Weight-adjusted waist index and all-cause and cardiovascular mortality in chronic kidney disease: A cohort study with mediation analysis of systemic inflammation.

The weight-adjusted waist index (WWI), a recently proposed marker reflecting central fat distribution independent of body weight, has emerged as a potential indicator of metabolic and cardiovascular risk. Considering the high burden of inflammation and metabolic disturbance in chronic kidney disease (CKD), we examined whether elevated WWI is associated with all-cause and cardiovascular disease (CVD) mortality among CKD patients and whether systemic inflammation, assessed by the neutrophil-to-lymphocyte ratio (NLR), mediates this relationship. Data were obtained from the National Health and Nutrition Examination Survey 1999 to 2018 cycles. WWI was calculated based on anthropometric measurements. Weighted multivariate Cox proportional hazards models were applied to examine the associations of WWI with mortality. Robustness was verified through WWI quartile-based survival curves and subgroup analyses. Mediation analysis was used to evaluate the indirect effect of NLR on the WWI-mortality relationship. A total of 5582 CKD participants were included. WWI levels were significantly and independently associated with increased risks of all-cause mortality (adjusted hazard ratio = 1.17, 95% confidence interval (CI): 1.09-1.26, P < .001) and CVD mortality (adjusted hazard ratio = 1.24, 95% CI: 1.09-1.41, P = .001). WWI showed a linear positive relationship with both outcomes (nonlinearity P > .05). Mediation analysis indicated that NLR exerted a modest but significant indirect effect on all-cause mortality (β = -9.94, 95% CI:-20.90--2.85, P < .001), explaining 6.66% of the total effect. Elevated WWI was independently associated with higher risks of all-cause and CVD mortality in CKD. NLR partially mediated these associations. Therefore, assessing both central adiposity and inflammatory burden may aid in identifying high-risk CKD patients and guide clinical strategies for improving long-term outcomes.