: Publication 16714

Publication 16714

Title:	Association of Influenza Vaccination With Acute Kidney Injury: A Prospective Target Trial Emulation Study
Journal:	American Journal of Kidney Diseases
Published:	17 Oct 2025
Pubmed:	https://pubmed.ncbi.nlm.nih.gov/41110628/
DOI:	https://doi.org/10.1053/j.ajkd.2025.09.005

Abstract

RATIONALE & OBJECTIVE: The impact of influenza vaccination on the risk of acute kidney injury (AKI) has not been thoroughly evaluated in large-scale prospective studies. We assessed whether influenza vaccination was associated with a reduced incidence of AKI among individuals aged 65 years or older.

STUDY DESIGN: Target trial emulated with a sequential trial design.

SETTING & PARTICIPANTS: Participants aged 65 years or older in the UK Biobank.

EXPOSURE: Influenza vaccination compared with no influenza vaccine.

OUTCOME: Incident AKI during 1 year after vaccination. Participants were followed from baseline until the diagnosis of AKI, death, loss to follow-up, or for 1 year after entering the study, whichever occurred first.

ANALYTICAL APPROACH: Fifty trials were emulated, each with a 1-month enrollment period. These trials began in September 2007 and continued from September to January of the following year until January 2017. Eligible participants could be included in multiple trials until they no longer met the inclusion criteria. Propensity score matching was applied to match vaccine recipients to unvaccinated individuals in a 1:1 ratio to control for confounders, emulating random assignment. A clustered marginal competing risk model that accounts for the within-pair clustering of outcomes was fit to estimate the hazard ratio, along with the 95% confidence interval, characterizing the association between the use of influenza vaccination and incident AKI.

RESULTS: Overall, the cohort included 1,408,922 eligible person-trials in the general practice data. After propensity score matching, 97,663 pairs of person-trials were included. During the 1-year follow-up, a total of 598 incident AKI events were observed. In the primary analysis, the incidence of AKI was 36.8 per 10,000 person-years (PYs) in unvaccinated participants and 30.6 per 10,000 PYs in the vaccinated group. After adjusting for potential confounders using propensity score matching, influenza vaccination was associated with a 17% lower AKI risk (HR, 0.83 [95% CI, 0.71-0.98]). The cumulative mortality rates were 62.8 per 10,000 PYs in the unvaccinated group and 47.2 per 10,000 PYs in the vaccinated group, corresponding to an HR of 0.75 (95% CI, 0.66-0.85). These findings remained consistent in subgroup and sensitivity analyses.

LIMITATIONS: Potential residual confounding from variations in vaccine formulations and batch; potential selection bias from restricting to participants with linked primary care data in the UK Biobank; and potential outcome misclassification from use of a code-based algorithm to identify AKI.

CONCLUSIONS: In this prospective population-based study of older adults within the UK Biobank, influenza vaccination was significantly associated with a lower risk of incident AKI. These findings support use of influenza vaccination in older adults to reduce influenza and its kidney-related complications.

PLAIN-LANGUAGE SUMMARY: Influenza infection can damage multiple systems beyond the respiratory system and cause impairment of kidney function. We hypothesized that influenza vaccination may provide a more extensive protective effect beyond respiratory diseases. However, the impact of influenza vaccination on the risk of acute kidney injury (AKI) has not been sufficiently evaluated. This study investigated the association between influenza vaccination and AKI in older adults represented in the UK Biobank, a large prospective cohort. By emulating a targeted randomized clinical trial in this cohort, we found that influenza vaccination may reduce the risk of AKI by 17%. This effect was partially mediated by a reduction in influenza and pneumonia. These findings support the broader implementation of influenza vaccination to reduce both influenza and kidney-related complications in older adult populations.

Abstract

7 Authors