Exercise Intolerance in Renal Failure

Conditions:Renal Impairment / Chronic Kidney Disease
Therapuetic Areas:Nephrology / Urology
Age Range:18 - 75
Start Date:May 2011
Contact:Melanie Jefferson, MS

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The Role of Neurovascular Dysfunction and Oxidative Stress in the Exercise Intolerance of Renal Failure

Patients with chronic kidney disease have profound exercise intolerance which contributes to
an increased risk of cardiovascular disease. The investigators have found that chronic
kidney disease patients have an exaggerated increase in blood pressure during certain forms
of exercise that could certainly contribute to exercise dysfunction as well as
cardiovascular risk. The investigators will test the mechanisms underlying this exaggerated
blood pressure response, as well as the potential benefits of short-term tetrahydrobiopterin
(BH4) with folic acid on both exercise dysfunction and cardiovascular risk factors in
chronic kidney disease. The investigators will test whether short-term treatment with
tetrahydrobiopterin (BH4), a cofactor for nitric oxide, together with folic acid improves
inflammation, vascular health, and adrenaline levels, both at rest and during exercise in
chronic kidney disease.

Inclusion Criteria:

Patients with chronic kidney disease (Stages I, II, and III) who do not regularly
exercise, willing and able to cooperate with the protocol. CKD Stages I, II, and III will
be defined as reduction in estimated glomerular filtration rate (eGFR) to 30-59 cc/minute
as calculated by the modified MDRD equation100, or an eGFR>60 cc/minute with proteinuria
greater than 500 mg/g of Creatinine or 500 mg per 24 hours. CKD patients must have stable
renal function (no greater than a 20% reduction in eGFR over the prior 3 months).
Controls will be matched for age, gender, race, and hypertensive status.

Exclusion Criteria:

- severe CKD (eGFR<30 cc/minute)

- drug or alcohol abuse

- diabetes

- any serious systemic disease that might influence survival

- severe anemia with hgb level <10 g/dL

- clinical evidence of congestive heart failure or ejection fraction below 35%

- any history of past myocardial infarction or cerebrovascular accident

- symptomatic heart disease determined by electrocardiogram, stress test, and/or

- treatment with central alpha agonists

- uncontrolled hypertension with BP greater than 160/90 mm Hg

- low blood pressure with BP less than 110/60

- history of nephrolithiasis

- pregnancy or plans to become pregnant

- treatment with vitamin C within the past 3 months

- hepatic enzyme concentrations greater than 2 times the upper limit of normal

- HIV infection

- surgery within the past 3 months

- previous treatment with BH4

- known hypersensitivity to BH4

- any condition that places the participant at high risk of poor adherence or poor

- patients must be willing to use an acceptable method of contraception if of
childbearing age
We found this trial at
1364 Clifton Rd NE
Atlanta, Georgia 30322
(404) 712-2000
Emory University Hospital As the largest health care system in Georgia and the only health...
Atlanta, GA
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Decatur, Georgia 30033
Decatur, GA
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