Autosomal Dominant Tubulointerstitial Kidney Disease (ADTKD)

Definition, Etiology, PathogenesisTop

Autosomal dominant tubulointerstitial kidney disease (ADTKD), formerly medullary cystic kidney disease or familial juvenile hyperuricemic nephropathy, is a rare adolescent-onset or adult-onset condition leading to progressive chronic kidney disease (CKD) and kidney failure, caused by pathogenic variants in either UMOD, MUC1, REN, or HNF1B. Tubulointerstitial fibrosis and bland urine (absence of hematuria or proteinuria) are hallmarks of ADTKD. Hyperuricemia and small medullary cysts may be present.

ADTKD-UMOD is the most common form of ADTKD, caused by variants in uromodulin (Tamm-Horsfall mucoprotein), the most abundant protein in normal urine and hyaline casts. Patients often develop gout as early as adolescence, and kidney failure may occur in the second or third decade of life. ADTKD-MUC1 is caused by a variable number tandem repeat (VNTR) in the mucin 1 promoter. ADTKD-REN is the rarest form of ADTKD, which is caused by pathogenic variants in the renin signal sequence and leads to hyperkalemia, hypotension, anemia, and increased propensity to acute kidney injury. ADTKD-HNF1B may be associated with hypomagnesemia, pancreatic insufficiency, autism, and maturity-onset diabetes of the young (MODY).

TreatmentTop

There is no specific treatment for ADTKD beyond standard CKD care. Hyperuricemia may be treated with allopurinol, and symptomatic hypotension, with a high-salt diet or fludrocortisone in ADTKD-REN1.