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

Abstract

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, β2-microglobulin (β2-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), β2-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.

Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy

“…Apart from the gut microbiota composition, the functions of the gut microbiota obviously vary in patients with T2DM and DN. Lipoic acid can reduce the level of urinary albumin and oxidative stress in patients with DN, improve antioxidant capacity, and protect kidney function ( 50 ). We have found elevated lipoic acid in DN patients, which suggests that the gut microbiota may affect drug metabolism as demonstrated in a previous study ( 51 ).…”

The Effect of α-lipoic Acid on C-Reactive Protein Level: A Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Studies

“…Even more, our subgroup analysis showed that 12 weeks (median) or shorter ALA supplementation significantly reduce CRP levels. On the other hand, results from a previously conducted meta-analysis by Saboori et al 32 showed that ALA supplementation caused significant CRP reduction when trial duration was more than 8 weeks (median), while subgroup analysis from Haghighatdoost and Hariri 33 study showed no significant CRP reduction when study duration was 9 weeks or longer (median). The observed differences between ours and other published meta-analyses regarding the duration-dependent effect of ALA on CRP levels should be attributed to the difference in the studies involved in the analysis.…”

“…The conducted meta-analysis revealed the influence that ALA has on lipid profile, male infertility, weight loss, glycemic control, and renal function in patients with diabetic nephropathy. 30 - 33 …”

“…It is important to point out that some of the included studies in the second meta-analysis have not used a placebo as a comparator. 33 It could also be noted that some of the included studies used ALA in combination with other supplements or drugs. 33 It is interesting that after comparing these two meta-analyses it could be seen that although performed in the same period only 6 studies overlapped in both meta-analyses.…”

“… 33 It could also be noted that some of the included studies used ALA in combination with other supplements or drugs. 33 It is interesting that after comparing these two meta-analyses it could be seen that although performed in the same period only 6 studies overlapped in both meta-analyses. Nevertheless, the result of both meta-analyses indicates that ALA supplementation decreases CRP levels.…”