Resveratrol and Vascular Function in CKD

The proposed research is clinical study evaluating the therapeutic benefits of resveratrol on vascular function in patients with chronic kidney disease (CKD). The study aims to establish that resveratrol will improve endothelial function and functional performance by reducing oxidative stress and in conjunction with lowering markers of inflammation and oxidative stress.

Patients with chronic kidney disease (CKD) have an exceptionally high risk for cardiovascular disease (CVD), and are 10 times more likely to die from CVD prior to requiring dialysis or kidney transplantation. Inflammation, oxidative stress and vascular dysfunction (impaired endothelial function and increased large elastic artery stiffness), are highly prevalent in CKD and contribute to the high incidence of CVD in this patient population. In addition, patients with CKD suffer from high rates of cognitive decline for which we lack effective therapies. Thus, therapeutic interventions targeting inflammation, oxidative stress, vascular dysfunction in CKD are a priority. Wine intake, which is known to be rich in various polyphenolic compounds, might have a variety of health benefits. Among these polyphenols, the stilbene derivative resveratrol (RSV), a naturally occurring polyphenol found in grapes and red wine, has recently come to light, as it has been shown to exert potent anti-diabetic, anti-oxidative and anti-inflammatory actions. Importantly, recent studies have demonstrated that resveratrol is well-tolerated (37) and may confer similar benefits in individuals at high risk of CVD, such as improved endothelial function in individuals with metabolic syndrome (i.e. diabetes) The primary goal of this application is to determine whether 6 wks resveratrol (RSV) supplementation improves vascular function by reducing oxidative stress in a randomized, double-blind, cross-over study of 25 patients with diabetic kidney disease. The investigators hypothesize that: 1) 6 wks RSV will improve vascular function as measured via BA-FMD vs. placebo and 2) that the improvement in vascular function will be related, at least partially, to a reduction in oxidative stress.

Resveratrol, Kidney Diseases, Renal Insufficiency, Diabetes, Oxidative stress, Endothelial dysfunction

Subjects will be randomized to either receive the following intervention: placebo or resveratrol for six weeks and then after a two week washout will be assigned the alternate study drug.

Patients will receive resveratrol 400 mg PO per day in divided doses of 200 mg in the morning and 200 mg in the evening

Inclusion Criteria: CKD stage III (estimated GFR: 30-60 mL/MIN/1.73m2) Able to give informed consent Angiotensin converting enzyme inhibitor or angiotensin II receptor bloocker for > 3 month prior to the study Type II diabetes mellitus Exclusion Criteria: Consuming > 2 glasses/day red wine and/or taking resveratrol or vitamin C supplement in the past 12 months Life expectancy <1 year BMI >40 kg/m2 1 Pregnant, breastfeeding, or unwilling to use adequate birth control Uncontrolled hypertension; blood pressure > 140/90 Uncontrolled type II DM; AIC > 8.5 Currently taking anticoagulants including: coumadin, dalteparin, enoxaparin, haparin, and plavix. Severe liver disease Severe systolic heart failure Hospitalization within the last 3 months Active infection or antibiotic therapy Immunosuppressive therapy within the last year Currently partaking in another research study