{"doi":"10.1016/j.kint.2022.06.022","title":"A randomized controlled pilot trial of anakinra for hemodialysis inflammation","abstract":"Chronic inflammation is highly prevalent among patients receiving maintenance hemodialysis and is associated with morbidity and mortality. Inhibiting inflammation with anti-cytokine therapy has been proposed but not well studied in this population. Therefore, we conducted the ACTION trial, a pilot, multicenter, randomized, placebo-controlled trial of an IL-1 receptor antagonist, anakinra, to evaluate safety, tolerability, and feasibility, and explore efficacy. Eighty hemodialysis patients with plasma concentrations of high sensitivity C-reactive protein (hsCRP) 2 mg/L and above were randomized 1:1 to placebo or anakinra 100 mg, three times per week via the hemodialysis circuit for 24 weeks, with an additional 24 weeks of post-treatment safety monitoring. Efficacy outcomes included changes in hsCRP (primary), cytokines, and patient-reported outcomes. Rates of serious adverse events and deaths were similar with anakinra and placebo (serious adverse events: 2.71 vs 2.74 events/patient-year; deaths: 0.12 vs 0.22 events/patient-year). The rate of adverse events of interest (including infections and cytopenias) was significantly lower with anakinra than placebo (0.48 vs 1.40 events/patient-year). Feasibility was demonstrated by attaining the enrollment target, a retention rate of 80%, and administration of 72% of doses. The median decrease in hsCRP from baseline to Week 24 was 41% in the anakinra group and 6% in the placebo group, a between-group difference that was not statistically significant. For IL-6, the median decreases were significant: 25% and 0% in the anakinra and placebo groups, respectively. An effect of anakinra on patient-reported outcomes was not evident. Thus, anakinra was well tolerated and did not increase infections or cytopenias. The promising safety data and potential efficacy on CRP and IL-6 provide support for conducting definitive trials of IL-1 inhibition to improve outcomes in hemodialysis patients. Chronic inflammation is highly prevalent among patients receiving maintenance hemodialysis and is associated with morbidity and mortality. Inhibiting inflammation with anti-cytokine therapy has been proposed but not well studied in this population. Therefore, we conducted the ACTION trial, a pilot, multicenter, randomized, placebo-controlled trial of an IL-1 receptor antagonist, anakinra, to evaluate safety, tolerability, and feasibility, and explore efficacy. Eighty hemodialysis patients with plasma concentrations of high sensitivity C-reactive protein (hsCRP) 2 mg/L and above were randomized 1:1 to placebo or anakinra 100 mg, three times per week via the hemodialysis circuit for 24 weeks, with an additional 24 weeks of post-treatment safety monitoring. Efficacy outcomes included changes in hsCRP (primary), cytokines, and patient-reported outcomes. Rates of serious adverse events and deaths were similar with anakinra and placebo (serious adverse events: 2.71 vs 2.74 events/patient-year; deaths: 0.12 vs 0.22 events/patient-year). The rate of adverse events of interest (including infections and cytopenias) was significantly lower with anakinra than placebo (0.48 vs 1.40 events/patient-year). Feasibility was demonstrated by attaining the enrollment target, a retention rate of 80%, and administration of 72% of doses. The median decrease in hsCRP from baseline to Week 24 was 41% in the anakinra group and 6% in the placebo group, a between-group difference that was not statistically significant. For IL-6, the median decreases were significant: 25% and 0% in the anakinra and placebo groups, respectively. An effect of anakinra on patient-reported outcomes was not evident. Thus, anakinra was well tolerated and did not increase infections or cytopenias. The promising safety data and potential efficacy on CRP and IL-6 provide support for conducting definitive trials of IL-1 inhibition to improve outcomes in hemodialysis patients. The mortality rate for patients undergoing maintenance hemodialysis is unacceptably high wit","journal":"Kidney International","year":2022,"id":251972,"datarank":0.48283137373023016,"base_score":3.2188758248682006,"endowment":3.2188758248682006,"self_citation_contribution":0.48283137373023016,"citation_network_contribution":0.0,"self_endowment_contribution":0.48283137373023016,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9526,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":11400,"name":"Adriana M. Hung","orcid":"0000-0002-3203-1608","position":1,"is_corresponding":false},{"id":108986,"name":"Rajnish Mehrotra","orcid":"0000-0003-2833-067X","position":2,"is_corresponding":false},{"id":337715,"name":"Jesse Y. Hsu","orcid":"0000-0002-1522-6534","position":3,"is_corresponding":false},{"id":292967,"name":"Dominic S. Raj","orcid":"0000-0001-9647-083X","position":4,"is_corresponding":false},{"id":225665,"name":"David M. Charytan","orcid":"0000-0002-7695-3583","position":5,"is_corresponding":false},{"id":463302,"name":"Finnian R. Mc Causland","orcid":"0000-0002-0299-0533","position":6,"is_corresponding":false},{"id":520753,"name":"Renu Regunathan-Shenk","orcid":"0000-0003-4407-9067","position":7,"is_corresponding":false},{"id":35350,"name":"J. Richard Landis","orcid":"0000-0001-8099-0988","position":8,"is_corresponding":false},{"id":214519,"name":"Paul L. Kimmel","orcid":null,"position":9,"is_corresponding":false},{"id":528585,"name":"Alan S. Kliger","orcid":"0000-0002-9103-477X","position":10,"is_corresponding":false},{"id":54241,"name":"Jonathan Himmelfarb","orcid":"0000-0002-3319-1224","position":11,"is_corresponding":false},{"id":249667,"name":"T. Alp İkizler","orcid":"0000-0002-5717-4218","position":12,"is_corresponding":false},{"id":277168,"name":"Laura M. Dember","orcid":"0000-0002-9735-7473","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T00:24:46.226372Z","pmid":"35863559","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}