Sympatholysis in Chronic Kidney Disease

Functional Sympatholysis and Exercise Intolerance in Chronic Kidney Disease

The purpose of this study is to find out why patients with chronic kidney disease (CKD) have poor exercise capacity and what causes an increase in blood pressure during exercise (i.e. increased adrenaline levels, or decreased ability of blood vessels to dilate).

Patients with chronic kidney disease (CKD) suffer from exercise intolerance and poor physical capacity which contributes to increased cardiovascular risk in this patient population. Prior studies have shown that CKD patients have an exaggerated increase in blood pressure (BP) during both static and rhythmic exercise. Such abnormal hemodynamic responses to exercise can contribute to poor physical capacity and abnormal muscle blood flow during exercise in these patients. The goals of this project are to investigate the mechanisms and potential therapies targeting the abnormal hemodynamic response during exercise in CKD by examining the roles of impaired vasodilation, and exaggerated vasoconstriction.

Inclusion Criteria:

• Veterans with Stages III and IV Chronic Kidney Disease (CKD)
• Kidney transplant recipients with varying degrees of kidney function
• Veterans 18-75 years old, without kidney disease, as study controls
• Exercise less than 20 minutes twice per week
• Willing and able to cooperate with the protocol

Exclusion Criteria:

• Severe CKD (estimated glomerular filtration rate (eGFR) < 15 cc/minute)
• Metabolic alkalosis (serum bicarbonate > 28 meq/L)
• Ongoing drug or alcohol abuse
• Diabetic neuropathy
• Any serious systemic disease that might influence survival
• Severe anemia with hemoglobin (Hbg) level < 10 g/dL
• Clinical evidence of congestive heart failure or ejection fraction below 35%
• Symptomatic heart disease determined by prior electrocardiogram, stress test, and/or history
• Treatment with central alpha agonists (clonidine)
• Uncontrolled hypertension with blood pressure (BP) greater than 170/100 mmHg
• Low blood pressure with BP less than 100/50 mmHg
• Pregnancy or plans to become pregnant
• Current treatment with monoamine oxidase inhibitors (MAOIs)
• Inability to exercise on a stationary bicycle