title: Methylation cycle, arginine-creatine pathway and asymmetric dimethylarginine in paediatric renal transplant.
abstract: 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.
authors.affiliation: Division of Metabolism, Department of Pediatrics, Hospital de Cruces, Bilbao, Basque Country, 48903, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Andrade
authors.forename: Juan
authors.initials: J
authors.lastname: Rodríguez-Soriano
authors.forename: José Angel
authors.initials: JA
authors.lastname: Prieto
authors.forename: Mireia
authors.initials: M
authors.lastname: Aguirre
authors.forename: Gema
authors.initials: G
authors.lastname: Ariceta
authors.forename: Sergio
authors.initials: S
authors.lastname: Lage
authors.forename: Isabel
authors.initials: I
authors.lastname: Azcona
authors.forename: Carmen
authors.initials: C
authors.lastname: Prado
authors.forename: Pablo
authors.initials: P
authors.lastname: Sanjurjo
authors.forename: Luis
authors.initials: L
authors.lastname: Aldámiz-Echevarría
mesh_terms: 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
chemical_list: D015415:Biomarkers; D055316:Cystatin C; C487735:dimethylarginine; D001120:Arginine; D003404:Creatinine; D003401:Creatine