Treatment of mild hyperhomocysteinemia in renal transplant recipients versus hemodialysis patients.

Abstract

Mild hyperhomocysteinemia is common among maintenance hemodialysis (HD) patients and renal transplant recipients (RTR) and may contribute to the excess incidence of arteriosclerotic outcomes experienced by both patient groups. Relative to their RTR counterparts, the hyperhomocysteinemia of HD patients seems to be considerably more refractory to treatment with high-dose folic acid (FA)-based B-vitamin supplementation regimens, although controlled comparison data are lacking. We compared the relative responsiveness of (n=10) RTR and (n=39) HD patients with equivalent baseline total homocysteine (tHcy) levels (i.e., RTR range=14.2-23.6 micromol/L; HD range=14.4-24.9 micromol/L) to 12 weeks of tHcy-lowering treatment. The RTR received 2.4 mg/day of FA, 50.0 mg/day of vitamin B6, and 0.4 mg/day of vitamin B12, while the HD patients received 15 mg/day of FA or an equimolar amount (17 mg/day) of the reduced folate, L-5-methyltetrahydrofolate, in addition to 50.0 mg/day of vitamin B6, and 1.0 mg/day of vitamin B12. The mean percent (%) reductions (+/-95% confidence interval) in tHcy were: RTR=28.1% (16.2-40.0%); HD=12.1% (6.6-17.7%), P=0.027 for comparison of between-groups differences by analysis of covariance adjusted for baseline tHcy levels. Moreover, (50.0%) of 10 of the RTR versus only (5.1%) of 39 of the HD patients had final on-treatment tHcy levels <12 micromol/L; P=0.002 for comparison of between-groups differences by Fisher's exact test. Relative to RTR with comparable baseline tHcy levels, the mild hyperhomocysteinemia of maintenance HD patients is much more refractory to tHcy-lowering B-vitamin treatment regimens featuring supraphysiological amounts of FA or the reduced folate, L-5-methyltetrahydrofolate. Accordingly, RTR are a preferable target population for controlled clinical trials testing the hypothesis that tHcy-lowering B-vitamin intervention may reduce arteriosclerotic cardiovascular disease event rates in patients with chronic renal disease.