Patients with chronic kidney disease (CKD) are particularly vulnerable to complications from influenza. A prespecified subgroup analysis of the DANFLU-2 trial has found that a high-dose inactivated influenza vaccine (HD-IIV) provides a greater relative benefit against severe clinical outcomes compared to a standard-dose vaccine (SD-IIV) in this high-risk population.¹

Methodology

DANFLU-2 was a large, pragmatic, open-label, individually randomised trial conducted in Denmark over three influenza seasons (2022–2025). The trial aimed to assess the relative effectiveness of HD-IIV versus SD-IIV in the general population aged 65 years and older.²

This analysis focused on a cohort of 332,438 participants, of whom 46,788 (14.1%) had CKD at baseline. Participants were randomised to receive either HD-IIV or SD-IIV. The primary endpoint was hospitalisation for influenza or pneumonia. Secondary endpoints included hospitalisation for any cardiorespiratory disease, all-cause hospitalisation, and all-cause mortality.

Results

The study found that the effectiveness of the vaccine differed significantly based on kidney function. For the primary endpoint of hospitalisation for influenza or pneumonia, the relative vaccine effectiveness (rVE) of HD-IIV versus SD-IIV was 16.9% (95% CI: 3.4%–28.5%) in participants with CKD. This was in contrast to an rVE of just 0.6% (95% CI: -9.6% to 9.9%) in those without CKD (p for interaction=0.046).

This corresponds to an absolute risk reduction of 0.29% in the CKD group, with a number needed to treat (NNT) of 359 to prevent one additional hospitalisation.

The benefit was even more pronounced for influenza-specific hospitalisations. In the CKD group, the rVE was 68.6% (95% CI: 46.7%–82.3%; NNT=561), compared to 30.6% (95% CI: 7.2%–48.2%) in the non-CKD group (p for interaction=0.0079).

Reductions in hospitalisations for cardiorespiratory disease, cardiovascular disease, and heart failure were consistent across both groups, irrespective of CKD status.

In Practice/Interpretation

This analysis from the DANFLU-2 trial provides important evidence for vaccination strategy in a vulnerable patient group. The authors concluded, "we observed a benefit of HD-IIV vs SD-IIV against hospitalization for influenza or pneumonia, as well as hospitalization for influenza, with suggestion of a greater relative benefit amongst those with CKD."¹ The findings support the consideration of HD-IIV to maximise protection against severe influenza-related complications in individuals with chronic kidney disease.

This study was funded by Sanofi.

References

1. Bartholdy KV, Johansen ND, Modin D, et al. High-Dose vs Standard-Dose Influenza Vaccine in Chronic Kidney Disease: The DANFLU-2 Trial Subgroup Analysis. JACC. 2025;86(25):2636-2647. https://doi.org/10.1016/j.jacc.2025.10.005.

2. Johansen ND, Modin D, Loiacono MM, et al. High-dose influenza vaccine effectiveness against hospitalization in older adults. N Engl J Med. 2025. https://doi.org/10.1056/NEJMoa2509907.

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