Changes of urinary exosomal leucine aminopeptidase and dipeptidyl peptidase 4 in diabetic nephropathy

AIM: To investigate the changes of urinary exosomal enzymes and the correlation with diabetic nephropathy.METHODS: Thirty-four healthy volunteers and 127 patients of type 2 diabetes mellitus (T2DM) were included in the study. The healthy volunteers served as control. The patients with T2DM were divided into 3 groups based on their 24 h urinary albumin/creatinine ratio (UACR): 50 patients with microalbuminuria in early DN group (DN1), 34 patients with macroalbuminuria in overt DN group (DN2) and 43 patients without albuminuria in DM group. The levels of urine exosomal leucine aminopeptidase(exosome-LAP) and exosomal dipeptidyl peptidase 4(exosome-DPP4) were determined by enzyme-linked immunosorbent assay (ELISA). The following methods were used to determine the biochemical parameters: liquid chromatography for glycated hemoglobin (HbA1c), chemical modification method for cholesterol (CH), Jaffe-kinetic assay for creatinine (CR) and urease-GLDH method for blood urea nitrogen (BUN). Multiple stepwise linear regressions were used to analyze the relationship of exosome-LAP or exosome-DPP4 with HbA1c, CH, UACR, CR and BUN. RESULTS: The levels of exosome-LAP and exosome-DPP4 in DM, DN1 and DN2 groups were significantly higher than those in control group (P<0.01). The exosome-LAP in DN2 group was significantly higher than that in DM group. Correlation analysis showed that the levels of urinary exosome-LAP and exosome-DPP4 were positively correlated with HbA1c, CH, UACR, CR and BUN. Multiple stepwise linear regression analysis showed that CH and UACR were independent determinants for exosome-LAP (P<0.01), and UACR and HbA1c were independent determinants for exosome-DPP4 (P<0.01). CONCLUSION: Urine exosome-LAP and exosome-DPP4 are correlated with the severity of diabetic nephropathy. These parameters may serve as clinical markers for the diagnosis and prognosis evaluation of diabetic nephropathy.