Effect of MTHFR genotypes and hyperhomocysteinemia on patient and graft survival in kidney transplant recipients.

Background: The total homocysteine (tHcy) plasma level, which is partly determined by the MTHFR 677C-->T genotype, may be associated with vascular disease. We prospectively examined the influence of MTHFR genotypes (677C-->T, 1298A-->C) and tHcy plasma concentration on all cause mortality and graft outcomes of renal transplant recipients.

Methods: Baseline tHcy plasma levels of 189 patients (three groups with either the MTHFR 677CC, CT or TT genotype, including 63 patients in each group, were matched for age, gender, body mass index and creatinine clearance at baseline), were obtained between September 1996 and May 1997. Follow-up data (time until return to dialysis therapy, time and cause of death) were collected from April to June 1999. Kaplan-Meier survival estimations were calculated and plotted, the groups (three MTHFR 677C-->T genotype groups, or three MTHFR 1298A-->C genotype groups, or two groups with tHcy plasma levels above/below 15 micromol/L) were compared by log-rank test. Age, gender, body mass index (BMI), time since transplantation, serum creatinine, creatinine clearance, combined MTHFR 677C-->T/1298A-->C genotypes, tHcy, folate and vitamin B12 plasma levels were evaluated with regard to graft and patient survival in a multivariate Cox-proportional hazard regression model.

Results: During the follow-up period of 2.26 +/- 0.66 years, 9 patients died (5 in the TT, 2 in the CT and 2 in the CC genotype group; P = 0.34) and 22 returned to dialysis treatment (7 in the TT, 9 in the CT and 6 in the CC genotype group; P = 0.65). There was also no influence of MTHFR 1298A-->C genotypes (AA genotype, 114 patients; AC genotype, 64 patients; CC genotype, 11 patients) on patient or graft survival (P = 0.7087 and P = 0.1633, respectively). Two of 93 patients with a tHcy plasma level < or = 15 micromol/L died, in contrast to 7 of 96 patients in the tHcy > 15 micromol/L group, P = 0.0778. Two patients in the low tHcy group had to return to dialysis, in contrast to 20 patients in the high tHcy group (P = 0.0001). In the multivariate model there was no significant predictor of patient survival, and the serum creatinine was the only predictor of graft survival (P < 0.0001).

Conclusions: In summary, our study shows that neither MTHFR 677C-->T/1298A-->C genotypes nor hyperhomocysteinemia are independently associated with patient or graft survival following kidney transplantation.