Neurovascular Regulation During Exercise in Humans With Chronic Kidney Disease: Sympatholysis in CKD

Eligibility Criteria

• * patients with CKD (Stages III and IV), kidney transplant recipients with varying degrees of kidney function, or persons without kidney disease as matched study controls
• * sedentary and do not regularly exercise (defined as exercising \< 20 minutes twice per week)
• * CKD patients must have stable renal function (no greater than a decline of estimated glomerular filtration (eGFR) of 1 cc/min/1.73 m2 per month over the prior 6 months) and baseline serum bicarbonate 22-24 mmol/L
• * comorbid hypertension
• * severe CKD (eGFR\<15 cc/min)
• * metabolic alkalosis
• * current treatment with bicarbonate
• * ongoing drug or alcohol abuse
• * diabetic neuropathy, autonomic dysfunction
• * any serious disease that might influence survival
• * anemia with hemoglobin \<10 g/dL
• * clinical evidence of heart failure
• * volume overload or ejection fraction below 45%
• * symptomatic heart disease by EKG, stress test, and/or history
• * treatment with central α-agonists (clonidine)
• * myocardial infarction or cerebrovascular accident within the past six months
• * uncontrolled hypertension (BP\>170/100 mm Hg)
• * low BP\<100/50 mm Hg
• * surgery within the past 3 months
• * pregnancy or plans to become pregnant
• * inability to exercise on a stationary bicycle
• * contraindication to temporary withdrawal of α- and β-blockers
• * peripheral arterial disease
• * class 3 obesity (BMI\>40)
• * hypo- or hyperkalemia (K\<3.5meq/L, K\>5.0 meq/L)
• * current use of immunosuppressive medications (including but not limited to steroids, cyclophosphamide, calcineurin inhibitors, mycophenolate, biologics, methotrexate, etc)
• * arteriovenous (AV) fistula/graft
• * any contraindication to MR scanning including cardiac pacemaker, cochlear implants, neurostimulators, implanted devices with metal, any metal in the body that could pose a hazard during scanning, history of claustrophobia