Association of Life’s Essential 8 with Risk of End-Stage Kidney Disease in the United Kingdom Biobank Study

BACKGROUND: Life's Essential 8 (LE8) is a comprehensive cardiovascular health (CVH) metric integrating eight behavioral and biological factors and has been associated with cardiovascular disease risk. However, evidence linking LE8 to end-stage kidney disease (ESKD) is lacking. METHODS: We analyzed the United Kingdom (UK) Biobank data prospectively on participants who were free of ESKD at baseline. The LE8 score, calculated as the unweighted average of eight components (range, 0-100), was categorized as low (0-49), moderate (50-79), and high (80-100), with higher scores indicating more favorable health status. The primary outcome was incident ESKD, defined as needing kidney replacement therapy or reaching CKD stage G5. We used Cox proportional hazards models to estimate hazard ratios (HR) for incident ESKD, separately for LE8 categories and for continuous LE8 scores, with nonlinear associations assessed using restricted cubic splines (RCS). We also estimated population-attributable fractions (PAFs) for non-optimal LE8 and its subscales and components. RESULTS: Among 276,494 participants (mean [SD] age 56 [8] years; 48% male; 95% White), 455 incident ESKD events occurred over a median follow-up of 14.1 years. In fully adjusted Cox models, each 10-point decrement in LE8 score was associated with higher ESKD risk (HR, 1.47; 95% CI, 1.34-1.60). Compared with high LE8, moderate LE8 was associated with a 2.1-fold higher risk of incident ESKD (HR, 2.11; 95% CI, 1.39-3.21), and low LE8 was associated with a more than five-fold higher risk (HR, 5.57; 95% CI, 3.42-9.07). Subscale analyses showed similar patterns. RCS analysis suggested nonlinear associations for overall LE8 and the biological subscale, with steeper risk gradients at lower scores. Blood pressure, blood glucose, physical activity, and smoking had statistically significant estimated PAF for incident ESKD, with the largest fractions observed for blood pressure and blood glucose. CONCLUSIONS: In this large prospective cohort, low LE8 was associated with a substantially higher risk of incident ESKD. These findings highlight the potential relevance of LE8-guided improvement in behavioral and biological factors for ESKD prevention.