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 influenced by the occurrence of thromboembolic complications and cardiovascular 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 levels in renal transplant recipients.


METHODS
To investigate Cy, tHcy, and plasminogen activator inhibitor-1 (PAI-1) levels and the prevalence of 5,10-methylenetetrahydrofolate reductase (MTHFR) in renal transplantation, we studied 70 stable renal transplant recipients and 66 age- and sex-matched normal subjects as controls.


RESULTS
Cy, tHcy, and PAI-1 levels were significantly higher in renal transplant recipients with respect to controls (Cy: 254 micromol/L [117-466] vs. 198 micromol/L [99-331], P<0.001; tHcy: 17.0 micromol/L [4.0-68] vs. 8.1 micromol/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. Hyperhomocysteinemia, both in the fasting state and postmethionine loading test, was diagnosed in 90% of cases. The odds ratios for Cy and tHcy levels within the fourth quartile with respect to the other quartiles were markedly increased in renal transplant recipients even after adjustment for prevalent cardiovascular risk factors, glomerular filtration rate, tHcy and, Cy, respectively (Cy: 29.0 micromol/L [95% CI 7.0-111]; tHcy: 29.9 micromol/L [95% CI 7.5-118.1]). Fasting 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 677TT genotype in renal transplant recipients was not significantly higher in 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 micromol/L [4.0-68]; Post: 7.5 micromol/L [2.3-21.9]; P<0.0001) and PAI-1 levels (Pre: 16.8 IU/ml [5.1-45.5]; Post: 10 IU/ml [2.0-25]; P<0.001) were significantly decreased, whereas Cy levels showed a small decrease that did not reach statistical significance (Pre: 254 micromol/L [117-466]; Post: 209 micromol/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.


CONCLUSIONS
In conclusion, this study demonstrates the presence of elevated Cy plasma levels in renal transplant recipients. Vitamin supplementation reduces tHcy but not Cy levels, and the amount of decrease seems to be influenced by the MTHFR genotype.
Marcucci
R
R
Istituto di Clinica Medica Generale e Cardiologia, Università di Firenze, and Renal Unit, Careggi Hospital, Florence, Italy.
Fedi
S
S
Brunelli
T
T
Pepe
G
G
Prisco
D
D
Rosati
A
A
Zanazzi
M
M
Bertoni
E
E
Abbate
R
R
Salvadori
M
M
D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D000328:Adult; D003545:Cysteine / Q000097:blood*; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008875:Middle Aged; D010088:Oxidoreductases / Q000235:genetics; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011736:Pyridoxine / Q000627:therapeutic use; D014805:Vitamin B 12 / Q000627:therapeutic use
D017395:Plasminogen Activator Inhibitor 1; D006710:Homocysteine; D005492:Folic Acid; D010088:Oxidoreductases; D045103:5,10-Methylenetetrahydrofolate Reductase (FADH2); D042965:Methylenetetrahydrofolate Reductase (NADPH2); D003545:Cysteine; D011736:Pyridoxine; D014805:Vitamin B 12