Autosomal Dominant Tubulointerstitial Kidney Disease

Highlights

• There are 3 primary causes of autosomal dominant tubulointerstitial kidney disease (ADTKD): mutations in the UMOD gene encoding uromodulin (Tamm-Horsfall glycoprotein), mutations in the REN gene encoding renin, and mutations in the MUC1 gene encoding mucin-1.

• These conditions should be suspected if both a parent and child have kidney disease and if the urinalysis reveals a bland sediment.

• In all 3 conditions, there is a variable rate of progression of CKD, with the age of onset of end-stage kidney disease ranging from 17 to >75 years.

• These conditions should be diagnosed by genetic testing and not by kidney biopsy.

• In patients with ADTKD-REN, a low sodium diet should be avoided, and a high sodium diet or fludrocortisone should be considered as treatments.

There are 3 major forms of autosomal dominant tubulointerstitial kidney disease (ADTKD): ADTKD due to UMOD mutations, MUC1 mutations, and mutations in the REN gene encoding renin. Lack of knowledge about these conditions contributes to frequent nondiagnosis, but with even limited knowledge, nephrologists can easily obtain a diagnosis and improve patient care. There are 3 cardinal features of these disorders: (1) the conditions are inherited in an autosomal dominant manner and should be considered whenever both a parent and child suffer from kidney disease; the presence of even more affected family members provides further support. (2) These conditions are associated with a bland urinary sediment, ruling out glomerular disorders. (3) There is a variable rate of decline in kidney function. The mean age of ESRD is approximately 45, but the range is from 17 to >75. ADTKD-UMOD is often but not always associated with gout in the teenage years. ADKTKD-REN is associated with signs of hyporeninemia: mild hypotension, mild hyperkalemia, anemia in childhood, and hyperuricemia and gout in the teenage years. The only clinical manifestation of ADTKD-MUC1 is slowly progressive CKD. Diagnosis should be made by genetic testing, and kidney biopsy should be avoided.