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(P0.01).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(P0.01),and UACR and HbA1c were independent determinants for exosome-DPP4(P0.01).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.