Evaluating Long-Term Outcomes Across eGFR Equations in Older Adults

The current diagnostic threshold for chronic kidney disease (CKD; estimated glomerular filtration rate [GFR; eGFR] < 60 ml/min per 1.73 m²) may lead to overdiagnosis in older adults. Additionally, no consensus exists regarding the optimal eGFR equation for use in older adults, despite considerable variability in calculations between equations. We investigated the impact of using eGFR equations validated for older populations (Berlin Initiative Study 1 [BIS1] and European Kidney Function Consortium [EKFC]) in place of the 2021 CKD-Epidemiology collaboration (EPI) creatinine equation (CKD-EPI₂₀₂₁) and assessed the implications of an age-adapted CKD definition (eGFR < 45 ml/min per 1.73 m²).

This cohort study used data from the aspirin in reducing events in the elderly (ASPREE) trial and its observational follow-up (ASPREE-eXtension). ASPREE enrolled community-dwelling older adults. Separate survival analyses compared the risk of reduced disability-free survival (DFS), its components, or major adverse cardiovascular events (MACE) between participants reclassified to a different CKD stage versus those who remained within the same stage when changing from CKD-EPI₂₀₂₁ to BIS1EKFC. Associations between eGFR and health outcomes were analyzed using restricted cubic splines referenced to eGFR of 75 ml/min per 1.73 m².

Among 17,686 participants (mean age 75.1 ± 4.3 years), BIS1, and EKFC yielded eGFR values 12 to 15 ml/min per 1.73 m² lower than CKD-EPI₂₀₂₁; increasing CKD prevalence from 21% to 37%-46%. Most participants moved to a higher CKD stage when changing from CKD-EPI₂₀₂₁ to BIS1, or EKFC; however, long-term outcomes were similar across reclassified and nonreclassified groups. Across all equations, risks of reduced DFS, all-cause mortality, or MACE were observed primarily below eGFR 45 ml/min per 1.73 m², independent of urine albumin-creatinine ratio (uACR).

The use of older-age validated equations would substantially increase the prevalence of CKD but may not identify additional individuals at higher risk. These results suggest that current diagnostic thresholds may not be appropriate for older adults, particularly when applying older-age validated equations, and underscore the need to reconsider CKD definitions in the context of aging.