Uromodulin kidney disease (UKD) is a subtype of autosomal dominant tubulointerstitial kidney disease (ADTKD), and is a rare cause of renal failure and gout in young people.
ADTKD-<i>UMOD</i>, which is associated with retention of mutant uromodulin in the endoplasmic reticulum (ER) of renal thick ascending limb cells, is characterized by hyperuricemia, interstitial fibrosis, inflammation and renal failure, and we used targeted homologous recombination to generate a knock-in mouse model with an ADTKD-causing missense cysteine to arginine uromodulin mutation (C125R).
We speculated that he had MCKD type 1 on the basis of the late onset of renal failure and no significant evidence of mutation in the UMOD gene that is associated with MCKD type 2.
A renewed interest in UMOD has been triggered by the identification of UMOD mutations as cause of hereditary dominant renal diseases, now referred to as uromodulin-associated kidney diseases (UAKDs), presenting with tubulointerstitial fibrosis, defective urinary concentration, hyperuricaemia and gout, and progressive renal failure.
In a single-center renal clinic, we have established routine mutation testing to diagnose UMOD-associated kidney disease (UAKD), an autosomal dominant disorder typically characterized by gout, hyperuricemia, and renal failure in the third to sixth decades.
Herein is demonstrated that patients with FJHN and renal insufficiency exhibit a profound reduction in urinary uromodulin together with either elevated or decreased plasma uromodulin.
When a mutation is found, family members can be tested for a UMOD mutation and pre-symptomatic diagnosis may allow counseling to prevent or halt the progression to renal insufficiency.
Autosomal-dominant medullary cystic kidney disease type 2 (MCKD2) and familial juvenile hyperuricemic nephropathy (FJHN) are heritable renal diseases with autosomal-dominant transmission and shared features, including polyuria, progressive renal failure, and abnormal urate handling, which leads to hyperuricemia and gout.
Familial juvenile hyperuricemic nephropathy (FJHN [MIM 162000]) is an autosomal-dominant disorder characterized by abnormal tubular handling of urate and late development of chronic interstitial nephritis leading to progressive renal failure.
The disease complex medullary cystic disease/familial juvenile hyperuricemic nephropathy (MCKD/FJHN) is characterized by alteration of urinary concentrating ability, frequent hyperuricemia, tubulo-interstitial fibrosis, cysts at the cortico-medullary junction and renal failure.