Urinary exosomes as a novel biomarker for evaluation of α-lipoic acid's protective effect in early diabetic nephropathy.

Abstract

Long-term administration of α-lipoic acid (α-LA) is proved to ameliorate renal impairment. Herein we assessed serum, urinary biomarkers and vascular endothelium function to evaluate its short-period therapeutic effect and identify novel biomarkers for diabetic nephropathy (DN). Sixty-two microalbuminuria-stage DN patients were randomly divided into two groups and received the following treatment for 8weeks: (1) routine treatment(DM group); (2) routine treatment with 600mg/d α-lipoic acid intravenously (α-LA group). Another total of 21 patients were recruited for the second-stage study and randomly divided into two groups: normoalbuminuria (UAER <30mg/24h) and microalbuminuria (UAER from 30-300mg/24h). With α-LA treatment, urinary albumin excretion rates (UAER), serum creatinine (SCr) and malonaldehyde (MDA) declined significantly, whereas plasma superoxide dismutase (SOD)activity increased and endothelium-dependent flow mediated vasodilation (FMD) flexibility improved dramatically. Furthermore, the improvement of FMD showed positive correlation with the variation in MDA and SOD as well (r values are .516 and .435, P<.01 and P<.05, respectively). In contrast, these markers have no significant difference in the DM group with routine treatment. Notably, the CD63 expressing of exosomes in urine was found higher in the normoalbuminuria patients compared with those in microalbuminuria, parallelly only declined markedly after α-LA administration in normoalbuminuria patients. In summary, we emphasize short-term α-LA could protect the kidney in the early DN against general oxidative stress, particularly the urinary CD63-positive exosome could be a potential sensitive and therapeutic indicator.