High cysteine levels in renal transplant recipients - Relationship with hyperhomocysteinemia and 5,10-MTHFR polymorphism

Background Long-term survival of renal transplant recipients seems to be in fluenced by the occurrence of thromboembolic complications and cardiovascul ar disease. Preliminary data available in the Literature found high levels of cysteine (Cy) as a risk factor for deep venous thrombosis independently of high homocysteine (tHcy) levels, but no data are available about Cy leve ls in renal transplant recipients. Methods. To investigate Cy, tHcy, and plasminogen activator inhibitor-1 (PA I-1) levels and the prevalence of 5,10-methylenetetrahydrofolate reductase (MTHFR) in renal transplantation, we studied 70 stable renal transplant rec ipients and 66 age- and sex-matched normal subjects as controls. Results. Cy, tHcy, and PAI-1 levels were significantly higher in renal tran splant recipients with respect to controls (Cy: 254 mu mol/L [117-466] vs. 198 mu mol/L [99-331], P <0.001; tHcy: 17.0 mu mol/L [4.0-68] vs. 8.1 mu mo l/L [2.0-24.0], P <0.00001; PAI-1: 16.8 IU/ml [5.1-45.5] vs. 7.9 IU/ml [4.0 -18.0], P<0.00001). High Cy levels were detected in 35.8% of patients. Hype rhomocysteinemia, both in the fasting state and postmethionine loading test , was diagnosed in 90% of cases. The odds ratios for Cy and tHcy levels wit hin the fourth quartile with respect to the other quartiles were markedly i ncreased in renal transplant recipients even after adjustment for prevalent cardiovascular risk factors, glomerular filtration rate, tHcy and, Cy, res pectively (Cy: 29.0 <mu>mol/L [95% CI 7.0-111]; tHcy: 29.9 mu mol/L [95% CI 7.5-118.1]). Pasting tHcy levels correlated well with PAI-1 (r=0.65; P <0. 0001) but not with Cy levels (r=0.10; P=0.4). The prevalence of the MTHFR 6 77TT genotype in renal transplant recipients was not significantly higher i n patients than in controls (mutant allele frequency: 0.48 in patients and 0.47 in controls) and was associated with significantly higher fasting and postmethionine tHcy levels both in controls and patients. After 2 months of vitamin supplementation, tHcy (Pre: 17.0 mu mol/L 14.0-68]; Post: 7.5 mu m ol/L [2.3-21.9]; P<0.0001) and PAI-1 levels (Pre: 16.8 IU/ml [5.1-45.5]; Po st: 10 IU/ml [2.0-25]; P<0.001) were significantly decreased, whereas Cy le vels showed a small decrease that did not reach statistical significance (P re: 254 mu mol/L [117-4661; Post: 209 mu mol/L [168-300]; P=0.3). Patients with the MTHFR 677TT genotype had the major percentage of decrease of tHcy levels with respect to the other genotypes. Conclusion. In conclusion, this study demonstrates the presence of elevated Cy plasma levels in renal transplant recipients. Vitamin supplementation r educes tHcy but not Cy levels, and the amount of decrease seems to be influ enced by the MTHFR genotype.