Genetic disorders of renal structure and function are recognized causes of end-stage renal disease (ESRD) requiring renal replacement therapy. A family history of haematuria, urinary tract infection or ESRD can prompt the clinician to consider an underlying renal genetic disorder. In practice, the most common inherited renal condition is autosomal dominant polycystic kidney disease (ADPKD), characterized by multiple kidney cysts associated with hypertension and later progression to chronic kidney disease (CKD). Insights into the cell biology of ADPKD have resulted in new therapy to limit cyst growth and slow the progression of CKD. Non-visible haematuria can present a diagnostic challenge because it has so many possible causes. Mutations in genes encoding collagen proteins within the glomerular basement membrane can disrupt its normal barrier function. Thin basement membrane nephropathy, caused by glomerular basement membrane collagen gene mutations, can cause familial haematuria that normally has a good long-term prognosis. Alport’s syndrome is a rarer and genetically heterogeneous condition classically leading to CKD associated with sensorineural deafness in men inheriting an X-linked gene defect. Single-gene defects can also cause diverse renal tubular disorders, such as predisposition to hypertension with associated electrolyte imbalance, renal calculi, renal tubular acidosis or diabetes insipidus. Gene mutations responsible for familial renal cancer syndromes, such as tuberous sclerosis complex, Birt–Hogg–Dubé syndrome and von Hippel–Lindau disease, are rare but important to recognize so that long-term surveillance for cancers is commenced.
- Alport syndrome
- polycystic kidney disease