{"doi":"10.3389/ti.2023.11367","title":"A Multi-Modal Approach to Islet and Pancreas Transplantation With Calcineurin-Sparing Immunosuppression Maintains Long-Term Insulin Independence in Patients With Type I Diabetes","abstract":"Long-term success in beta-cell replacement remains limited by the toxic effects of calcineurin inhibitors (CNI) on beta-cells and renal function. We report a multi-modal approach including islet and pancreas-after-islet (PAI) transplant utilizing calcineurin-sparing immunosuppression. Ten consecutive non-uremic patients with Type 1 diabetes underwent islet transplant with immunosuppression based on belatacept (BELA; n = 5) or efalizumab (EFA; n = 5). Following islet failure, patients were considered for repeat islet infusion and/or PAI transplant. 70% of patients (four EFA, three BELA) maintained insulin independence at 10 years post-islet transplant, including four patients receiving a single islet infusion and three patients undergoing PAI transplant. 60% remain insulin independent at mean follow-up of 13.3 ± 1.1 years, including one patient 9 years after discontinuing all immunosuppression for adverse events, suggesting operational tolerance. All patients who underwent repeat islet transplant experienced graft failure. Overall, patients demonstrated preserved renal function, with a mild decrease in GFR from 76.5 ± 23.1 mL/min to 50.2 ± 27.1 mL/min ( p = 0.192). Patients undergoing PAI showed the greatest degree of renal impairment following initiation of CNI (56% ± 18.7% decrease in GFR). In our series, repeat islet transplant is ineffective at maintaining long-term insulin independence. PAI results in durable insulin independence but is associated with impaired renal function secondary to CNI dependence.","journal":"Transplant International","year":2023,"id":357867,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":725143,"name":"Andrew M. Posselt","orcid":null,"position":1,"is_corresponding":false},{"id":485076,"name":"Gregory L. Szot","orcid":"0000-0002-3921-049X","position":2,"is_corresponding":false},{"id":1107646,"name":"Miguel Nunez","orcid":"0000-0003-0354-5359","position":3,"is_corresponding":false},{"id":390649,"name":"Keli S. Santos-Parker","orcid":"0000-0002-2773-9775","position":4,"is_corresponding":false},{"id":73995,"name":"James M. Gardner","orcid":"0000-0003-3470-9520","position":5,"is_corresponding":false},{"id":1108013,"name":"Giulia Worner","orcid":null,"position":6,"is_corresponding":false},{"id":452819,"name":"Garrett R. Roll","orcid":"0000-0001-6241-7037","position":7,"is_corresponding":false},{"id":687731,"name":"Shareef Syed","orcid":"0000-0002-1475-778X","position":8,"is_corresponding":false},{"id":949221,"name":"Yvonne Kelly","orcid":"0000-0002-1494-0429","position":9,"is_corresponding":false},{"id":727003,"name":"Casey Ward","orcid":"0000-0001-6344-2971","position":10,"is_corresponding":false},{"id":1108014,"name":"Medhi Tavakol","orcid":null,"position":11,"is_corresponding":false},{"id":566542,"name":"Kristina Johnson","orcid":null,"position":12,"is_corresponding":false},{"id":29200,"name":"Umesh Masharani","orcid":"0000-0002-3269-804X","position":13,"is_corresponding":false},{"id":351269,"name":"Peter G. Stock","orcid":"0000-0002-5806-0167","position":14,"is_corresponding":false},{"id":1036823,"name":"Steven A. Wisel","orcid":"0000-0002-4571-2517","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-19T01:13:39.186262Z","pmid":"37359825","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":[]}