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 (500 mg/day) or placebo for 90 days. Losartan (12.5 mg/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 (−46.4 mg/g, 95% CI: −64.5 to −28.3 vs 29.9 mg/g, 95% CI: 4.9 to 54.9; P < 0.001), whereas eGFR (1.7 mL/min/1.73 m2, 95% CI: −3.4 to 6.8 vs −4.0, 95% CI: −8.2 to 0.2; P = 0.08) and serum creatinine (−0.3 mg/dL, 95% CI: −0.1 to 0.1 vs 0.1 mg/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 9.4 mg/g and 4.0 mg/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).