Effects of Mesna on Homocysteine in Kidney Failure
Condition: End Stage Renal Disease
MeSH terms: Kidney Diseases; Kidney Failure, Chronic
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this research study is to examine the effect of a drug called mesna on the
      removal of homocysteine from blood during dialysis. Homocysteine is an amino acid (protein
      building block) found in the blood of all people, however it is considerably elevated in
      dialysis patients. People with increased levels of homocysteine in their blood are at
      increased risk of developing plaque buildup in their arteries and other related problems such
      as heart attack and stroke. This study will determine if mesna can improve the rate of
      homocysteine removal from blood during dialysis.
    

Detailed description: 
      Homocysteine is a thiol amino acid derived from dietary methionine. Elevated plasma total
      homocysteine (tHcy), termed hyperhomocysteinemia, is a graded, independent risk factor for
      the development of atherosclerosis. Elevated plasma tHcy can be normalized by supplementation
      with folic acid and vitamins B6 and B12 in most patients with normal renal function and this
      treatment has been shown to halt the progression of atherosclerotic plaque.

      Over 90% of patients with end-stage renal disease (ESRD) requiring hemodialysis have elevated
      plasma tHcy. The leading causes of morbidity and mortality in these patients are
      cardiovascular-related pathologies such as myocardial infarction and stroke. Vitamin
      supplementation consistently fails to normalize elevated plasma tHcy in patients with ESRD,
      thus leaving them at increased risk. Plasma tHcy is 70 - 80% covalently protein bound
      limiting the effectiveness of dialysis as a tHcy lowering treatment.

      Mesna (sodium 2-mercaptoethanesulfonic acid) is a thiol-containing drug currently indicated
      to prevent hemorrhagic cystitis associated with ifosfamide chemotherapy. Mesna has
      incidentally been shown to deplete plasma thiols in cancer patients undergoing ifosfamide
      chemotherapy. Mesna acts to exchange with thiols bound to plasma proteins enhancing their
      renal excretion. In vitro studies in our laboratory have shown that mesna rapidly (within 5
      minutes) exchanges with protein bound homocysteine yielding a significantly larger dialyzable
      fraction of the thiol amino acid.

      A pilot study recently completed by our group demonstrated a significant decrease in tHcy in
      eight hemodialysis patients receiving 12 mg/kg mesna three times a week pre-dialysis for one
      week. Although this therapy did cause a significant decline in tHcy, mesna failed to reduce
      tHcy to normal levels. The cumulative effects of mesna administration over a longer treatment
      period should be evaluated.
    

Intervention name(s): Mesna; Saline
Intervention type(s): Drug; Other
Intervention description(s): 12 mg/kg IV infusion over five minutes at the beginning of dialysis thrice weekly.; Saline IV infusion over five minutes at the beginning of dialysis thrice weekly.
Other intervention name(s): Mesnex; Uromitexan
Intervention MeSH terms: Mesna
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: homocysteine; hemodialysis; mesna