{"doi":"10.1016/j.jacc.2025.10.005","title":"High-Dose vs Standard-Dose Influenza Vaccine in Chronic Kidney Disease","abstract":"<h4>Background</h4>Influenza-related complications occur frequently in persons with chronic kidney disease (CKD). Limited data exist on the effectiveness of high-dose inactivated influenza vaccine (HD-IIV) in persons with CKD.<h4>Objectives</h4>The purpose of this study was to assess the relative effectiveness (rVE) of HD-IIV vs standard-dose inactivated influenza vaccine (SD-IIV) against severe clinical outcomes in persons with CKD from the elderly general population.<h4>Methods</h4>DANFLU-2 (A Pragmatic Randomized Trial to Evaluate the Effectiveness of High-Dose Influenza Vaccine vs. Standard-Dose Influenza Vaccine in Older Adults) was a pragmatic, open-label, individually randomized trial conducted in Denmark during the 2022-2023, 2023-2024, and 2024-2025 influenza seasons with the aim of assessing the rVE of HD-IIV vs SD-IIV in an older adult general population. In this prespecified secondary analysis, we assessed the rVE against severe clinical outcomes according to the presence of CKD. CKD was defined using data from laboratory registries and International Classification of Diseases-10th Revision diagnosis codes 10 years before vaccination.<h4>Results</h4>Among 332,438 DANFLU-2 participants (mean age 73.7 ± 5.8 years; 48.6% women), 46,788 (14.1%) had CKD at baseline. The effect of HD-IIV vs SD-IIV on hospitalization for influenza or pneumonia differed by CKD status: rVE was 16.9% (95% CI: 3.4%-28.5%) in participants with CKD vs 0.6% (95% CI: -9.6% to 9.9%) in those without CKD (P interaction = 0.046). Absolute risks for hospitalization for influenza or pneumonia were 1.7% with SD-IIV vs 1.3% with HD-IIV in CKD, corresponding to an absolute risk reduction of -0.29% (95% CI: -0.50% to 0.058%; number needed to treat [NNT] = 359). For influenza hospitalizations specifically, the benefit of HD-IIV was also substantially greater in CKD: rVE 68.6% (95% CI: 46.7%-82.3%; NNT = 561) vs 30.6% (95% CI: 7.2%-48.2%; NNT =3,953) in non-CKD (P interaction = 0.0079). Reductions in hospitalizations for cardiorespiratory disease, cardiovascular disease, heart failure, and laboratory-confirmed influenza were consistent regardless of CKD (all P interaction > 0.05).<h4>Conclusions</h4>In this prespecified analysis of DANFLU-2, including the largest CKD population ever in an individually randomized vaccine trial, 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 among those with CKD. Furthermore, the beneficial effect of HD-IIV vs SD-IIV on multiple cardiorespiratory outcomes was consistent across participants irrespective of CKD status.","journal":"JACC","year":2025,"id":6319,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0382,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-12-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":27949,"name":"Niklas Dyrby Johansen","orcid":"0000-0001-6959-3236","position":1,"is_corresponding":false},{"id":27950,"name":"Daniel Modin","orcid":"0000-0002-7566-0519","position":2,"is_corresponding":false},{"id":27953,"name":"Matthew M. 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