Pomegranate and Hemodialysis Pilot Trial

There are currently more than 400,000 patients receiving chronic dialysis therapy in the
United States. Cardiovascular and infectious diseases are the leading causes of death in
hemodialysis patients, accounting for over 50% of all-cause mortality.

There is a complex interaction of inflammation, oxidative stress, and endothelial
dysfunction in contributing to cardiovascular and infectious risk in dialysis patients.
Since there is much evidence that an increase in oxidative stress contributes to risk of
disease in dialysis patients, it is logical to hypothesize the antioxidant therapy may be
beneficial in reducing these risks.

In addition to vitamins C and E, the most common and active antioxidant compounds that occur
naturally in foods are flavonoids. Dietary flavonoids are highly bioavailable, and have been
shown to confer antioxidant protection, inhibit platelet activation, exert vasorelaxant
effects, and reduce inflammation in human studies. In animal model studies, dietary
flavonoids have been shown to reduce the development of atherosclerosis. Polyphenols also
have potent antibacterial, antifungal, and antiviral activities.

Pomegranate juice is a rich source of potent phenolic antioxidants, which have been
demonstrated to have anti-atherogenic and vasorelaxant properties. Pomegranate derived
polyphenols have also been demonstrated to inhibit platelet activation.

Although available data are limited, several studies suggest that dietary phenols may have
beneficial effects in patients undergoing dialysis treatment. These include improvements in
lipoprotein profiles, reductions in circulating inflammatory and oxidative stress
biomarkers, reductions in infectious complications, and improvements in inflammatory
biomarkers. These observations, though limited, suggest that polyphenol based
supplementation strategies may be effective in reducing complications in those undergoing
dialysis treatment.

In this study, the investigators will administer pomegranate juice and/or fruit extract as a
targeted antioxidant therapy. The investigators will examine whether these pomegranate
products will be safe and well-tolerated. The investigators will also examine whether these
products may lead to improvements in biomarkers of oxidative stress status, inflammatory
status, and endothelial dysfunction in hemodialysis patients.

Inclusion Criteria:

- Patients with end-stage renal disease receiving thrice weekly hemodialysis

- Age > 18 or < 85 years

- Life expectancy greater than one year

- Ability to understand and provide informed consent for participation in the study

Exclusion Criteria:

- History of poor adherence to hemodialysis or medical regimen

- Prisoners, patients with significant mental illness, and other vulnerable populations

- AIDS (HIV seropositivity is not an exclusion criteria)

- Active malignancy excluding basal cell carcinoma of the skin

- Gastrointestinal dysfunction requiring parenteral nutrition

- History of functional kidney transplant < 6 months prior to study entry

- Anticipated live donor kidney transplant

- Patients taking vitamin E supplements > 60 IU/day, vitamin C > 150 mg/day or other
antioxidant or nutritional supplements

- Incident hemodialysis patients (defined as within 30 days of dialysis initiation)

- Patients hospitalized for more than 5 days within the past 30 days.

- Patients with a history of a major atherosclerotic event (defined as combined
incidence of myocardial infarction, urgent target-vessel revascularization, coronary
bypass surgery, and stroke) within three months

- Pregnancy