Effects of valsartan combined with α-lipoic acid on renal function in patients with diabetic nephropathy: a systematic review and meta-analysis

BACKGROUND: Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes, valsartan and α-lipoic acid alone or in combination has been used for the treatment of patients with DN. However, some results in these clinical reports were still controversial. The purpose of this study was to evaluate the efficacy of valsartan combined with α-lipoic acid on renal function in patients with DN. METHODS: We searched the electronic databases including PubMed, Sciencedirect, EMBASE, Cochrane library, Chinese national knowledge infrastructure (CNKI) and Wanfang databases, and the publication deadline was limited to January 2020. Randomized controlled trials (RCTs) evaluating the effects of valsartan combined with α-lipoic acid in DN patients were included. Pooled estimates were conducted using a fixed or random effect model. The outcomes included urinary albumin excretion rate (UAER), and the level of urinary albumin, β(2)-microglobulin (β(2)-MG), hypersensitive C-reactive protein (hs-CRP) and oxidative stress. RESULTS: 11 studies with 1294 participants were included in this study. The pooled analysis indicated that α-lipoic acid combined with valsartan could remarkably reduce UAER (P < 0.00001, SMD = -1.95, 95%CI = -2.55 to − 1.20; P = 0.03, SMD = -0.85, 95%CI = -1.59 to − 0.1) and the level of urinary albumin (P = 0.001, SMD = -1.48, 95%CI = − 2.38 to − 0.58; P = 0.01, SMD = -1.67, 95%CI = -3.00 to − 0.33), β(2)-MG (P < 0.001,SMD = − 2.59, 95%CI = -3.78 to − 1.40; P = 0.03, SMD = -0.48, 95%CI = -0.93 to − 0.04) when compared with valsartan or lipoic acid monotherapy in patients with DN. However, there was no significant difference in the level of hs-CRP among the three therapies (P = 0.06, SMD = -2.80, 95%CI = -5.67 to 0.07; P = 0.10, SMD = -0.42, 95%CI = − 0.92 to 0.08). In addition, α-lipoic acid combined with valsartan markedly increased the level of SOD (P = 0.03, SMD = 1.24, 95%CI = 0.32 to 1.03; P = 0.0002, SMD = 0.68, 95%CI = 0.32 to 1.03) and T-AOC (P < 0.00001, SMD = 0.89, 95%CI = 0.62 to 1.16; P = 0.02, SMD = 0.58, 95%CI = 0.10 to1.07), and reduced the level of MDA(P = 0.0002, SMD = -1.99, 95%CI = -3.02 to − 0.96; P = 0.0001, SMD = -0.69, 95%CI = -1.04 to − 0.34). CONCLUSIONS: α-lipoic acid combined with valsartan could significantly reduce the level of urinary albumin and oxidative stress, increase antioxidant capacity and alleviate renal function damage in patients with DN, and this will provide a reference for the selection of treatment drugs for DN.