title: Hints to the diagnosis of uromodulin kidney disease.
abstract: BACKGROUND
  Uromodulin kidney disease (UKD) is an inherited kidney disease caused by a uromodulin (UMOD) gene mutation. The UMOD gene encodes the Tamm-Horsfall protein (THP), which is the most abundant protein in healthy human urine. Because of its rarity, the incidence of UKD has not been fully elucidated. The purpose of the present study is to clarify the frequency of UKD among patients who underwent renal biopsy.
  
  
  METHODS
  Immunostaining for THP was performed for patients <50 years of age with renal insufficiency and hyperuricemia without overt urinalysis abnormality from renal biopsy databases. Serum and urinary THP concentrations were evaluated in available individuals.
  
  
  RESULTS
  Fifteen patients were selected for immunostaining from a total of 3787 patients. In three independent patients, abnormal THP accumulation in renal tubular cells was observed. A novel missense A247P UMOD mutation was detected in two of the three patients, including one having a typical family history of familial juvenile hyperuricemic nephropathy. Serum and urinary THP concentrations of all available patients with UMOD A247P mutation were significantly lower than those of controls.
  
  
  CONCLUSIONS
  In the present study, UKD was detected in <1 in 1000 subjects who underwent renal biopsies. However, in subjects meeting all of the above criteria, abnormal THP accumulation was detected in 20% (3/15), suggesting that renal biopsy with immunostaining for THP is a good tool for diagnosing UKD. Also, low serum THP concentration detected in the present subjects might be a good diagnostic marker or important in understanding the pathogenesis of UKD.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine , Kanazawa University Graduate School of Medicine , Kanazawa , Japan.
authors.forename: Tamehito
authors.initials: T
authors.lastname: Onoe
authors.affiliation: Division of Rheumatology, Department of Internal Medicine , Kanazawa University Graduate School of Medicine , Kanazawa , Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Division of Rheumatology, Department of Internal Medicine , Kanazawa University Graduate School of Medicine , Kanazawa , Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Mizushima
authors.affiliation: Division of Rheumatology, Department of Internal Medicine , Kanazawa University Graduate School of Medicine , Kanazawa , Japan.
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Ito
authors.affiliation: Division of Rheumatology, Department of Internal Medicine , Kanazawa University Graduate School of Medicine , Kanazawa , Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kawakami
authors.affiliation: Department of Nephrology , Daimon Clinic for Internal Medicine, Nephrology and Dialysis , Nonoichi , Japan.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Daimon
authors.affiliation: Department of Internal Medicine , Japan Community Health Care Organization, Kanazawa Hospital , Kanazawa , Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Muramoto
authors.affiliation: Third Department of Internal Medicine , University of Fukui Faculty of Medical Sciences , Eiheiji , Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Konoshita
authors.affiliation: Division of Cardiology, Department of Internal Medicine , Kanazawa University Graduate School of Medicine , Kanazawa , Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamagishi
authors.affiliation: Division of Rheumatology, Department of Internal Medicine , Kanazawa University Graduate School of Medicine , Kanazawa , Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kawano
keywords: CKD; Tamm–Horsfall protein; familial juvenile 2; hyperuricemic nephropathy; kidney biopsy; uromodulin