Methylation cycle, arginine-creatine pathway and asymmetric dimethylarginine in paediatric renal transplant.
BACKGROUND
Hyperhomocysteinaemia represents an important cause of morbidity in recipients of renal transplants, but few investigations have been carried out to evaluate the status of the methylation cycle and its relation with levels of new cardiovascular biomarkers, such as asymmetric dimethylarginine (ADMA).


METHODS
Twenty-six children and adolescents aged 7-18 years (17 male, 9 female) with stable renal transplants were recruited for the study. None had received treatment with folate, vitamin B(12) or statins. Levels of ADMA in plasma and of components of the methylation cycle and arginine (Arg)-creatine pathway in plasma and urine were analysed by specific analytical methods. Results were compared to those obtained by us with identical methods in healthy children of similar age.


RESULTS
Concentrations of homocysteine (Hcys), S-adenosylhomocysteine (SAH) and ADMA were significantly higher, while S-adenosylmethionine (SAM)/SAH and Arg/ADMA ratios were significantly lower than controls. Arg/ADMA ratio correlated with plasma guanidinoacetate. The components of the methylation cycle, Hcys and SAH correlated with renal function.


CONCLUSIONS
Children with renal transplant showed low methylation power (SAM/SAH) mainly due to increased levels of SAH which acts as a cardiovascular biomarker. Elevated values of ADMA and low Arg/ADMA coefficients also represent a novel finding because it inhibits nitric oxide synthesis contributing to endothelial dysfunction and cardiovascular risk in such patients.
Andrade
Fernando
F
Division of Metabolism, Department of Pediatrics, Hospital de Cruces, Bilbao, Basque Country, 48903, Spain.
Rodríguez-Soriano
Juan
J
Prieto
José Angel
JA
Aguirre
Mireia
M
Ariceta
Gema
G
Lage
Sergio
S
Azcona
Isabel
I
Prado
Carmen
C
Sanjurjo
Pablo
P
Aldámiz-Echevarría
Luis
L
D058186:Acute Kidney Injury / Q000628:therapy*; D000293:Adolescent; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000652:urine; D002318:Cardiovascular Diseases / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D003401:Creatine / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D055316:Cystatin C / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D008745:Methylation; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
D015415:Biomarkers; D055316:Cystatin C; C487735:dimethylarginine; D001120:Arginine; D003404:Creatinine; D003401:Creatine