Urinary glycated uromodulin in diabetic kidney disease

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) but non-DM, 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. Urinary uromodulin is...

Source: Clinical Science - June 7, 2017 Category: Biomedical Science Authors: Chang, C.-C., Chen, C.-Y., Huang, C.-H., Wu, C.-L., Wu, H.-M., Chiu, P.-F., Kor, C.-T., Chen, T.-H., Chang, G.-D., Kuo, C.-C., Wen, H.-C., Huang, C.-Y., Chang, C.-H. Tags: PublishAheadOfPrint Source Type: research