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Renal involvement in genetic disease 

Renal involvement in genetic disease

Renal involvement in genetic disease

D Joly

and J P Grünfeld



Autosomal dominant polycystic kidney disease (ADPKD)—discussion of therapies designed to modify the disease process, e.g. somatostatin analogues, mammalian target of rapamycin (mTOR) inhibitors, vasopressin (V2) receptor antagonists.

Expanded discussion of genetic causes of familial focal segmental glomerulosclerosis and other familial primary glomerulonephritis, also of the syndrome caused by renin gene mutation.

Updated on 25 May 2011. The previous version of this content can be found here.
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date: 30 March 2017

There are many inherited disorders in which the kidney is affected: this chapter is concerned with the commonest inherited diseases leading to renal failure.

Autosomal dominant polycystic kidney disease—accounts for about 7% of cases of endstage renal failure in Western countries. Inheritance is autosomal dominant, with mutations in polycystin 1 responsible for 85% of cases and mutations in polycystin 2 accounting for most of the remainder, these being transmembrane proteins that are able to interact, function together as a nonselective cation channel, and also induce several distinct transduction pathways. May present with renal pain, haematuria, urinary tract infection, or hypertension, or be discovered incidentally on physical examination or abdominal imaging, or by family screening, or after routine measurement of renal function. Commonly progresses to endstage renal failure at between 40 and 60 years of age. Extrarenal manifestations include intracranial aneurysms, liver cysts, and mitral valve prolapse.

Alport’s syndrome—X-linked dominant inheritance in 85% of kindreds, with molecular defect involving the gene encoding for the α‎-5 chain of the type IV collagen molecule. Males typically present with macroscopic haematuria in childhood, followed by permanent microscopic haematuria, and later by proteinuria and renal failure. Extrarenal manifestations include perceptive deafness of variable severity, ocular abnormalities (bilateral anterior lenticonus is pathognomonic), and (uncommonly) macrothrombocytopenia. Carrier women often have slight or intermittent urinary abnormalities, but may develop mild impairment of renal function late in life, and a few develop endstage renal disease. In the autosomal recessive form of Alport’s syndrome, renal disease progresses to endstage before 20 to 30 years of age at a similar rate in both affected men and women.

Nephronophthisis—the most common genetic cause of endstage renal disease in children and young adults, this is a group of autosomal recessive tubulointerstitial nephropathies with multiple small medullary cysts that appear late in the course of the disease. Eighty per cent of cases are caused by homozygous deletions of the NPH1 gene, which codes for nephrocystin. Present with polyuria, polydipsia, and growth retardation in early childhood, progressing to endstage renal disease at a mean age of 14 years.

von Hippel–Lindau disease—due to mutation in the tumour suppressor gene VHL; renal cysts and bilateral multifocal renal cell carcinomas are found in 70% of cases. Carcinomas are often asymptomatic, should be screened for regularly, and occur at a mean age of 45 years.

Tuberous sclerosis—due to mutation of genes encoding for hamartin (TSC1) or tuberin (TSC2); characterized by renal angiomyolipomas, which are benign, often multiple and bilateral.

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