Long-term Outcomes With Islet-Alone and Islet-After-Kidney Transplantation for Type 1 Diabetes in the Clinical Islet Transplantation Consortium: The CIT-08 Study
Authors: Rickels Michael R. , Eggerman Thomas L. , Bayman Levent , Qidwai Julie C. , Alejandro Rodolfo , Bridges Nancy D. , Hering Bernhard J. , Markmann James F. , Senior Peter A. , Hunsicker Lawrence G. ,   on behalf of the Clinical Islet Transplantation Consortium, Avila Jose , Begley Beth , Cano Jose , Carpentier Sallie , Holbrook Elizabeth , Hutchinson Jennifer , Larsen Christian P. , Moreno Johanna , Sears Marti , Turgeon Nicole A. , Webster Dasia , Berne Christian , Jorns Carl , Lundgren Torbjörn , Rydén Mikael , Cagliero Enrico , Crisalli Kerry , Deng S. , Lei Ji , Markmann James F. , Nathan David , Al-Saden Patrice , Battle Jason , Chen Xioajuan , Hecyk Angela , Kaufman Dixon B. , Kissler Herman , Luo Xunrong , Molitch Mark , Monson Natalie , Stuart Elyse , Wallia Amisha , Wang Lingjia , Wang Shusen , Zhang Xiaomin , Bridges Nancy D. , Czarniecki Christine W. , Goldstein Julia S. , Granderson Tomeka , Morrison Yvonne , Priore Allison , Putz Gerry , Robien Mark A. , Schneider Elizabeth , Arreaza Guillermo , Eggerman Thomas L. , Green Neal , Bigam David L. , Campbell Patricia , Dinyari Parastoo , Imes Sharleen , Kin Tatsuya , Kneteman Norman M. , Koh Angela , Lyon James , Malcolm Andrew , O’Gorman Doug , Onderka Chris , Owen Richard , Pawlick Rena , Richer Brad , Rosichuk Shawn , Ryan Edmond A. , Sarman Donna , Schroeder Adam , Senior Peter A. , Shapiro A.M. James , Toth Lana , Toth Vali , Zhai Wendy , Johnson Kristina , McElroy Joan , Posselt Andrew M. , Ramos Marissa , Rojas Tara , Stock Peter G. , Szot Gregory , Barbaro Barbara , George Leelama , Martellotto Joan , Oberholzer Jose , Qi Meirigeng , Wang Yong , Bayman Levent , Chaloner Kathryn , Clarke William R. , Dillon Joseph S. , Diltz Cynthia , Doelle Gregory C. , Ecklund Dixie , Ernst Holly , Feddersen Deb , Foster Eric , Hunsicker Lawrence G. , Jasperson Carol , Lafontant David-Erick , McElvany Karen , Neill-Hudson Tina , Nollen Deb , Qidwai Julie , Schwieger Traci , Shields Beth , Willits Jamie , Yankey Jon , Alejandro Rodolfo , Alvarez A. , Curry Corrales Andrea , Faradji Raquel , Froud Tatiana , Alvarez Gil Ana , Herrada Eva , Ichii H. , Inverardi Luca , Kenyon Norma , Khan Aisha , Linetsky Elina , Montelongo J. , Peixoto Eduardo , Peterson K. , Ricordi Camillo , Szust J. , Wang X. , Xu Xiumin , Abdulla Muhamad H. , Ansite J. , Balamurugan A.N. , Bellin Melena D. , Brandenburg Mary , Gilmore T. , Harmon James V. , Hering Bernhard J. , Kandaswamy Raja , Loganathan Gopal , Mueller Kate , Papas Klearchos K. , Pedersen Jayne , Wilhelm Joshua J. , Witson Jean , Foss Aksel , Jenssen Trond , Dalton-Bakes Cornelia , Fu Hongxing , Kamoun Malek , Kearns Jane , Li Yanjing , Liu Chengyang , Luning-Prak Eline , Luo Yanping , Markmann Eileen , Min Zaw , Naji Ali , Palanjian Maral , Rickels Michael R. , Shlansky-Goldberg Richard , Vivek Kumar , Ziaie Amin Sam , Chebleck Peter , Danobeitia Juan Sebastian , Kaufman Luis Fernandez Dixon B. , Odorico Jon , Schneider Kristi , Zitur Laura , Brandhorst D. , Friiberg A. , Korsgren Olle , Nilsson Bo , Tufveson Gunnar , von Zur-MΈhlen Bengt , Feurer Irene 
Published: October 2022

OBJECTIVE
To determine long-term outcomes for islet-alone and islet-after-kidney transplantation in adults with type 1 diabetes complicated by impaired awareness of hypoglycemia.

RESEARCH DESIGN AND METHODS
This was a prospective interventional and observational cohort study of islet-alone (n = 48) and islet-after-kidney (n = 24) transplant recipients followed for up to 8 years after intraportal infusion of one or more purified human pancreatic islet products under standardized immunosuppression. Outcomes included duration of islet graft survival (stimulated C-peptide ≥0.3 ng/mL), on-target glycemic control (HbA1c &lt;7.0%), freedom from severe hypoglycemia, and insulin independence.

RESULTS
Of the 48 islet-alone and 24 islet-after-kidney transplantation recipients, 26 and 8 completed long-term follow-up with islet graft function, 15 and 7 withdrew from follow-up with islet graft function, and 7 and 9 experienced islet graft failure, respectively. Actuarial islet graft survival at median and final follow-up was 84% and 56% for islet-alone and 69% and 49% for islet-after-kidney (P = 0.007) with 77% and 49% of islet-alone and 57% and 35% of islet-after-kidney transplantation recipients maintaining posttransplant HbA1c &lt;7.0% (P = 0.0017); freedom from severe hypoglycemia was maintained at &gt;90% in both cohorts. Insulin independence was achieved by 74% of islet-alone and islet-after-kidney transplantation recipients, with more than one-half maintaining insulin independence during long-term follow-up. Kidney function remained stable during long-term follow-up in both cohorts, and rates of sensitization against HLA were low. Severe adverse events occurred at 0.31 per patient-year for islet-alone and 0.43 per patient-year for islet-after-kidney transplantation.

CONCLUSIONS
Islet transplantation results in durable islet graft survival permitting achievement of glycemic targets in the absence of severe hypoglycemia for most appropriately indicated recipients having impaired awareness of hypoglycemia, with acceptable safety of added immunosuppression for both islet-alone and islet-after-kidney transplantation.