Genetic renal abnormalities

Inherited disorders of renal structure and function are relatively common causes of end-stage renal disease requiring renal replacement therapy. A family history of haematuria, urinary tract infection or renal failure can alert the clinician to the possible diagnosis of underlying renal genetic abnormalities. In practice, autosomal dominant polycystic kidney disease (ADPKD) is the commonest inherited renal disorder with well-recognized clinical features of multiple kidney cysts associated with hypertension and renal failure. Insights into the cell biology of ADPKD are yielding new therapeutic approaches to limit cyst growth and prevent progressive renal failure. Microscopic haematuria is a clinical finding that presents a diagnostic challenge because it has multiple possible aetiologies. Mutations in the genes encoding collagen proteins within the glomerular basement membrane (GBM) can disrupt its normal barrier function. Thin basement membrane nephropathy is a relatively common cause of familial haematuria, caused by GBM collagen gene mutations, that normally has a good long-term prognosis. Alport’s syndrome is a rare and genetically heterogeneous condition leading to renal failure in men inheriting the X-linked gene defect. Single gene defects may cause diverse renal tubular disorders such as predisposition to renal calculi, diabetes insipidus, renal tubular acidosis or hypertension with associated electrolyte imbalance. Gene mutations responsible for familial renal cancer syndromes, such as tuberous sclerosis complex and von Hippel Lindau disease, have also been identified.