Research Updates in Kidney and Urologic Health

NIDDK Launches Trial To Reduce CVD in Kidney Patients

The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) study is under way. This nationwide, multicenter clinical trial will determine whether total homocysteine-lowering treatment with a high-dose combination of folic acid, vitamin B12, and vitamin B6 reduces the rate of cardiovascular disease outcomes among stable renal transplant recipients with mild to moderately elevated total homocysteine levels. A total of 4,000 renal transplant recipients will be recruited over 2 years, beginning in the winter of 2002.

Twenty major renal transplant centers in the United States and Canada will conduct this trial, which is designed to increase knowledge about elevated homocysteine levels as a risk factor for cardiovascular disease in patients with chronic renal insufficiency. It is well known that patients with chronic renal disease are at high risk for cardiovascular disease. Some of this elevated risk is due to a higher prevalence of established arteriosclerotic risk factors such as advanced age, hypertension, dyslipidemia, diabetes, and physical inactivity, but unique renal insufficiency/uremia-related risk factors may also exist. Prominent among these unique risk factors in the chronic renal disease population are elevated levels of homocysteine.

For several reasons, renal transplant recipients are a unique subpopulation for testing the hypothesis that lowering total homocysteine levels may reduce the risk of cardiovascular disease events in the overall chronic renal disease population.

• They exhibit a high rate of new and recurrent cardiovascular disease outcomes.
  
  
• They display an excess prevalence of hyperhomocysteinemia despite the nationwide fortification of cereal grain flour, which is credited with reducing homocysteine levels in the general population.
  
  
• Their total homocysteine levels can be safely and successfully normalized with folic acid, vitamin B12, and vitamin B6.
  
  

The overall conditions in the renal transplant population—renal impairment, mild to moderate hyperhomocysteinemia that can be normalized with B-vitamin supplements, and excess cardiovascular disease outcomes—are representative of the estimated 11 million patients with chronic renal insufficiency (serum creatinine of 1.5 mg/dL or higher) who have not yet reached end-stage renal disease.

The clinical trial will be double masked. Participants will be randomized to either a multivitamin containing high doses of folic acid and vitamins B6 and B12 or one with no folic acid and the estimated average daily requirements of vitamins B6 and B12. The primary outcome of the trial is recurrent or de novo arteriosclerotic cardiovascular disease, defined as nonfatal or fatal coronary heart, cerebrovascular, and peripheral vascular disease events: myocardial infarction, resuscitated sudden death, coronary artery revascularization, stroke, and peripheral or renovascular disease that requires an invasive procedure such as angioplasty, stenting, endarectomy, aneurysm repair, or lower extremity amputation for an arteriosclerotic complication.

The clinical trial is being conducted under a cooperative agreement. Andrew G. Bostom, M.D., M.S., will direct the clinical coordinating center at Rhode Island Hospital. Lloyd Chambless, Ph.D., will serve as principal investigator at the data coordinating center at the University of North Carolina.

[Top]