Discordances Between Creatinine- and Cystatin C-Based Estimated GFR and Adverse Clinical Outcomes in Routine Clinical Practice.

Rationale & Objective: Cystatin C is recommended for measuring estimated glomerular filtration rate (eGFR) when estimates based on creatinine (eGFR _cr ) 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 eGFR _cys and eGFR _cr and their association with clinical outcomes.
Study Design: Observational study.
Setting & Participants: 158,601 adults (48% women; mean age 62 years, eGFR _cr 80, and eGFR _cys 73mL/min/1.73/m ² ) undergoing testing for creatinine and cystatin C on the same day in connection with a health care encounter during 2010-2018 in Stockholm, Sweden.
Exposure: Percentage difference of eGFR _cys minus eGFR _cr (eGFR _diff ).
Outcome: Kidney failure with replacement therapy (KFRT), acute kidney injury (AKI), atherosclerotic cardiovascular disease (ASCVD), heart failure, and death.
Analytical Approach: Multivariable Cox proportional hazards regression.
Results: Discordances between eGFR _cr and eGFR _cys were common, with eGFR _cys being lower than eGFR _cr (negative eGFR _diff ) in most cases (65%). Patients with larger negative eGFR _diff were older, more often female, with higher eGFR _cr and albuminuria, and more comorbid conditions. Compared with patients with similar eGFR _cys and eGFR _cr , the lowest quartile (eGFR _cys > 27% lower than eGFR _cr ) had the higher HR of all study outcomes: AKI, 2.6 (95% CI, 2.4-2.9); KFRT, 1.4 (95% CI, 1.2-1.6); ASCVD, 1.4 (95% CI, 1.3-1.5); heart failure, 2.0 (95% CI, 1.9-2.2); and all-cause death, 2.6 (95% CI, 2.5-2.7). Conversely, patients in the highest quartile (positive eGFR _diff ) were at lower risk.
Limitations: Observational study, lack of information on indications for cystatin C testing.
Conclusions: Cystatin C testing in routine care shows that many patients have a lower eGFR _cys than eGFR _cr , and these patients have a higher risk of multiple adverse outcomes.
Plain-Language Summary: Clinicians require guidance when there are discrepancies between the estimated glomerular filtration rate based on creatinine (eGFR _cr ) and based on cystatin C (eGFR _cys ) in the same individual. Routine cystatin C testing in Sweden for over a decade permits exploration of how common and large these discrepancies are, and their associations with adverse clinical outcomes. In this observational study, we found that discordances between eGFR _cys and eGFR _cr are common, and 1 in 4 patients tested had an eGFR _cys > 28% lower than their eGFR _cr . We also show that an eGFR _cys that is lower than the eGFR _cr consistently identifies patients at higher risk of adverse outcomes, including cardiovascular events, kidney replacement therapy, acute kidney injury, and death.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)