Genetic renal disorders and genomic screening of renal disease

Abstract

Genetic kidney disease (GKD) accounts for 10–15% of end-stage kidney disease (ESKD). The introduction of next-generation genomic sequencing has improved the diagnostic yield for pathogenic gene variants associated with GKD and is increasingly available to UK clinicians. An early disease onset, family history and extra-renal features are useful but not essential criteria for diagnosing GKD. Autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic cause of ESKD, is characterized by cyst development, hypertension and progressive chronic kidney disease (CKD). ADPKD is most often caused by PKD1 pathogenic variants, which are associated with earlier onset of ESKD. Tolvaptan is licensed for use in ADPKD as it slows cyst growth and the consequent decline in kidney function. Autosomal dominant tubulo-interstitial kidney disease is characterized by tubulo-interstitial fibrosis and bland urine, which is often mislabelled as CKD of uncertain aetiology or hypertensive nephropathy. UMOD is one of five causative genes, for which early-onset gout is an important phenotypic feature. Alport syndrome is a type IV collagenopathy with clinical features ranging from isolated haematuria to progressive CKD with hearing loss. Over 50 pathogenic gene variants have been associated with renal tubulopathies, causing salt, water and electrolyte imbalance.