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Am J Kidney Dis
. 2025 Oct 17:S0272-6386(25)01078-9.
doi: 10.1053/j.ajkd.2025.09.005. Online ahead of print. Association of Influenza Vaccination With Acute Kidney Injury: A Prospective Target Trial Emulation Study
Lin Zhuo 1 , Baixue Zhang 2 , Yi Huang 3 , Qiaorui Wen 4 , Shengfeng Wang 5 , Siyan Zhan 6 , Houyu Zhao 7
Affiliations
Rationale & objective: The impact of influenza vaccination (FluVac) on the risk of acute kidney injury (AKI) has not been thoroughly evaluated in large-scale prospective studies. We aimed to assess whether FluVac is 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 (FluVac) compared with no FluVac.
Outcome: Incident AKI during one year after vaccination. Participants were followed from baseline until the diagnosis of AKI, death, loss to follow-up, or for one year after entering the study, whichever occurred first.
Analytical approach: Fifty trials were emulated, each with a one-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 (HR), along with the 95% confidence interval (CI), characterizing the association between the use of FluVac 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 one-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, FluVac 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, FluVac 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.
Keywords: Acute kidney injury; Influenza vaccination; Prospective cohort; Target trial emulation; UK Biobank.
. 2025 Oct 17:S0272-6386(25)01078-9.
doi: 10.1053/j.ajkd.2025.09.005. Online ahead of print. Association of Influenza Vaccination With Acute Kidney Injury: A Prospective Target Trial Emulation Study
Lin Zhuo 1 , Baixue Zhang 2 , Yi Huang 3 , Qiaorui Wen 4 , Shengfeng Wang 5 , Siyan Zhan 6 , Houyu Zhao 7
Affiliations
- PMID: 41110628
- DOI: 10.1053/j.ajkd.2025.09.005
Rationale & objective: The impact of influenza vaccination (FluVac) on the risk of acute kidney injury (AKI) has not been thoroughly evaluated in large-scale prospective studies. We aimed to assess whether FluVac is 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 (FluVac) compared with no FluVac.
Outcome: Incident AKI during one year after vaccination. Participants were followed from baseline until the diagnosis of AKI, death, loss to follow-up, or for one year after entering the study, whichever occurred first.
Analytical approach: Fifty trials were emulated, each with a one-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 (HR), along with the 95% confidence interval (CI), characterizing the association between the use of FluVac 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 one-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, FluVac 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, FluVac 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.
Keywords: Acute kidney injury; Influenza vaccination; Prospective cohort; Target trial emulation; UK Biobank.