Temporal Evolution of the Impact of CKD on COVID-19 Outcomes: A Five-Year Nationwide Analysis

Background: CKD is among the strongest predictors of adverse COVID-19 outcomes, yet how CKD-associated risk evolved across pre-vaccination, roll-out, mass-vaccination, and post-pandemic phases remains incompletely defined in Latin America. Methods: We performed a nationwide retrospective analysis of Mexico’s historical surveillance open datasets, including all laboratory-confirmed cases from January 1, 2020 to June 30, 2025. The primary outcome was death among recorded cases (case-fatality); secondary outcomes were hospitalization, ICU admission, and invasive mechanical ventilation (IMV). Multivariable logistic models were fit overall, by age strata and year/pandemic phase, adjusting for demographics, comorbidities, and symptom-to-care interval; temporal patterns were summarized with LOESS and segmented interrupted time-series analysis. Sensitivity analyses included models restricted to ICU admissions and models additionally adjusted for municipal socioeconomic context. Results: Among 7,359,354 cases, 70,144 (1.0%) had CKD; crude case-fatality was 33% in CKD vs 4% without. In adjusted models, CKD was associated with higher case-fatality (aOR 1.20, 95% CI 1.19–1.20) and hospitalization (aOR 1.35, 95% CI 1.35–1.35), but not with ICU admission (aOR 0.98) or IMV (0.99). In the ICU-restricted cohort, CKD independently increased in-ICU case-fatality (aOR 1.38, 95% CI 1.25–1.51), strongest at ages 18–64 (aOR 1.52) and smaller at ≥65 (aOR 1.19). Year-specific models showed attenuation during mass vaccination (2022 aOR 1.13) followed by a resurgence in 2024 (aOR 1.90). LOESS/ITS revealed delayed and incomplete post-vaccination benefit for CKD with trend acceleration in 2023. Findings were robust after adding municipal SES indicators to adult models. Conclusions: Across five years of nationwide surveillance, CKD remained a dominant, independent correlate of COVID-19 case-fatality and hospitalization, with risk resurging in 2024. Lower ICU/IMV use yet higher in-ICU case-fatality among CKD patients may reflect selection effects and underscore the need for rapid escalation pathways.