The central aim of this study is to improve understanding of how metabolic pathways that contribute to adiposity also amplify risks of kidney disease progression and cardiovascular disease in subjects with moderate to severe CKD. In order to achieve this goal, we propose the following aims through a randomized 2x2 factorial design trial in subjects with moderate to severe CKD: (a) To assess the feasibility of implementing aerobic exercise and caloric restriction interventions, and (b) To examine the effects of aerobic exercise and caloric restriction on a metabolic risk profile, including systemic measures of oxidative stress, inflammation, insulin resistance, and endothelial dysfunction.

Hypothesis: We hypothesize that implementation of caloric restriction and aerobic exercise is feasible and can improve the metabolic milieu (as assessed by measures of oxidative stress, inflammation, insulin resistance, and endothelial dysfunction) in subjects with moderate to severe CKD.

Interim analysis may be performed (no specific plan at this time).

Inclusion Criteria:

• Stage III-IV CKD measured by the MDRD equation with eGFR 15-60 ml/min/1.73m2;
• Age 18-75 years;
• BMI ≥ 25;
• Life expectancy ≥ 1 year;
• Ability to understand and provide informed consent.

Exclusion Criteria:

• Any acute inflammatory condition (including chronic infection requiring treatment, and collagen vascular disease including active gout);
• Pregnancy;
• Taking high-dose anti-oxidants (Vitamin E or C);
• Chronic use of anti-inflammatory medication except low dose (< 10mg/d) prednisone and aspirin (< 100 mg/day);
• Significant cardiac or vascular disease (symptomatic disease or CV event including congestive heart failure within 6 months);
• Significant occlusive atherosclerotic disease or ischemic disease (on non-invasive or invasive diagnostic procedures);
• Significant physical immobility or disabilities (joint replacement, muscular disorders);
• Type I diabetes mellitus, or Type II requiring insulin therapy;
• History of poor adherence to medical regimen;
• Those subjects who have a diagnosis of atrial fibrillation or a pacemaker will be allowed in the study but will not undergo Arterial Tonometry (PWV) studies.