Uric Acid and the Endothelium is CKD

• Systemic inflammation and oxidative stress [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Inflammation will be measured by plasma levels of the following: hs- CRP, interleukin 6 (IL-6), and monocyte chemotactic protein-1 (MCP-1). Oxidized low density lipoprotein cholesterol (oxLDL), asymmetric dimethylarginine (ADMA), and 8-isoprostanes, as markers of oxidative stress.
• Inflammation and oxidative stress in the endothelial cells [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Actual measurements: intercellular adhesion molecule (ICAM-1) and nuclear factor kappa-B (NFkappa-B p65), nitrotyrosine, Nox4-containing NAD(P)H oxidase complexes, and endothelial nitric oxide synthase (eNOS).

• Systemic inflammation and oxidative stress [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Inflammation will be measured by plasma levels of the following: hs- CRP, interleukin 6 (IL-6), and monocyte chemotactic protein-1 (MCP-1). Oxidized low density lipoprotein cholesterol (oxLDL), asymmetric dimethylarginine (ADMA), and 8-isoprostanes, as markers of oxidative stress.
• Inflammation and oxidative stress in the endothelial cells [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Actual measurements: intercellular adhesion moecule (ICAM-1) and nuclear factor kappa-B (NFkappa-B p65), nitrotyrosine, Nox4-containing NAD(P)H oxidase complexes, and endothelial nitric oxide synthase (eNOS).

This study will test the hypothesis that uric acid impairs the function of vessels in patients with kidney disease

The purpose of the study is to understand the effect of lowering serum uric acid levels on vascular function in individuals with chronic kidney disease by comparing the effects of:

1) Allopurinol therapy and 2) Placebo.

Patients will receive: 3 month study drug (either allopurinol or placebo), with assessment of serum uric acid levels and vascular function.

• Drug: Allopurinol
  Xanthine oxidase inhibitor- effective at lowering uric acid levels.
  Other Name: Zyloprim, Allohexal, Allosig, Milurit, Alloril, Progout, Zyloric.
• Other: Placebo
  Placebo tablets with no active ingredient

• Placebo Comparator: Control
  Patients who are randomized to this group will received placebo tablets. Placebo tables do not contain an active ingredient. This group will be used as a baseline group to compare the effects of lowering uric acid on vascular function.
  Intervention: Other: Placebo
• Active Comparator: Allopurinol
  Patients who are randomized to this group will receive allopurinol tablets. Allopurinol is a medicine that lowers uric acid levels. The effects of lowering uric acid on vascular function outcomes will be assessed and compared to the control group.
  Intervention: Drug: Allopurinol

Inclusion Criteria:

• Individuals with moderate chronic kidney disease (CKD stage III) with estimated glomerular filtration rates between 30-60 mL/min/ 1.73m2
• Elevated uric acid levels
• Age range: more than 18 years old
• Ability to give informed consent
• Albumin > 3.0 g/dL
• BMI < 40 kg/m2

Exclusion Criteria:

• Life expectancy < 1.0 years
• Expected to undergo living related kidney transplant in 6 months
• Pregnant, breast feeding, or unwilling to use adequate birth control
• History of severe liver disease
• History of severe congestive heart failure
• History of hospitalizations within 3 months
• Active infection, on antibiotics
• History of Warfarin Use or other medications that are contraindicated with allopurinol
• Uncontrolled hypertension
• History of acute gout on Allopurinol
• History of adverse reaction to Allopurinol
• Immunosuppressive therapy within the last 1 yr