What is the clinical evidence from this study?

Study design: Cohort. Population: Risk stratification for all-cause and cardiovascular deaths (n=4132). Intervention: EKFC cystatin C-based formula (EKFC eGFRcys) vs. CKD-EPI eGFRcys, EKFC eGFRcr, and CKD-EPI eGFRcr formulas. Primary outcome: All-cause and cardiovascular deaths (IDI 9.4%, NRI 39.7% (all-cause); IDI 6.7%, NRI 45.1% (CV)).

January 17, 2025Open Access

The Superiority of European Kidney Function Consortium Cystatin C-Based Formula for Risk Stratification of All-Cause and Cardiovascular Deaths in US Adults

Key Result

The EKFC cystatin C-based formula significantly improved prediction of 10-year all-cause (IDI 9.4%; NRI 39.7%) and cardiovascular deaths (IDI 6.7%; NRI 45.1%) compared to the CKD-EPI formula.

Study Design

Type

Cohort (n=4,132)

Multicenter

Yes

Structured PICO

Does the EKFC cystatin C-based formula improve prediction of all-cause and cardiovascular deaths compared to other eGFR formulas in US adults?

Population

4,132 participants from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2002 representing the general US population

Intervention

Risk stratification using the European Kidney Function Consortium (EKFC) cystatin C-based formula (EKFC eGFRcys)

Comparator

Risk stratification using CKD-EPI cystatin C-based formula, EKFC creatinine-based formula, and CKD-EPI creatinine-based formula

Outcome

All-cause and cardiovascular deaths over a median follow-up of 17.4 yearshard clinical

The EKFC cystatin C-based formula provides superior risk stratification for all-cause and cardiovascular mortality compared to CKD-EPI and creatinine-based formulas in the general US population.

Main Result

Effect estimate: IDI 9.4%, NRI 39.7% (all-cause); IDI 6.7%, NRI 45.1% (CV)

Abstract

Introduction: We intended to compare the predictive value for all-cause and cardiovascular deaths between estimated glomerular filtration rate (eGFR) derived from the European Kidney Function Consortium (EKFC) cystatin C-based formula, the EKFC creatinine-based formula, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) cystatin C- or creatinine-based formulas. Methods: Overall, 4,132 participants from the National Health and Nutrition Examination Survey between 1999 and 2002 were included, and death information was obtained through the National Death Index. To compare predictive accuracy between EKFC eGFRcys (EKFC cystatin C-based formula), CKD-EPI eGFRcys (CKD-EPI cystatin C-based formula), EKFC eGFRcr (EKFC creatinine-based formula), and CKD-EPI eGFRcr (CKD-EPI creatinine-based formula), we conducted time-dependent receiver operator characteristic (ROC) curves and reclassification analysis. Results: During a median follow-up of 17.4 years, a total of 1,987 all-cause and 530 cardiovascular deaths were confirmed. Restricted cubic splines analyses showed that reduced EKFC eGFRcys was linearly related to higher risks of all-cause and cardiovascular deaths (p for nonlinearity > 0.05). Time-dependent ROC curves suggested that EKFC eGFRcys exhibited higher predictive ability than CKD-EPI eGFRcys, EKFC eGFRcr, and CKD-EPI eGFRcr at 5-year and 10-year follow-ups. For 10-year all-cause deaths, EKFC eGFRcys yielded significant improvement over CKD-EPI eGFRcr (integrated discrimination improvement IDI, 9.4%; net reclassification improvement NRI, 39.7%). Similar improvement was observed in 10-year cardiovascular deaths when comparing EKFC eGFRcys to CKD-EPI eGFRcr (IDI, 6.7%; NRI, 45.1%). Conclusion: The EKFC eGFRcys outperformed CKD-EPI eGFRcys, EKFC eGFRcr, and CKD-EPI eGFRcr in predicting all-cause and cardiovascular deaths, providing the possibility to utilize EKFC eGFRcys in the stratification of death risk among the general US population.

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