Abstract
Background: Chronic periodontal disease (CPD) may contribute to systemic inflammation and adverse outcomes in patients undergoing maintenance hemodialysis, but age-specific risks remain unclear. We aimed to evaluate the association between CPD and clinical outcomes in hemodialysis patients, stratified by age. Methods: We conducted a retrospective cohort study using the TriNetX Research Network. Adults aged 45-64 or ≥65 years initiating maintenance hemodialysis were included. CPD exposure was defined using ICD-10-CM codes documented within 6 months before or up to 5 years after hemodialysis initiation. Outcomes included all-cause mortality, pneumonia, fracture, and major adverse cardiovascular events (MACE) over a 5-year follow-up period. Propensity score matching was conducted within each age group using a comprehensive model that included age, sex, race, comorbidities, medications, and laboratory values. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated using Cox models. Subgroup and sensitivity analyses were conducted to assess robustness and effect modification. Results: CPD was significantly associated with increased risks of all-cause mortality in both younger (aHR = 1.313, 95% CI: 1.129-1.527; p<0.001) and older patients (aHR = 1.126, 95% CI: 1.048-1.209; p=0.001), with stronger associations in the younger group. Subgroup analysis showed elevated mortality risks in younger males, females, and non-diabetic individuals. Pneumonia risk was significantly increased across both age groups, with particularly high risks in younger females and older males. CPD was also associated with a higher risk of fracture, particularly among older adults (aHR = 1.673, 95% CI: 1.375-2.036; p<0.001), with consistent findings across subgroups. No significant associations were observed between CPD and MACE in either age stratum. Sensitivity analyses adjusting for comorbidities and inflammatory markers supported the primary findings. Conclusion: CPD is associated with increased risks of mortality, pneumonia, and fractures among hemodialysis patients, with variation by age and clinical subgroup. These findings support integrating periodontal screening and preventive strategies into hemodialysis care. Younger patients may benefit from early intervention to reduce infection and mortality risk, while older adults may require targeted skeletal protection.