Curcumin and Vascular and Cognitive Function in Patients With Chronic Kidney Disease

Patients with chronic kidney disease (CKD) are at increased risk of death from cardiovascular
disease (CVD). 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, and cognitive impairment in CKD are a biomedical priority.

Curcumin is a natural polyphenol with anti-inflammatory and antioxidant characteristics. It
is safe and widely-available. Preliminary data in old mice and healthy middle-aged (MA)/older
adult humans indicate that curcumin administration improves endothelial dysfunction and large
artery stiffness by reducing oxidative stress and inflammation. Additionally, 12 weeks of
curcumin supplementation improves episodic memory in MA/older adults.

The primary goal of this R01 application is to extend previous findings in healthy MA/older
adults to patients with CKD, a growing clinical population with extensive baseline vascular
dysfunction and cognitive impairment who presently have few treatment options. The hypothesis
is that curcumin improves vascular endothelial function and large elastic artery stiffness in
MA/older adults with stage IIIb and IV CKD (estimated GFR 15-45 mL/min/1.73m2). The possible
mechanisms by which curcumin improves vascular function will be evaluated as well as whether
curcumin improves cognitive function in these patients.

Specific aim 1a will determine if 12 months of curcumin supplementation will improve brachial
artery-flow mediated dilation (BA-FMD) (endothelial function) and aortic pulse wave velocity
(aPWV) (arterial stiffness) compared to placebo (randomized placebo-controlled double-blind
study). Specific aim 1b will evaluate whether the curcumin-induced improvements in BA-FMD and
aPWV are mediated by reduced oxidative stress, and will evaluate the effects of curcumin on
systemic and endothelial cell markers of inflammation and oxidative stress. Importantly,
specific aim 2 will evaluate the effects of curcumin supplementation on cognitive function,
an important complication of CKD, using the NIH Cognitive Toolbox Battery.

Inclusion Criteria:

- CKD stage IIIB and IV

- BMI<35 kg/m2

- Able to give informed consent

Exclusion Criteria:

- Consuming a diet rich in curcumin or taking curcumin supplements in the past 12 months

- Life expectancy <1 year

- Pregnant, breastfeeding, or unwilling to use adequate birth control

- Uncontrolled hypertension

- Severe liver disease

- Severe congestive heart failure

- Hospitalization within the last 3 months

- Active infection or antibiotic therapy

- Immunosuppressive therapy within the last year