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.

Automated summary

Routine cystatin C testing provides real-world evidence about the differences between estimated glomerular filtration rate based on cystatin C and creatinine, and their association with various clinical outcomes. This observational study in Sweden found that patients with lower eGFR(cys) than eGFR(cr) had a higher risk of kidney failure, acute kidney injury, atherosclerotic cardiovascular disease, heart failure, and death.