Discordances Between Creatinine- and Cystatin C–Based Estimated GFR and Adverse Clinical Outcomes in Routine Clinical Practice
Juan Jesús Carrero, Edouard L. Fu, Yingying Sang, Shoshana H. Ballew, Marie Evans, Carl‐Gustaf Elinder, Peter Bárány, Lesley A. Inker, Andrew S. Levey, Josef Coresh, Morgan E. Grams
Abstract
Rationale & ObjectiveCystatin C is recommended for estimating glomerular filtration rate (eGFR) when estimates based on creatinine (eGFRcr) are not thought to be accurate enough for clinical decision making. While global adoption is slow, routine cystatin C testing in Sweden has been available for over a decade, providing real-world evidence about the magnitude of differences between eGFRcys and eGFRcr and their association with clinical outcomes.Study designObservational study.Setting & Participants158,601 adults (48% women, mean 62 years, eGFRcr 80 and eGFRcys 73 ml/min/1.73/m2) undergoing testing for creatinine and cystatin C on the same day in connection with a healthcare encounter during 2010-2018 in Stockholm, Sweden.ExposuresPercentage difference of eGFRcys minus eGFRcr (eGFRdiffcys-cr).OutcomesKidney failure with replacement therapy (KFRT), acute kidney injury (AKI), atherosclerotic cardiovascular disease (ASCVD), heart failure (HF) and death.Analytical ApproachMultivariable Cox proportional hazards regression.ResultsDiscordances between eGFRcr and eGFRcys were common, with eGFRcys being lower than eGFRcr (negative eGFRdiffcys-cr) in most cases (65%). Patients with larger negative eGFRdiffcys-cr were older, more often female, with higher eGFRcr and albuminuria, and more comorbid conditions. Compared to patients with similar eGFRcys and eGFRcr, the lowest quartile (eGFRcys >27% lower than eGFRcr) had a higher hazard ratio (HR) of all study outcomes (AKI HR 2.6; 95% CI 2.4-2.9, KFRT 1.4; 1.2-1.6, ASCVD 1.4; 1.3-1.5, HF 2.0; 1.9-2.2 and all-cause death 2.6; 2.5-2.7). Conversely, patients in the highest quartile (positive eGFRdiffcys-cr) were at lower risk.LimitationsObservational study, lack of information on indications for Cystatin C testing.ConclusionsCystatin C testing in routine care shows that many patients have lower eGFRcys than eGFRcr, and these patients had a higher risk of multiple adverse outcomes.