecture by:Dr. Zaidan Jayed Zaidan

Adult polycystic kidney disease (PKD) is a common condition (prevalence ∼1:1000) that is inherited as an autosomal dominant trait. Small cysts lined by tubular epithelium develop from infancy or childhood and enlarge slowly and irregularly. Surrounding normal kidney tissue is progressively attenuated. Renal failure is associated with grossly enlarged kidneys .

Mutations in PKD1 account for 85% of cases and PKD2 for about 15%. ESRF occurs in ∼50% of patients with PKD1 mutations with a mean age of onset of 52 years, but in a minority of patients with PKD2 mutations with a mean age of onset of 69 years. Other genes are responsible rarely .

Clinical features

Affected subjects are usually asymptomatic until later life. After the age of 20 there is often insidious onset of hypertension. One or both kidneys may be palpable and the surface may be nodular. There is then a gradual reduction in renal function .

ASSOCIATION1)About 30% of patients with PKD

have hepatic cysts, but disturbance of liver function is rare. Sometimes (almost always in women) this causes massive and symptomatic hepatomegaly, usually concurrent with renal enlargement, but occasionally with only minor renal involvement .

ASSOCIATION2)Berry aneurysms of cerebral

vessels are an associated feature, and about 10% of patients have a subarachnoid haemorrhage. This feature appears to be largely restricted to certain families (and presumably specific mutations). 3)Mitral and 4) aortic regurgitation are frequent but rarely severe, and 5)colonic diverticula and 6)abdominal wall hernias may occur .

PKD is not a pre-malignant condition. The rate of renal malignancy is no different from that of other patients with renal failure (but is higher than the general population) .

Investigations and screening

The diagnosis is usually based on family history, clinical findings and ultrasound. 1)Ultrasound demonstrates cysts in ∼95% of affected patients over the age of 20, but may not detect small developing cysts in younger patients. It is important to identify multiple cysts, not just two or three.

Investigations and screening

2)Now that the gene defects responsible for PKD have been identified, it is sometimes possible to make a specific genetic diagnosis, but the genes involved are particularly difficult because of their size, the existence of a closely related PKD1 pseudogene, and the wide variety of mutations which affect different families. Occasionally, linkage analysis may be used to exclude the diagnosis in a young adult with normal renal imaging.

Investigations and screening

3)Screening for intracranial aneurysms is not generally indicated. Where non-invasive MR angiography is available, some centres screen patients in families with a history of subarachnoid haemorrhage. However, even then, the yield of screening has been low, and the risk-benefit ratio of intervention in asymptomatic aneurysms in this disease is not known .

Management Nothing has yet been found to alter the

rate of progression of renal failure in human PKD, although there are some potentially interesting approaches under investigation. Good control of blood pressure is important because cardiovascular morbidity and mortality are so common in renal disease, but there is no evidence that control of moderate hypertension retards the development of renal failure in PKD, in contrast to the evidence for glomerular diseases .

Patients with PKD are usually good candidates for dialysis and transplantation. Sometimes kidneys are so large that one or both have to be removed to make space for a renal transplant .

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