The Obesity Paradox in Chronic Kidney Disease: Cardiorespiratory Fitness Is Associated With Mortality Independent of Body Mass Index

Rationale & Objective The obesity paradox, where higher body mass index (BMI) is associated with better survival, has been observed in chronic disease populations. However, the interaction between BMI, cardiorespiratory fitness (CRF), and mortality in CKD remains incompletely understood. We examined the association between BMI, age-adjusted CRF, and all-cause mortality in a large CKD cohort. Study Design Retrospective cohort study. Setting & Participants 13,521 predominantly male US Veterans (97.4% male) with CKD from the Exercise Testing and Health Outcomes Study (ETHOS) within the Veterans Affairs healthcare system. Predictors BMI categories (normal weight <25.0, overweight 25.0-29.9, and obese ≥30.0 kg/m 2 ) and age-adjusted CRF quartiles based on metabolic equivalents (METs) achieved during maximal exercise tolerance testing using Bruce protocol. The index date was the date of exercise testing. Outcome All-cause mortality. Analytical Approach Cox proportional hazards models adjusted for age, sex, diabetes mellitus, hypertension, and cardiovascular disease assessed mortality risk across BMI-fitness combinations, with normal BMI and least fit as reference. Results During a mean follow-up of 7.4 years, 5,144 deaths (38.0%) occurred. Higher BMI was associated with lower mortality risk: overweight (HR 0.82, 95% CI 0.70-0.95) and obese (HR 0.71, 95% CI 0.61-0.82) versus normal BMI. Higher CRF was associated with progressively lower mortality: moderate fit (HR 0.61, 95% CI 0.50-0.74) and most fit (HR 0.49, 95% CI 0.40-0.60) versus least fit. The combination of obese BMI and highest fitness was associated with 64% lower mortality risk (HR 0.36, 95% CI 0.25-0.51). Limitations Predominantly male Veteran population; single baseline BMI and fitness measurements; observational design precludes causal inference. Conclusions In this predominantly male Veteran CKD cohort, higher BMI was associated with lower all-cause mortality across all fitness levels. Age-adjusted CRF demonstrated a strong, graded inverse association with mortality independent of BMI. These observational findings support integrating fitness assessment into CKD management.