Serum uromodulin is a novel renal function marker in the Japanese population
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ORIGINAL ARTICLE
Serum uromodulin is a novel renal function marker in the Japanese population Ryosuke Usui1 · Tetsuya Ogawa2 · Hideo Takahashi3 · Chihiro Iwasaki1 · Minako Koike1 · Taku Morito4 · Michiyasu Hatano4 · Kosaku Nitta5 Received: 9 June 2020 / Accepted: 27 August 2020 © Japanese Society of Nephrology 2020
Abstract Background Uromodulin, also known as Tamm–Horsfall protein, is the most abundant protein in urine. It has recently been reported that uromodulin exists in a small amount in blood and that its concentration correlates with the estimated glomerular filtration rate (eGFR). Methods First, we generated anti-human uromodulin mouse monoclonal antibodies (mAb(s)) and established a specific enzyme-linked immunosorbent assay (ELISA) for uromodulin. We then performed an observational clinical study to determine if there was a correlation between serum uromodulin concentration and estimates of kidney function and whether the serum uromodulin value could be a biomarker in clinical nephrology. The clinical study included 308 patients with and without chronic kidney disease and healthy volunteers. Serum concentrations of creatinine, cystatin C, and uromodulin were measured and correlations were sought between the eGFR calculated from the creatinine and cystatin C levels and the serum uromodulin concentration. Results There was a good correlation between the serum uromodulin concentration and the eGFR value calculated from the creatinine (r = 0.76) and cystatin C (r = 0.79) levels. The mean serum uromodulin level in the group with an eGFR > 90 mL/ min/1.73 m2 calculated using cystatin C was significantly higher than that in the group with an eGFR of 80–89 mL/ min/1.73 m2. Conclusions The serum uromodulin measurement could be a useful biomarker for identification of patients with early deterioration of kidney function. Keywords Uromodulin · Tamm–horsfall protein · Kidney function · CKD · Biomarker
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10157-020-01964-y) contains supplementary material, which is available to authorized users. * Ryosuke Usui [email protected] 1
Division of Nephrology, Department of Medicine, Yachiyo Medical Center, Tokyo Women’s Medical University, 477‑96 Owadashinden, Yachiyo city, Chiba 276‑8524, Japan
2
Department of Medicine, Tokyo Women’s Medical University Medical Center East, Tokyo, Japan
3
Minami-Akatsuka Clinic, Ibaraki, Japan
4
Department of Medicine, Division of Nephrology, Yokohama Rosai Hospital, Kanagawa, Japan
5
Department of Medicine, Kidney Center, Tokyo Women’s Medical University, Tokyo, Japan
Uromodulin is isolated as a highly glycosylated mucoprotein that inhibits viral hemagglutination, is exclusively expressed in the kidney, and is the most abundant protein in urine [1]. Almost all of the uromodulin in the kidney is released from the luminal surface of tubular epithelial cells between the thick ascending limb of Henle’s loop and the early distal convoluted tubule. Uromod
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