title: Arginine, dimethylated arginine and homoarginine in relation to cardiovascular risk in patients with moderate chronic kidney disease.
abstract: OBJECTIVE
  Arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine/ADMA ratio and homoarginine could potentially affect nitric oxide production and have been studied in relation to cardiovascular risk (CVR) in various clinical populations. Prospective studies on the CVR associated with arginine/ADMA ratio and homoarginine in patients with moderate chronic kidney disease (CKD) are still scarce. We have studied how arginine, homoarginine and dimethylated arginine can predict cardiovascular events in such a population.
  
  
  METHODS
  We measured plasma concentrations of arginine (P-arginine), ADMA (P-ADMA), SDMA (P-SDMA), homoarginine (P-homoarginine) and other covariates in 160 patients with predialytic CKD (mean age 57 years and mean eGFR 43 mL/min/1.73 m(2)) and followed them for 58 months in median. The risks of fatal and non-fatal cardiovascular events associated with the predictors were evaluated with multivariable Cox proportional hazard analysis.
  
  
  RESULTS
  There were 31 cardiovascular events during the observation period. In a multivariable model adjusted for age, sex, previous cardiovascular disease, P-cystatin C and P-homoarginine, the hazard ratio (HR) associated with an increase in arginine/ADMA ratio by 10 was 0.83 (P=0.03). The HR of a 1 μmol/L increase in P-homoarginine in the same model was 1.78 (P=0.01). A statistically significant interaction between P-homoarginine and P-cystatin C was found in an extended multivariable model. P-SDMA was not associated with increased CVR after adjustment for basic covariates.
  
  
  CONCLUSIONS
  This study demonstrates a negative association between arginine/ADMA ratio and CVR in CKD patients and a positive association between P-homoarginine and CVR. The latter is in contrast to what has been demonstrated by others.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Medical Biochemistry, St. Olavs Hospital, Trondheim University Hospital, Norway. Electronic address: gunhild.garmo.hov@stolav.no.
authors.forename: Gunhild Garmo
authors.initials: GG
authors.lastname: Hov
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Knut Ivar
authors.initials: KI
authors.lastname: Aasarød
authors.affiliation: Department of Medical Biochemistry, St. Olavs Hospital, Trondheim University Hospital, Norway.
authors.forename: Erling
authors.initials: E
authors.lastname: Sagen
authors.affiliation: Department of Medical Biochemistry, St. Olavs Hospital, Trondheim University Hospital, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Åsberg
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D006709:Homoarginine / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C487735:dimethylarginine; D006709:Homoarginine; D001120:Arginine
keywords: ADMA; Arginine/ADMA ratio; Cardiovascular risk; Chronic kidney disease; Homoarginine