Submitted to: Transplantation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/28/2001
Publication Date: 2/1/2002
Citation: FRIEDMAN, A.N., ROSENBERG, I.H., SELHUB, J., LEVEY, A.S., BOSTOM, A. HYPERHOMOCYSTEINEMIA IN RENAL TRANSPLANT PATIENTS. TRANSPLANTATION 2002;2:308-313. Interpretive Summary: Homocysteine is an amino acid which is formed in the body from another amino acid, methionine after the latter is used for other functions called methylations. Homocysteine serves in the body to reform methionine but can also be potentially harmful if its concentration in the blood is increased. High blood homocysteine is thought to increase the risk of cardiovascular disease. High homocysteine occurs because of vitamin deficiency, genetic defects or kidney disease. People on kidney dialysis have high homocysteine that cannot be lowered by vitamin supplementation no matter how much vitamins are taken. People with kidney transplant have slightly lower homocysteine than those on kidney dialysis. The homocysteine in kidney transplant patients can be lowered by doses of vitamins that are considerably higher than those needed by normal persons. We speculated that the high homocysteine in patients with kidney disease before dialysis can also be lowered by high vitamin doses.
Technical Abstract: Renal transplantation is a commonly performed curative procedure for end-stage renal disease. With the increase in renal allograft half-lives, attention is now being focused on cardiovascular morbidity and death in the renal transplant recipient (RTR) population. Among the more novel cardiovascular disease (CVD) risk factors for which this group is at risk is hyperhomocysteinemia. Hyperhomocysteinemia has been associated with an increased risk of CVD, although prospective randomized trials designed to prove causality are still ongoing. Since plasma total homocysteine levels are inversely related to renal function, RTRs have a greatly increased prevalence of hyperhomocysteinemia. Other determinants of homocysteine include B-vitamins, albumin, age, and genetic polymorphisms. Although RTRs are resistant to the typical B-vitamin doses used to correct hyperhomocysteinemia in the general population, they do respond to supraphysiologic dose therapy. In terms of prevalence, etiology, and treatment of hyperhomocysteinemia, RTRs are very similar to the much larger chronic renal insufficiency population. For this reason, RTRs have been chosen as an ideal study population in investigating the effect of reducing hyperhomocysteinemia on CVD outcomes.