title: Estimated GFR is biased by non-traditional cardiovascular risk factors.
abstract: BACKGROUND
  Estimated glomerular filtration rate (eGFR) based on either cystatin C or creatinine performs similarly in estimating measured GFR, but associate differently with cardiovascular disease (CVD) and mortality. This could be due to confounding by non-GFR-related traits associated with cystatin C and creatinine levels. We investigated non-GFR-related associations between eGFR and two types of nontraditional risk factors for CVD and death: L-arginine/dimethylarginine metabolism and insulin resistance.
  
  
  METHODS
  GFR was measured via iohexol clearance in a cross-sectional study of 1,624 middle-aged persons from the general population without CVD, diabetes or chronic kidney disease. The dimethylarginines were measured using liquid chromatography tandem mass spectrometry (LC-MSMS). Insulin resistance was determined by the homeostasis model assessment (HOMA-IR).
  
  
  RESULTS
  Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), the L-arginine/ADMA ratio and insulin resistance were associated with creatinine-based eGFR after accounting for measured GFR in multivariable adjusted analyses. The cystatin C-based eGFR showed a similar residual association with SDMA; an oppositely directed, borderline significant association with ADMA; and a stronger residual association with insulin resistance compared with eGFR based on creatinine.
  
  
  CONCLUSIONS
  Both creatinine- and cystatin C-based eGFR are influenced by nontraditional risk factors, which may bias risk prediction by eGFR in longitudinal studies.
authors.affiliation: Department of Nephrology, University Hospital of North Norway, UNN, Tromsø Norway.
authors.forename: Toralf
authors.initials: T
authors.lastname: Melsom
authors.forename: Ole Martin
authors.initials: OM
authors.lastname: Fuskevåg
authors.forename: Ulla Dorte
authors.initials: UD
authors.lastname: Mathisen
authors.forename: Harald
authors.initials: H
authors.lastname: Strand
authors.forename: Jørgen
authors.initials: J
authors.lastname: Schei
authors.forename: Trond
authors.initials: T
authors.lastname: Jenssen
authors.forename: Marit
authors.initials: M
authors.lastname: Solbu
authors.forename: Bjørn Odvar
authors.initials: BO
authors.lastname: Eriksen
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D015982:Bias; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D055316:Cystatin C / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D055316:Cystatin C; C487735:dimethylarginine; D001120:Arginine; D003404:Creatinine