Comparative Prognostic Assessment of European Kidney Function Consortium Equations for Mortality Prediction: A...

The European Kidney Function Consortium (EKFC) has introduced equations for estimated glomerular filtration rate (eGFR) using serum creatinine (Cr) and cystatin C (Cys). While their diagnostic accuracy is established, their comparative prognostic value for long-term mortality in the general population is not well defined. This study compared the prognostic performance of three EKFC equations - creatinine-based (EKFC-eGFRcr), Cys-based (EKFC-eGFRcys), and the combined (EKFC-eGFRcrcys) model - for predicting all-cause and cardiovascular (CV) mortality.

We analyzed a population-based cohort of 4,519 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2002. eGFR was calculated using all three EKFC variations (EKFC-eGFRcr, EKFC-eGFRcys, and EKFC-eGFRcrcys). The primary and secondary endpoints were all-cause and CV mortality, respectively, through December 31, 2019. Predictive improvements were evaluated using integrated discrimination improvement (IDI), net reclassification improvement (NRI), and number needed to measure (NNM).

The eGFR value calculated by the EKFC-eGFRcys, EKFC-eGFRcr, and EKFC-eGFRcrcys was 78.92 ± 22.98, 84.45 ± 23.21, and 81.68 ± 22.13 mL/min/1.73 m2, respectively. Over a median follow-up of 211 months, all three eGFR models were independent predictors of mortality (all p < 0.001). Restricted cubic spline regression revealed significant non-linear, inverse associations between all eGFR measures and adjusted mortality risks (all p for non-linearity < 0.001). Compared to EKFC-eGFRcr, EKFC-eGFRcys significantly improved risk reclassification for all-cause mortality (categorical NRI = 15.9%; 95% CI: 14.1-17.8%; NNM = 7). The combined EKFC-eGFRcrcys also outperformed the Cr-only model (NRI = 8.9%; NNM = 12). However, EKFC-eGFRcys demonstrated modestly better performance than the combined equation (NRI = 7.0%; NNM = 15), suggesting limited incremental value in adding Cr to Cys. The superiority of EKFC-eGFRcys was primarily driven by improved classification of non-events.

The EKFC-eGFRcys equation provides superior prognostic value for all-cause and CV mortality compared to both Cr-based and combined EKFC equations. Notably, the combined model offered no prognostic advantage over Cys alone. These findings highlight the clinical importance of Cys-based eGFR for accurate risk stratification in the general population.