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Discordances Between Creatinine- and Cystatin C-Based Estimated GFR and Adverse Clinical Outcomes in Routine Clinical
Juan-Jesús Carrero1, Edouard L Fu2, Yingying Sang3
1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Division of Nephrology, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Insights
Routine cystatin C testing reveals many patients have a lower estimated glomerular filtration rate (eGFR) than creatinine-based estimates. This eGFR difference is linked to increased risks of adverse outcomes, including kidney failure and cardiovascular events.
Area of Science:
- Nephrology
- Clinical Chemistry
- Epidemiology
Background:
- Estimated glomerular filtration rate (eGFR) is crucial for clinical decision-making.
- Creatinine-based eGFR (eGFRcr) may not always be accurate.
- Cystatin C-based eGFR (eGFRcys) is recommended when eGFRcr is insufficient.
Purpose of the Study:
- To investigate the prevalence and magnitude of differences between eGFRcys and eGFRcr in a real-world setting.
- To assess the association of these eGFR discrepancies with adverse clinical outcomes.
Main Methods:
- Observational study of 158,601 adults in Stockholm, Sweden (2010-2018).
- Simultaneous measurement of creatinine and cystatin C.
- Analysis of eGFR differences (eGFRdiff) and association with outcomes using multivariable Cox regression.
Main Results:
- Discordances between eGFRcys and eGFRcr were common (65% had lower eGFRcys).
- Patients with a significantly lower eGFRcys (eGFRcys >27% lower than eGFRcr) showed higher risks for AKI, KFRT, ASCVD, heart failure, and death.
- Conversely, positive eGFRdiff indicated lower risk.
Conclusions:
- Routine cystatin C testing identifies a substantial number of patients with lower eGFRcys compared to eGFRcr.
- These discrepancies are associated with increased risks of severe adverse health outcomes.
- eGFRcys provides valuable prognostic information beyond eGFRcr.
Rationale & Objective:
Cystatin C is recommended for measuring estimated 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 Design:
Observational study.
Setting & Participants:
158,601 adults (48% women; mean age 62 years, eGFRcr 80, and eGFRcys 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 eGFRcys minus eGFRcr (eGFRdiff).
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 eGFRcr and eGFRcys were common, with eGFRcys being lower than eGFRcr (negative eGFRdiff) in most cases (65%). Patients with larger negative eGFRdiff were older, more often female, with higher eGFRcr and albuminuria, and more comorbid conditions. Compared with patients with similar eGFRcys and eGFRcr, the lowest quartile (eGFRcys > 27% lower than eGFRcr) 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 eGFRdiff) 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 eGFRcys than eGFRcr, 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 (eGFRcr) and based on cystatin C (eGFRcys) 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 eGFRcys and eGFRcr are common, and 1 in 4 patients tested had an eGFRcys > 28% lower than their eGFRcr. We also show that an eGFRcys that is lower than the eGFRcr consistently identifies patients at higher risk of adverse outcomes, including cardiovascular events, kidney replacement therapy, acute kidney injury, and death.
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