Abstract
This study was designed to investigate the changes of urinary microvesicle-bound uromodulin and total urinary uromodulin levels in human urine and the correlations with the severity of diabetic kidney disease (DKD). 31 healthy subjects without diabetes and 100 patients with type 2 diabetes mellitus (T2DM) were included in this study. The patients with T2DM were divided into three groups based on the urinary albumin/creatinine ratio (UACR): normoalbuminuria group (DM, n = 46); microalbuminuria group (DN1, n = 32); and macroalbuminuria group (DN2, n = 22). We use a specific monoclonal antibody AD-1 to capture the urinary microvesicles. Urinary microvesicle-bound uromodulin and total urinary uromodulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that the levels of urinary microvesicle-bound uromodulin in DN1 and DN2 groups were significantly higher than those in control group and DM group (P < 0.01). Multiple stepwise linear regression analysis showed that UACR was independent determinant for urinary microvesicle-bound uromodulin (P < 0.05) but not for total urinary uromodulin. These findings suggest that the levels of urinary microvesicle-bound uromodulin are associated with the severity of DKD. The uromodulin in urinary microvesicles may be a specific marker of DKD and potentially may be used to predict the onset and/or monitor the progression of DKD.
Highlights
Diabetic kidney disease (DKD) is a major complication of diabetes mellitus and the most frequent cause of end-stage renal disease (ESRD) [1, 2]
We have developed an enzyme-linked immunosorbent assay (ELISA) method for urinary microvesicles-bound uromodulin using a specific monoclonal antibody, AD-1, developed by Deng et al [19, 20]
The patients with type 2 diabetes mellitus (T2DM) were divided into three groups based on the urinary albumin/creatinine ratio (UACR): normoalbuminuria group (DM, n = 46, ACR < 30 mg/g creatinine); microalbuminuria group (DN1, n = 32, ACR from 30–300 mg/g creatinine); and macroalbuminuria group (DN2, n = 22, ACR > 300 mg/g creatinine)
Summary
Diabetic kidney disease (DKD) is a major complication of diabetes mellitus and the most frequent cause of end-stage renal disease (ESRD) [1, 2]. Uromodulin is a GPIanchored glycoprotein and produced by the thick ascending limb of the loop of Henle of the mammalian kidney. It is present in large aggregates of up to several million Da in urine physiologically [5], and the monomeric molecule has a molecular weight of about 85 kDa. Uromodulin excretion in urine follows proteolytic cleavage of the ectodomain of its glycophosphatidy linositol-anchored counterpart that is situated on the luminal cell surface of the loop of Henle. Uromodulin was considered useful as a marker of renal disease [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
