Mitochondria and Chronic Kidney Disease
Condition: Hemodialysis-Induced Symptom; Mitochondrial Diseases
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Mitochondrial Diseases
Intervention: Icatibant; Placebo
Intervention description: Subjects will receive either Icatibant or placebo in the first study day. After a washout period of 3 weeks, participant will receive the other treatment. Icatibant (50µg/kg/h) or placebo will be infused for 1 hour prior to the initiation of dialysis and continue through hemodialysis. Hemodialysis session will last approximately 4 hours. Two hours after the end of hemodialysis, The investigators will evaluate mitochondrial function by 31 phosphorus magnetic resonance spectroscopy.; Subjects will receive either Icatibant or placebo in the first study day. After a washout period of 3 weeks, participant will receive the other treatment. Icatibant (50µg/kg/h) or placebo will be infused for 1 hour prior to the initiation of dialysis and continue through hemodialysis. Hemodialysis session will last approximately 4 hours. Two hours after the end of hemodialysis, the investigators will evaluate mitochondrial function by 31 phosphorus magnetic resonance spectroscopy.
Intervention MeSH terms: Icatibant
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 78 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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