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

Inclusion 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

Exclusion criteria

• 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