Renal ciliopathy

Renal ciliopathy is a broad group of rare genetic disorders caused by defects in the structure or function of cilia — tiny hair-like projections on the surface of kidney cells that play critical roles in cellular signaling and fluid sensing. These disorders primarily affect the kidneys but frequently involve other organ systems, reflecting the widespread importance of cilia throughout the body. Renal ciliopathies encompass a spectrum of conditions including nephronophthisis, autosomal dominant and autosomal recessive polycystic kidney disease, Bardet-Biedl syndrome, Joubert syndrome with renal involvement, and Meckel-Gruber syndrome, among others. The hallmark renal features include cyst formation, progressive tubulointerstitial fibrosis, and decline in kidney function that can lead to end-stage renal disease (ESRD). Depending on the specific subtype, extrarenal manifestations may include retinal degeneration (retinitis pigmentosa), liver fibrosis, cerebellar malformations, skeletal anomalies (polydactyly), obesity, intellectual disability, and situs inversus. The age of onset and severity vary widely depending on the specific genetic cause, ranging from severe prenatal or neonatal presentations (such as Meckel-Gruber syndrome) to slowly progressive kidney disease presenting in adolescence or adulthood. Renal ciliopathies are caused by mutations in a large and growing number of genes encoding ciliary proteins, including but not limited to NPHP1, PKD1, PKD2, PKHD1, BBS genes, and CEP290. Inheritance is most commonly autosomal recessive, though autosomal dominant forms exist (notably autosomal dominant polycystic kidney disease). There is currently no cure for renal ciliopathies. Treatment is largely supportive and includes management of hypertension, slowing progression of chronic kidney disease, renal replacement therapy (dialysis or kidney transplantation) for ESRD, and addressing extrarenal complications. Tolvaptan has been approved for autosomal dominant polycystic kidney disease to slow cyst growth and kidney function decline. Genetic counseling is recommended for affected families.

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