Tooth loss elevates all-cause and cause-specific mortality in adults with chronic kidney disease: The mediating role of frailty

Chronic kidney disease (CKD) patients experience a high oral disease burden and mortality. We evaluated whether loss of natural teeth predicts all-cause and cause-specific mortality in adults with CKD and whether a Frailty Index (FI) mediates this association. We analyzed 12,639 adults with CKD from the National Health and Nutrition Examination Survey 1999-2018. Tooth counts (third molars excluded) were grouped clinically. A 53-item FI was constructed. Survey-weighted Cox models with sensitivity checks, restricted cubic splines, piecewise Cox regression, and counterfactual mediation analysis were applied. Sequential models added FI and then ln(hs-CRP) to examine attenuation. Prespecified subgroup and sensitivity analyses were conducted, including cycles with prosthetic information. Greater tooth loss was independently associated with higher all-cause, cardiovascular, and cancer mortality. In fully adjusted models, compared with complete dentition, adjusted hazard ratios (HRs; 95% confidence intervals) for all-cause mortality were as follows: tooth loss, 1.53 (1.24-1.88); lacking functional, 1.93 (1.54-2.42); severe tooth loss, 1.99 (1.54-2.57); and edentulism, 2.16 (1.75-2.67). Spline analyses supported nonlinearity for all-cause, cardiovascular, and cancer mortality; segmented models were consistent with a steeper slope at lower tooth counts and a plateau thereafter. Piecewise analysis identified a threshold at 3 missing teeth: below the threshold, each additional missing tooth had an HR of 1.161 (1.108-1.216); above the threshold, HR was 1.010 (1.006-1.014) (log-rank P < .001). Associations were broadly consistent across sex and CKD risk strata, with relative effects attenuating at higher Kidney Disease: Improving Global Outcomes risk categories, where baseline hazards were greater. In cycles with prosthetic data, associations were weaker among participants receiving dental prosthetic rehabilitation. FI mediated 29.42% of the effect on all-cause mortality. Sequential adjustment indicated additional, smaller attenuation after ln(hs-CRP), while the primary associations remained significant. In US adults with CKD, tooth loss predicts higher mortality; frailty explains ~30% of this association, suggesting that the integration of routine oral health screening and dental interventions with frailty assessment and multidisciplinary care (nutritional support, rehabilitation, and psychosocial services) may identify at-risk CKD patients and offer modifiable targets to improve survival and quality of life.