Effects of Intentional Weight Loss Interventions in Chronic Kidney Disease

Obesity is an established risk factor for development and progression of kidney disease. Intentional weight loss in people without kidney disease results in an improvement in diabetes, blood pressure, cholesterol, cardiovascular disease and overall death rates. The investigators do not know whether this holds true in patients with chronic kidney disease. In the proposed pilot study, the investigators will analyze if kidney function stabilizes after weight loss interventions in obese kidney disease patients and the mechanisms that might mediate this beneficial effect. If weight loss in kidney disease patients results in stabilization of kidney function, this would provide an opportunity to conduct a long-term prospective study to analyze the sustained benefits of weight loss in kidney disease patients.

Specific aim 1:

To ascertain the effects of lifestyle modification or bariatric surgery on urinary protein excretion and renal function among obese CKD patients.

Hypothesis: Weight loss attained through either lifestyle modification or surgical intervention will result in lowering of urinary protein excretion and stabilization of renal function among obese CKD patients.

Specific aim 2:

To identify the mechanism that mediates the change in urinary protein excretion and renal function among obese CKD patients undergoing lifestyle modification or bariatric surgery.

Hypothesis: Weight loss attained through either lifestyle modification or surgical intervention will result in amelioration of endothelial dysfunction, inflammation, insulin resistance and an increase in High Molecular Weight (HMW) adiponectin levels that then mediate the improvement in urinary protein excretion and renal function among obese CKD patients.

In this non-randomized prospective study, three different groups of patients will be enrolled. Group 1 will include obese chronic kidney disease (CKD) patients undergoing lifestyle modifications, Group 2 will include obese CKD patients undergoing bariatric surgery and Group 3 will include obese CKD patients undergoing no specific weight loss interventions (control group).

The lifestyle group will undergo supervised exercise training 5 days per week and follow hypocaloric diet based on the recommendations by a dietitian for 12 weeks. The exercise training will consist of walking, running on a treadmill and stationary cycling on a cycle ergometer. Patients will undergo adipokines, markers of inflammation,insulin resistance, renal function, bioimpedance analysis,DEXA measurement at baseline, 3- and 6-month intervals. CKD patients who undergo bariatric surgery and the control group will also undergo same blood tests, renal function studies and body composition studies at baseline, 3- and 6-month intervals.

Eligibility Criteria:
Inclusion Criteria:

1. Adult (age \> 18 years) individuals with BMI \> 35 kg/m2
2. Patients with stage III CKD (eGFR 30-59 ml/min and with or without microalbuminuria or proteinuria)
3. Individuals who are eligible for bariatric surgery, based on National Institutes of Health and clinical criteria (BMI \> 40 kg/m2 BMI \> 35 kg/m2 with co-morbidities and \> 18 years of age), and do not have any health related or psychiatric contraindications for the surgery (for bariatric surgery group only)

Exclusion Criteria:

1. History of prior and functioning kidney transplant or on dialysis
2. Cardiovascular conditions including significant known coronary artery disease (recent PCI or CABG within last 6 months), uncompensated congestive heart failure and/or EF \<30%, history of stroke (within last 6 months), or uncontrolled hypertension (defined as SBP \> 180 mm Hg or DBP \> 110 mm Hg).
3. HbA1C \>8.0%
4. Hemoglobin \<10 g/dl or hematocrit \<30 (within the last 6 months)
5. Presence of active inflammatory disease such as AIDS, hepatitis B or C, or other active inflammatory diseases such as vasculitis
6. Patient being treated for malignancy (excluding basal or squamous cell carcinoma of the skin)
7. Patients taking anti-inflammatory medication such as NSAIDS except aspirin \< 325 mg/day over the past 30 days, or on any dose of prednisone therapy
8. On other study drug protocols
9. Patient on beta-blocker therapy - only for diet/exercise group
10. Patients can be on Angiotensin converting enzyme inhibitors/Angiotensin receptor blocker therapy that was started at least 3 months prior to the enrollment. New Angiotensin converting enzyme inhibitors/Angiotensin receptor blocker therapy initiation will not be allowed during the study period