Estimated GFR is biased by non-traditional cardiovascular risk factors

Am J Nephrol. 2015;41(1):7-15. doi: 10.1159/000371557. Epub 2015 Jan 23.


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.

Conclusion: Both creatinine- and cystatin C-based eGFR are influenced by nontraditional risk factors, which may bias risk prediction by eGFR in longitudinal studies.

MeSH terms

  • Arginine / analogs & derivatives*
  • Arginine / blood*
  • Bias
  • Creatinine / blood
  • Cross-Sectional Studies
  • Cystatin C / blood
  • Female
  • Glomerular Filtration Rate*
  • Homeostasis
  • Humans
  • Insulin Resistance / physiology*
  • Male
  • Middle Aged
  • Risk Factors


  • Cystatin C
  • dimethylarginine
  • Arginine
  • Creatinine