Resveratrol reduces albuminuria in diabetic nephropathy: A randomized double-blind placebo-controlled clinical trial

Albuminuria is the most important indicator of diabetic nephropathy (DN). Resveratrol, a natural compound found in grape skins and red wine, has antioxidant effects. This study aimed to evaluate the effects of resveratrol on DN.In this randomized, double-blind, placebo-controlled clinical trial, 60 patients with type 2 diabetes and albuminuria were randomly assigned to receive either resveratrol (500mg/day) or placebo for 90 days. Losartan (12.5mg/day) was also administered to all participants. Primary outcomes were urinary albumin/creatinine ratio, estimated glomerular filtration rate (eGFR) and serum creatinine levels. Secondary outcomes were oxidative stress markers, and anthropometric and biochemical measures.Mean urine albumin/creatinine ratio was significantly reduced in the resveratrol group vs placebo (-46.4mg/g, 95% CI: -64.5 to -28.3 vs 29.9mg/g, 95% CI: 4.9 to 54.9; P<0.001), whereas eGFR (1.7mL/min/1.73m2, 95% CI: -3.4 to 6.8 vs -4.0, 95% CI: -8.2 to 0.2; P=0.08) and serum creatinine (-0.3mg/dL, 95% CI: -0.1 to 0.1 vs 0.1mg/dL, 95% CI: -0.0 to 0.1; P=0.13) were unchanged. Serum antioxidant enzymes were significantly increased with resveratrol. After adjusting for confounding variables, the effect of resveratrol in reducing urinary albumin excretion was still significant (P<0.001). Regression analysis revealed that every 1-cm decrease in waist circumference and 1-μmol/L increase in nitric oxide (NO) was associated with 9.4mg/g and 4.0mg/g reductions, respectively, of urine albumin/creatinine ratio.This clinical trial has shown that resveratrol may be an effective adjunct to angiotensin receptor blockers (ARBs) for reducing urinary albumin excretion in patients with DN (ClinicalTrials.gov: NCT02704494).