Effects of Pomegranate Supplementation on Physical Function and Cardiovascular Disease Risk in Chronic Kidney Disease Patients

Chronic kidney disease (CKD) patients have very low physical function and high rates of
cardiovascular disease (CVD) mortality. The objective of the proposed research is to
evaluate the effects of dietary supplementation with a pomegranate extract, that contains
high amounts of antioxidants, on physical function and CVD risk. Patients with moderate to
severe chronic kidney disease that are NOT yet on dialysis tend to have significantly
reduced risk factors for cardiovascular disease (and other disorders) compared to dialysis
patients. This includes significantly reduced systemic markers of oxidative stress and
inflammation. As a result, therapies designed to reduce the risk of CKD co-morbidities may
differ significantly in dialysis and pre-dialysis patients. For example, dialysis patients
are recommended to INCREASE their intake of dietary protein, while pre-dialysis patients are
recommended to DECREASE their protein intake, due to differences in the pathophysiology of
the two conditions. The investigators have decided to recruit pre-dialysis patients in
addition to dialysis patients in this study because the investigators believe this will help
us determine if the efficacy of pomegranate differs between patients with different stages
of CKD.

CKD patients will be recruited under 2 phases: CKD patients not receiving dialysis treatment
(pre-dialysis patients) will be recruited in the first phase. This will include patients
with CKD stage 3-5 that are not yet on dialysis. In the second phase, only CKD patients on
dialysis treatment will be recruited. To address these questions, CKD patients will be
randomized to the following groups for 12 months: 1) no POM supplementation/control (CON),
and 2) oral supplementation with purified pomegranate extract (POM). Patients in the POM
group will ingest a 1000 milligram capsule of POM extract, 7 days per week. Patients in the
CON group will receive a placebo capsule using the same protocol.

On three occasions, at baseline, 6, and 12 months, each subject will have blood collected to
measure plasma markers of oxidative stress (TBARS, lipid peroxides), blood lipid levels, and
glucose and insulin levels. Arterial and cardiac structure and function will be measured by
vascular ultrasound and echocardiogram, respectively. A 24-hour dietary recall will be used
to assess the intake of nutrients. Leg strength will be measured on a resistance exercise
machine. Bone density and body composition will be evaluated using dual energy x-ray
absorptiometry (DXA). Pre-dialysis subjects will undergo a maximal exercise test to assess
their cardiorespiratory fitness level. In dialysis patients, instead of a maximal exercise
test, physical function will be measured by a 6-item functional fitness assessment and a
10-meter walk test.