Abstract

BACKGROUND: The consequences for health outcomes of the discordance in cystatin C-based (eGFRcys) and creatinine-based (eGFRcr) estimated glomerular filtration rates are gaining attention. However, the association of discordance with all-cause mortality in the general population has not been explored. METHODS: A total of 325 356 UK Biobank participants, 40 to 69 years of age, were followed for a median of 13.7 years. eGFR was calculated using both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009/2012 equations and the European Kidney Function Consortium (EKFC) equations. Differences were expressed as the absolute difference (eGFRcys ? eGFRcr, where discordance was defined as ±15 mL/min/1.73 m2 difference) and relative difference (eGFRcys/eGFRcr, where discordance was defined as eGFRcys < 60% eGFRcr). Hazard ratios (HRs) for mortality were estimated using multivariable Cox proportional hazards models. RESULTS: Among the participants, 15.5% had a discordant lower absolute eGFRcys, and 8.5% had a discordant higher absolute eGFRcys. Participants with discordant lower absolute eGFRcys (both CKD-EPI and EKFC equations) were older, more frequently male, had higher body mass index (BMI) and blood pressure, more comorbidities, and did less physical activity. A total of 26 465 deaths occurred. Participants with discordant lower eGFRcys had a 53% higher risk of mortality (HR = 1.53: 95% CI, 1.48–1.57), while those with discordant higher eGFRcys had a 30% lower risk (HR = 0.70: 95% CI, 0.66–0.75) compared to those with concordant eGFR. Those with discordance of lower relative eGFRcys had doubled risk of mortality (HR = 2.25: 95% CI, 2.04–2.47). CONCLUSIONS: eGFR discordance was prevalent and associated with mortality in general populations. These results support broader use of cystatin C for risk stratification of mortality. © Association for Diagnostics & Laboratory Medicine 2025.