Estimated GFR is biased by non-traditional cardiovascular risk factors

Abstract

Background: Estimated glomerular filtration rate (eGFR) based on either cystatin C or creatinine perform similarly in estimating measured GFR, but associate differently with cardiovascular disease (CVD) and mortality. This could be due to confounding by non-GFRrelated traits associated with cystatin C and creatinine levels. We investigated non-GFRrelated associations between eGFR and two types of non-traditional risk factors for CVD and death: L-arginine/dimethylarginine metabolism and insulin resistance. <p>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). <p>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. <p>Conclusion: Both creatinine- and cystatin C-based eGFR are influenced by non-traditional risk factors, which may bias risk prediction by eGFR in longitudinal studies.