title: Plasma symmetric dimethylarginine reference limits from the Framingham offspring cohort.
abstract: BACKGROUND
  Symmetric dimethylarginine (SDMA) is a by-product of protein methylation. Once released from proteins, SDMA is eliminated by the kidneys; consequently, plasma concentration has been suggested as a sensitive marker of renal function. Furthermore, recent work implicates SDMA in the pathogenesis of cardiovascular disease. To date, reference limits for SDMA plasma concentrations in healthy individuals are lacking.
  
  
  METHODS
  This study defined reference limits for plasma SDMA concentrations in 840 relatively healthy individuals of the Offspring Cohort from Framingham Heart Study (mean age 56 years, 61% women). Plasma SDMA concentrations were determined by LC-MS/MS using a stable isotope dilution assay.
  
  
  RESULTS
  The median SDMA concentration in the reference sample was 0.37 μmol/L (Q1, Q3:0.32, 0.43 μmol/L) and the reference limits were 0.225 and 0.533 (2.5th and 97.5th percentile). In a multivariable regression model, serum creatinine, age and total homocysteine were positively associated with SDMA (p<0.001 for all), whereas the body mass index and diastolic blood pressure were inversely related to SDMA (p-values<0.01 and 0.03, respectively).
  
  
  CONCLUSIONS
  This study reports plasma SDMA reference limits from the community-based Framingham Heart Study. Plasma SDMA concentration was related positively to advancing age, but inversely to renal function. These reference limits may allow the identification of individuals with raised plasma SDMA concentrations.
authors.affiliation: Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. schwedhelm@uke.uni-hamburg.de
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.forename: Vanessa
authors.initials: V
authors.lastname: Xanthakis
authors.forename: Renke
authors.initials: R
authors.lastname: Maas
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Sullivan
authors.forename: Dorothee
authors.initials: D
authors.lastname: Atzler
authors.forename: Nicole
authors.initials: N
authors.lastname: Lüneburg
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Glazer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Riederer
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
mesh_terms: D000367:Age Factors; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D001794:Blood Pressure; D015992:Body Mass Index; D002853:Chromatography, Liquid; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000175:diagnosis; D007677:Kidney Function Tests / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011865:Radioisotope Dilution Technique; D012016:Reference Values; D053719:Tandem Mass Spectrometry; D014481:United States
chemical_list: D015415:Biomarkers; D006710:Homocysteine; C024917:symmetric dimethylarginine; D001120:Arginine; D003404:Creatinine