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

Abstract

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/m²) 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.

Keywords: ASN; NKF; SCREAM; creatinine; cystatin C; glomerular filtration rate; race; risk factors.