Glomerular hyperfiltration as an independent predictor of all-cause mortality in healthy adults: A nationally representative cohort study

Introduction: Glomerular hyperfiltration (GHF) is a marker of systemic dysfunction, but its link to long-term mortality in healthy adults remains unclear. Methods: This nationally representative cohort study included 14,309 healthy adults from the National Health and Nutrition Examination Survey. GHF was defined as age- and sex-specific estimated glomerular filtration rate (eGFR) indexed for individual body surface area (BSA) exceeding the 95th percentile. Normal filtration was defined as the 25th-75th percentile. All-cause mortality risk was assessed using Cox proportional hazards models, propensity score matching, and restricted cubic spline regression. Results: Among participants, 722 exhibited GHF (median eGFR: 168 mL/min/BSA m²) and 7,153 had normal filtration (median eGFR: 115 mL/min/BSA m²). Over a median follow-up of 123 months, GHF was associated with increased mortality risk (fully adjusted HR: 1.86; 95% CI: 1.33, 2.60). Propensity score-matched analysis yielded consistent results (HR: 2.60; 95% CI: 1.25, 5.39). Restricted cubic splines revealed a U-shaped eGFR-mortality relationship, with risk progressively increasing above the 60th eGFR percentile. Sensitivity analyses confirmed the robustness of these findings across various stratification methods and exclusion criteria. Conclusions: GHF independently predicts increased mortality in healthy adults, suggesting its potential role as a systemic risk marker and highlighting the potential value of revisiting kidney health assessment frameworks.