Mitochondria and Chronic Kidney Disease

Mitochondrial Dysfunction in Chronic Kidney Disease

The overarching goal of this study is to determine the role of chronic kidney disease and the activation of the kallikrein-kinin system during hemodialysis on the development of mitochondrial dysfunction; the investigators will measure mitochondrial function using the gold standard method, 31-phosphorus magnetic resonance spectroscopy.

The investigators will test the hypothesis that endogenous bradykinin promotes mitochondrial dysfunction in patients undergoing hemodialysis. The investigators will first perform a randomized, placebo-controlled, double-blind, cross-over study measuring the effect of Icatibant (HOE-140), a bradykinin B2 receptor blocker, on mitochondrial function.

Inclusion Criteria:

• Adult patients who have been on maintenance hemodialysis for at least 6 months

Exclusion Criteria:

• History of functional transplant less than 6 months prior to study
• Use of immunosuppressive drugs within 1 month prior to study
• History of active connective tissue disease
• History of acute infectious disease within one month prior to study
• AIDS (HIV seropositivity is not an exclusion criteria)
• History of myocardial infarction or cerebrovascular event within 3 months
• Advanced liver disease
• Gastrointestinal dysfunction requiring parental nutrition
• Active malignancy excluding basal cell carcinoma of the skin
• Ejection fraction less than 30%
• Anticipated live donor kidney transplant
• Pregnancy, breast-feeding or child-bearing potential
• History of poor adherence to hemodialysis or medical regimen
• Subjects with cardiac pacemaker, artificial heart valve, any metallic implant, permanent tattoo, or any retained foreign metallic bodies that are contraindicated in magnetic resonance imaging.
• Inability to provide consent