Resveratrol and Vascular Function in CKD

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.

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