Determinants of plasma aminothiols levels in renal transplant recipients

Elevated homocysteine (Hcys) plasma levels is a common finding in renal transplant recipients (RTRs) and may represent a risk factor for vascular disease in these subjects. Recently, an atherogenic role has also been hypotesized for Cysteine (Cys) a thiol-containing amino acid with a structure similar to Hcys. The aim of this study was to analyze 1) Hcys and Cys plasma levels in a group of stable RTRs; 2) the relationship among total Hcys and Cys, renal function and serum vitamin B12 and folate levels; 3) the influence of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms on both thiols.
Methods. One hundred-eight stable RTRs already evaluated for routine follow-up during 2000 were included in the study (56 men, 52 women, mean age 46.3 ± 11.9 years;) as well as 93 healthy control subjects [1]. Plasma Hcys and Cys were measured by HPLC with fluorescent detection. Plasma folate and vitamin B12 were measured by ion capture assay and microparticle enzyme immunoassay, respectively (Abbott AxSYM automatic analyzer). MTHFR C677T and A1298C gene polymorphisms were genotyped by PCR-RFLP.
Results. Hcys levels were slightly increased in RTRs compared to controls although not significantly (11.4±8.2 vs 8.9±5.4 μmol/L; p>.05) whereas Cys levels were significantly increased (273± 49 μmol/L vs 210 ± 35, p<0.05). Hcys in RTRs showed a significant inverse correlation with GFR (r=-0.49;P<.01) and a weak inverse correlation with serum folate (r=-0.23; p>0.05) and vitamin B12 (r=-0.18; P>0.05). A significant correlation of Cys levels with the age of the patients (r=0.31;p<0.01) was observed in RTRs. Patients carrying the MTHFR 677TT genotype had significantly higher Hcys levels than those with other genotypes, although this difference disappeared when Hcys was adjusted for glomerular filtration rate. Cys levels were unaffected by either MTHFR polymorphisms.
Conclusions. The only strong determinant of plasma Hcys in RTRs is glomerular filtration rate whereas folate, vitamin B12 and MTHFR polymorphisms have a minor effect. Cys levels were increased in older patients but no association with renal function, vitamin levels or MTHFR genotype was found.