{"doi":"10.1093/ckj/sfaf108","title":"Targeting IL-6 in antibody-mediated kidney transplant rejection","abstract":"<jats:title>ABSTRACT</jats:title>\n               <jats:p>Interleukin (IL)-6 is a major pro-inflammatory cytokine and central regulator of innate and adaptive immune responses. Clinical trials testing antibodies against IL-6 or its receptors have demonstrated its involvement in the pathogenesis of several autoimmune and inflammatory disorders and in the systemic inflammation and anemia associated to kidney failure and also in kidney allograft rejection. Additionally, the anti-IL-6 receptor antibody tocilizumab and the anti-IL-6 antibody clazakizumab have been studied for the treatment of naïve as well as resistant antibody-mediated kidney allograft rejection with mixed results in observational studies and early clinical development. Following promising results with a clazakizumab in a phase 2 placebo-controlled trial, a large phase 3 trial (IMAGINE) was terminated in 2024 for futility at interim analysis. Investigator-initiated clinical development continues in a smaller phase 3 trial testing tocilizumab (INTERCEPT). In this viewpoint article, we evaluate the pathophysiology of IL-6 in antibody-mediated kidney allograft rejection along with the current status of the clinical development of IL-6 targeting therapies for antibody-mediated kidney allograft rejection episodes within the wider frame of IL-6 targeting therapies in kidney failure that are considered the major causes of graft loss in kidney transplantation.</jats:p>","journal":"Clinical Kidney Journal","year":2025,"id":640584,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1664916,"name":"Berk Mizrak","orcid":null,"position":1,"is_corresponding":false},{"id":1080210,"name":"Sidar Copur","orcid":null,"position":2,"is_corresponding":false},{"id":1664917,"name":"Ezgi N Alper","orcid":null,"position":3,"is_corresponding":false},{"id":1664918,"name":"Sebahat Akgul","orcid":null,"position":4,"is_corresponding":false},{"id":23179,"name":"Alberto Ortíz","orcid":"0000-0002-9805-9523","position":5,"is_corresponding":false},{"id":1664919,"name":"Caner Susal","orcid":null,"position":6,"is_corresponding":false},{"id":282740,"name":"Mehmet Kanbay","orcid":"0000-0002-1297-0675","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Targeting IL-6 in antibody-mediated kidney transplant rejection","abstract":"<jats:title>ABSTRACT</jats:title>\n               <jats:p>Interleukin (IL)-6 is a major pro-inflammatory cytokine and central regulator of innate and adaptive immune responses. Clinical trials testing antibodies against IL-6 or its receptors have demonstrated its involvement in the pathogenesis of several autoimmune and inflammatory disorders and in the systemic inflammation and anemia associated to kidney failure and also in kidney allograft rejection. Additionally, the anti-IL-6 receptor antibody tocilizumab and the anti-IL-6 antibody clazakizumab have been studied for the treatment of naïve as well as resistant antibody-mediated kidney allograft rejection with mixed results in observational studies and early clinical development. Following promising results with a clazakizumab in a phase 2 placebo-controlled trial, a large phase 3 trial (IMAGINE) was terminated in 2024 for futility at interim analysis. Investigator-initiated clinical development continues in a smaller phase 3 trial testing tocilizumab (INTERCEPT). In this viewpoint article, we evaluate the pathophysiology of IL-6 in antibody-mediated kidney allograft rejection along with the current status of the clinical development of IL-6 targeting therapies for antibody-mediated kidney allograft rejection episodes within the wider frame of IL-6 targeting therapies in kidney failure that are considered the major causes of graft loss in kidney transplantation.</jats:p>","is_dataset_classified":null,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40357502","pmcid":"PMC12067060","openalex_id":"https://openalex.org/W4410348213","authors":[],"funders":[{"funder_name":"European Union","grant_id":"952512","title":"Koç University Transplant Immunology Research Center of Excellence"},{"funder_name":"KUTTAM","grant_id":"","title":null}],"total_grants":2,"fwci":7.3227,"citation_percentile":0.97385223,"influential_citations":0,"citation_trend":[{"year":2025,"count":2},{"year":2026,"count":5}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://academic.oup.com/ckj/article-pdf/18/5/sfaf108/62934271/sfaf108.pdf","host_type":"journal"},{"url":"https://academic.oup.com/ckj/article-pdf/18/5/sfaf108/62934271/sfaf108.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/ckj/advance-article-pdf/doi/10.1093/ckj/sfaf108/62934271/sfaf108.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/ckj/sfaf108","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40357502","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12067060","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12067060","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12067060?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1093/ckj/sfaf108","host_type":""},{"url":"https://hdl.handle.net/10486/773580","host_type":""}],"fields_of_study":["Renal Transplantation Outcomes and Treatments","Transplantation: Methods and Outcomes","Organ Transplantation Techniques and Outcomes","03 medical and health sciences","0302 clinical medicine"],"mesh_terms":[],"keywords":["Kidney transplant","Antibody","Donor specific antibodies","Medicine","Kidney transplantation","Kidney","Immunology","Biology","Internal medicine","Interleukin 6","Tocilizumab","Canakinumab","Antibody-mediated Rejection","Medicina","CKJ Review"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"},{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-07T12:53:41.945971Z","pmid":null,"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":[]}