Furthermore, the genetic basis of familial juvenile hyperuricemic nephropathy (FJHN), glomerulocystic kidney disease (GCKD) and autosomal dominant medullary cystic kidney disease 2 (MCKD2) has been recently attributed to mutations within the THP gene.
Despite the unique location and recent association of THP gene mutations with hereditary uromodulin-associated kidney disease and THP single nucleotide polymorphisms with chronic kidney disease and hypertension, the physiological function(s) of THP and its pathological involvement remain incompletely understood.
However, UMOD, REN or HNF-1β mutations are found in only approximately 45% of FJHN probands, indicating the involvement of other genetic loci in approximately 55% of probands.
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.
We characterized tubular expression of uromodulin and the ER stress surrogate marker Grp78 by immunohistochemistry in kidney biopsy specimens from 7 patients with UMOD-related kidney disease.
Therefore, THGP modulation of ROMK function confers a new role of THGP on renal ion transport and may contribute to salt wasting observed in FJHN/MCKD-2/GCKD patients.
Multiple names have been proposed for these disorders, including 'Medullary Cystic Kidney Disease (MCKD) type 2', 'Familial Juvenile Hyperuricemic Nephropathy (FJHN)', or 'Uromodulin-Associated Kidney Disease (UAKD)' for UMOD-related diseases and 'MCKD type 1' for the disease caused by MUC1 mutations.
Autosomal-dominant juvenile hyperuricemia, gouty arthritis, medullary cysts, and progressive renal insufficiency are features associated with familial juvenile hyperuricemic nephropathy (FJHN), medullary cystic kidney disease type 1 (MCKD1) and type 2 (MCKD2).
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.
Recent reports on the discovery of mutations of the uromodulin (UMOD) gene in families with FJHN encouraged us to screen UMOD mutations in Japanese families with FJHN, including family 1.
Umod mutant mice exhibit increased plasma urea and Cystatin levels, impaired urinary concentration ability, reduced fractional excretion of uric acid and nephropathological alterations including uromodulin retention in TALH cells, interstitial fibrosis and inflammatory cell infiltrations, tubular atrophy and occasional glomerulo- und tubulocystic changes, a phenotype highly similar to UAKD in humans.
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.
In contrast, recently, another group described mutations in the UMOD gene as responsible for MCKD2 and familial juvenile hyperuricemic nephropathy (FJHN).
Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons.