Definition, Etiology, PathogenesisTop
Autosomal dominant tubulointerstitial kidney disease (ADTKD), formerly medullary cystic kidney disease (MCKD) or familial juvenile hyperuricemic nephropathy, is a rare adolescent-onset or adult-onset condition leading to progressive chronic kidney disease and end-stage kidney disease caused by mutations in either UMOD, MUC1, or REN. Tubulointerstitial fibrosis and bland urine (absence of hematuria or proteinuria) are hallmarks of ADTKD, but small medullary cysts may also be present.
ADTKD-UMOD is the most common form of ADTKD, caused by mutations in uromodulin (Tamm-Horsfall mucoprotein), the most abundant protein in normal urine and hyaline casts. Patients often develop gout as early as adolescence. ADTKD-MUC1 is caused by mutations in mucin 1 and has a similar presentation as ADTKD-UMOD, but gout is often later in onset. ADTKD-REN is the rarest form of ADTKD, caused by mutations in the renin signal sequence leading to hyperkalemia, hypotension, anemia, and increased propensity to acute kidney injury.
There is no specific treatment for ADTKD. Hyperuricemia may be treated with allopurinol in ADTKD-UMOD or ADTKD-MUC1, and symptomatic hypotension may be treated with a high-salt diet or fludrocortisone in ADTKD-REN1. End-stage kidney disease requiring renal replacement therapy typically develops between the ages of 20 and 70 years.