Urinary glycated uromodulin in diabetic kidney disease
Journal
Clinical Science
Journal Volume
131
Journal Issue
15
Pages
1815 - 1829
Date Issued
2017
Author(s)
Chang, Chia-Chu
Chen, Chen-Yu
Huang, Ching-Hui
Wu, Chia-Lin
Wu, Hung-Ming
Chiu, Ping-Fang
Kor, Chew-Teng
Chen, Ting-Huan
Kuo, Cheng-Chin
Wen, Hui-Chin
Huang, Chih-Yang
Chang, Chung-Ho
Abstract
Advanced glycation end-products (AGEs) form during oxidative stress, which is increased in diabetes mellitus (DM). Uromodulin is a protein with a renal protective effect, and may be subject to glycation. The implications of uromodulin glycation and AGEs in the urine are not understood. Here, immunoprecipitation and liquid chromatography-mass spectrometry identified glycated uromodulin (glcUMOD) in the urine of 62.5% of patients with diabetic kidney disease (DKD), 20.0% of patients with non-diabetic chronic kidney disease (CKD), and no DM patients with normal renal function or healthy control participants; a finding replicated in a larger cohort of 84 patients with CKD in a case-control study (35 with DM, 49 without). Uromodulin forms high molecular weight polymers that associate with microvesicles and exosomes. Differential centrifugation identified uromodulin in the supernatant, microvesicles, and exosomes of the urine of healthy participants, but only in the supernatant of samples from patients with DKD, suggesting that glycation influences uromodulin function. Finally, the diagnostic and prognostic utility of measuring urinary glcUMOD concentration was examined. Urinary glcUMOD concentration was substantially higher in DKD patients than non-diabetic CKD patients. Urinary glcUMOD concentration predicted DKD status, particularly in patients with CKD stages 1-3a aged < 65 years and with urine glcUMOD concentration ?9,000 arbitrary units (AU). Urinary uromodulin is apparently glycated in DKD and forms AGEs, and glcUMOD may serve as a biomarker for DKD. ? 2017 The Author(s).
SDGs
Other Subjects
biological marker; Tamm Horsfall glycoprotein; advanced glycation end product; biological marker; Tamm Horsfall glycoprotein; adult; aged; Article; case control study; centrifugation; chronic kidney failure; controlled study; diabetic nephropathy; disease severity; exosome; female; glycation; human; immunoprecipitation; kidney function; liquid chromatography-mass spectrometry; major clinical study; male; membrane microparticle; molecular weight; priority journal; urine level; diabetes mellitus; diabetic nephropathy; metabolism; middle aged; procedures; prognosis; receiver operating characteristic; risk assessment; severity of illness index; urine; Aged; Biomarkers; Case-Control Studies; Diabetes Mellitus; Diabetic Nephropathies; Female; Glycosylation End Products, Advanced; Humans; Male; Middle Aged; Prognosis; Risk Assessment; ROC Curve; Severity of Illness Index; Uromodulin
Type
journal article