Effect of Folic Acid Therapy on Serum Homocysteine Level in Renal Transplant Recipients S. Savaj, S. Rezakhani, F. Porooshani, and A.J. Ghods C ARDIOVASCULAR DISEASES are the leading cause of mortality and morbidity in renal transplant recipients. The high rate of cardiovascular diseases has been explained by increased prevalence of cardiovascular risk factors among renal transplant recipients. Recent stud- ies have shown that hyperhomocysteinemia is an indepen- dent risk factor of cardiovascular diseases. The prevalence of hyperhomocysteinemia increases from 5% in the general population to 70% to 100% in end-stage renal disease patients. 1 After renal transplantation in spite of good allograft function, there is only a 33% decrease in plasma homocysteine levels. 2 Our study was carried out to evaluate the effect of folate therapy on serum homocysteine levels in renal transplant recipients. PATIENTS AND METHODS The study population consisted of 17 renal transplant recipients (11 males and 6 females), mean age 38.23  9.6 years with good allograft function (serum creatinine, 1.43  0.42 mg/dL). All patients had serum homocysteine levels 15 mol/L and the posttransplantation period was 1 year (mean, 79.3  34.5 months). Patients received 5 mg/d of folic acid. After 3 months, fasting levels of homocysteine and creatinine were evaluated. Serum homocysteine was measured by ELISA method (Axis Kit). RESULTS Nine of 17 patients (52%) had normal serum homocysteine levels after 3 months of folate therapy. Folic acid therapy resulted in a 21.6% reduction in mean fasting serum homocysteine level in renal transplant recipients (23.4  7.3 vs 18.41  7.87 mol/L, P  .025). There were no signifi- cant differences in the patients’ serum creatinine levels before and after folic acid treatment. DISCUSSION AND CONCLUSION The prevalence of fasting and post–methionine-loading hyperhomocysteinemia in stable renal transplant recipients is 50% to 60%. 3 For each micromolar increase in total homocysteine level, the occurrence of cardiovascular dis- eases complications increased by 6% in these patients. 4 Short-term, placebo-controlled studies have demonstrated the safety and efficacy of folate-based B-vitamin supple- mentation for lowering fasting or nonfasting total homocys- teine levels in patients with normal renal function. 5 In patients with renal disease, supraphysiologic dose of folic acid is more effective to reduce serum homocysteine levels. Although kidney transplant recipients have better response to high-dose folate therapy in comparison to hemodialysis patients, 6 a controlled study showed folic acid therapy (5 mg/d) and vitamin B 12 therapy (0.4 mg/d) cause 26.2% reduction in fasting homocysteine level in renal transplant recipients. Vitamin B 6 (50 mg/d) decreased the post– methionine-loading serum homocysteine level by 22%. 7 We also found a 21.6% reduction in fasting serum homocys- teine level after 5 mg of folate therapy. Nine of 17 patients had normal serum homocysteine levels after 3 months of folate therapy. We conclude that folic acid treatment is effective in reduction of homocysteine levels in renal trans- plant recipients. Because homocystinuric patients have re- duced cardiovascular disease event rates after homocys- teine-lowering interventions, 8 further studies are necessary to evaluate homocysteine-lowering drugs’ effect on reduc- tion of cardiovascular mortality in renal transplant recipi- ents. REFERENCES 1. Hannedouche T, Kunz K, Muller S, et al: Adv Nephrol 28:287, 1998 2. Van Guldener C, Janssen MJFM, Surachno J, et al: Irish J Med Sci 164:22A, 1995 3. Sunder-Plassmann G, Floth A, Fodinger M: Curr Opin Urol 10:87, 2000 4. Ducloux D, Motte G, Challier B, et al: Arteriosel Thromb Vasc Biol 10:1894, 1997 5. Ubbink JB, Vermaak WJH, van der Merwe A, et al: J Nutr 124:1927, 1994 6. Bostom AG, Shemin D, Gohh RY, et al: Transplantation 69:2128, 2000 7. Bostom AG, Gohh RY, Beaulieu AJ, et al: Ann Intern Med 127:1089, 1997 8. Mudd SH, Skovby F, Levy HL, et al: Am J Hum Genet 37:1, 1985 From the Transplantation Unit, Hashemi Nejad Hospital, Iran University of Medical Sciences, Tehran, Iran. Address reprint requests to S. Savaj, Transplantation Unit, Hashemi Nejad Hospital, Iran University of Medical Sciences, Vanaque Square-19396, Tehran, Iran. E-mail: ssavaj@ hotmail.com © 2002 by Elsevier Science Inc. 0041-1345/02/$–see front matter 655 Avenue of the Americas, New York, NY 10010 PII S0041-1345(02)03160-3 Transplantation Proceedings, 34, 2419 (2002) 2419