Evolving Trends and Disparities in Chronic Kidney Disease and Sepsis-Related Mortality in the United States from 1999 to 2023

Background: Chronic kidney disease (CKD) predisposes patients to infections, and when sepsis occurs concurrently, outcomes are particularly severe. Despite this clinical importance, nationwide mortality trends for CKD–sepsis have not been comprehensively evaluated. Methods: We extracted Multiple Cause of Death data from the CDC WONDER database to analyze age-adjusted mortality rates (AAMRs) for sepsis-related deaths among patients with CKD in the United States from 1999 to 2023. Subgroup analyses were conducted by age, sex, race/ethnicity, and urban–rural status and mortality trends were assessed across the study period. Results: CKD–sepsis mortality increased steadily over the 25-year period with AAMR increasing from 4.53 per 100,000 in 1999 to 5.59 per 100,000 in 2023 (APC: 0.88*; 95% CI: 0.26 to 1.52; p = 0.0078). Men exhibited higher mortality than women. Race-stratified analysis revealed declining mortality among non-Hispanic Black, Hispanic, and American Indian/Alaska Native populations, while non-Hispanic White individuals experienced a notable rise. Mortality also significantly rose in the rural population compared to urban population. Conclusion: Mortality from CKD–sepsis has escalated steadily in the United States, with notable disparities across demographic groups. The rise amongst White and rural populations highlights the intersection of chronic illness, structural healthcare barriers, and potential impacts of the opioid crisis. Addressing these disparities will require targeted preventive strategies, improved infection control, and equitable access to nephrology and critical care services.