title: Symmetric dimethylarginine as predictor of graft loss and all-cause mortality in renal transplant recipients.
abstract: BACKGROUND
  Elevated symmetric dimethylarginine (SDMA) has been shown to predict cardiovascular events and all cause mortality in diverse populations. The potential role of SDMA as a risk marker in renal transplant recipients (RTR) has not been investigated.
  
  
  METHODS
  We analyzed SDMA in the placebo arm of the Assessment of Lescol in Renal Transplantation study, a randomized controlled trial of fluvastatin in RTR. Mean follow-up was 5.1 years. Patients were grouped into quartiles based on SDMA levels at study inclusion. Relationships between SDMA and traditional risk factors for graft function and all-cause mortality were analyzed in 925 RTR using univariate and multivariate survival analyses.
  
  
  RESULTS
  In univariate analysis, SDMA was significantly associated with renal graft loss, all-cause death, and major cardiovascular events. After adjustment for established risk factors including estimated glomerular filtration rate, an elevated SDMA-level (4th quartile, >1.38 μmol/L) was associated with renal graft loss; hazard ratio (HR), 5.51; 95% confidence interval (CI), 1.95-15.57; P=0.001, compared to the 1st quartile. Similarly, SDMA in the 4th quartile was independently associated with all-cause mortality (HR, 4.56; 95% CI, 2.15-9.71; P<0.001), and there was a strong borderline significant trend for an association with cardiovascular mortality (HR, 2.86; 95% CI, 0.99-8.21; P=0.051).
  
  
  CONCLUSIONS
  In stable RTR, an elevated SDMA level is independently associated with increased risk of all-cause mortality and renal graft loss.
authors.affiliation: 1 Division of Nephrology, Department of Organ Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway. 2 Division of Nephrology, Department of Medicine, Oslo University Hospital Ullevål, Oslo, Norway. 3 Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria. 4 Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands. 5 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. 6 Synlab Center of Laboratory Diagnostics, Heidelberg, Germany. 7 Medical Faculty Mannheim, Mannheim Institute of Public Health, Social and Preventive Medicine, University of Heidelberg, Mannheim, Germany. 8 Department of Medicine, Division of Nephrology, Vestfold Hospital, Tønsberg, Norway. 9 Department of Preventive Medicine and Unit of Biostatistics and Epidemiology, Oslo University Hospital Ullevål, Oslo, Norway. 10 Division of Nephrology, Department of Internal Medicine, Uppsala University Hospital, Uppsala, Sweden. 11 British Heart Foundation, Glasgow Cardiovascular Research Centre, Glasgow, Scotland, United Kingdom. 12 Address correspondence to: Hege Pihlstrøm, M.D., Department of Organ Transplantation, Division of Nephrology, Oslo University Hospital, Rikshospitalet, P.B. 4950 Nydalen, 0424 Oslo, Norway.
authors.forename: Hege
authors.initials: H
authors.lastname: Pihlstrøm
authors.forename: Geir
authors.initials: G
authors.lastname: Mjøen
authors.forename: Dag Olav
authors.initials: DO
authors.lastname: Dahle
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.forename: Karsten
authors.initials: K
authors.lastname: Midtvedt
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.forename: Sadollah
authors.initials: S
authors.lastname: Abedini
authors.forename: Ingar
authors.initials: I
authors.lastname: Holme
authors.forename: Bengt
authors.initials: B
authors.lastname: Fellström
authors.forename: Alan
authors.initials: A
authors.lastname: Jardine
authors.forename: Hallvard
authors.initials: H
authors.lastname: Holdaas
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D051437:Renal Insufficiency / Q000175:diagnosis / Q000401:mortality / Q000601:surgery*; D012307:Risk Factors; D013997:Time Factors; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; C024917:symmetric dimethylarginine; D000077340:Fluvastatin; D001120:Arginine