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) 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 and eGFR and their association with clinical outcomes.

STUDY DESIGN

Observational study.

SETTING & PARTICIPANTS: 158,601 adults (48% women; mean age 62 years, eGFR 80, and eGFR 73mL/min/1.73/m) 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 minus eGFR (eGFR).

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 and eGFR were common, with eGFR being lower than eGFR (negative eGFR) in most cases (65%). Patients with larger negative eGFR were older, more often female, with higher eGFR and albuminuria, and more comorbid conditions. Compared with patients with similar eGFR and eGFR, the lowest quartile (eGFR > 27% lower than eGFR) 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) 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 than eGFR, 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) and based on cystatin C (eGFR) 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 and eGFR are common, and 1 in 4 patients tested had an eGFR > 28% lower than their eGFR. We also show that an eGFR that is lower than the eGFR consistently identifies patients at higher risk of adverse outcomes, including cardiovascular events, kidney replacement therapy, acute kidney injury, and death.