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A Multi-Modal Approach to Islet and Pancreas Transplantation With Calcineurin-Sparing Immunosuppression Maintains Long-Term Insulin Independence in Patients With Type I Diabetes

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 consecutiv...

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Autores principales: Wisel, Steven A., Posselt, Andrew M., Szot, Gregory L., Nunez, Miguel, Santos-Parker, Keli, Gardner, James M., Worner, Giulia, Roll, Garrett R., Syed, Shareef, Kelly, Yvonne, Ward, Casey, Tavakol, Medhi, Johnson, Kristina, Masharani, Umesh, Stock, Peter G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10285771/
https://www.ncbi.nlm.nih.gov/pubmed/37359825
http://dx.doi.org/10.3389/ti.2023.11367
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author Wisel, Steven A.
Posselt, Andrew M.
Szot, Gregory L.
Nunez, Miguel
Santos-Parker, Keli
Gardner, James M.
Worner, Giulia
Roll, Garrett R.
Syed, Shareef
Kelly, Yvonne
Ward, Casey
Tavakol, Medhi
Johnson, Kristina
Masharani, Umesh
Stock, Peter G.
author_facet Wisel, Steven A.
Posselt, Andrew M.
Szot, Gregory L.
Nunez, Miguel
Santos-Parker, Keli
Gardner, James M.
Worner, Giulia
Roll, Garrett R.
Syed, Shareef
Kelly, Yvonne
Ward, Casey
Tavakol, Medhi
Johnson, Kristina
Masharani, Umesh
Stock, Peter G.
author_sort Wisel, Steven A.
collection PubMed
description 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.
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spelling pubmed-102857712023-06-23 A Multi-Modal Approach to Islet and Pancreas Transplantation With Calcineurin-Sparing Immunosuppression Maintains Long-Term Insulin Independence in Patients With Type I Diabetes Wisel, Steven A. Posselt, Andrew M. Szot, Gregory L. Nunez, Miguel Santos-Parker, Keli Gardner, James M. Worner, Giulia Roll, Garrett R. Syed, Shareef Kelly, Yvonne Ward, Casey Tavakol, Medhi Johnson, Kristina Masharani, Umesh Stock, Peter G. Transpl Int Health Archive 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. Frontiers Media S.A. 2023-06-08 /pmc/articles/PMC10285771/ /pubmed/37359825 http://dx.doi.org/10.3389/ti.2023.11367 Text en Copyright © 2023 Wisel, Posselt, Szot, Nunez, Santos-Parker, Gardner, Worner, Roll, Syed, Kelly, Ward, Tavakol, Johnson, Masharani and Stock. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Health Archive
Wisel, Steven A.
Posselt, Andrew M.
Szot, Gregory L.
Nunez, Miguel
Santos-Parker, Keli
Gardner, James M.
Worner, Giulia
Roll, Garrett R.
Syed, Shareef
Kelly, Yvonne
Ward, Casey
Tavakol, Medhi
Johnson, Kristina
Masharani, Umesh
Stock, Peter G.
A Multi-Modal Approach to Islet and Pancreas Transplantation With Calcineurin-Sparing Immunosuppression Maintains Long-Term Insulin Independence in Patients With Type I Diabetes
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
title_full A Multi-Modal Approach to Islet and Pancreas Transplantation With Calcineurin-Sparing Immunosuppression Maintains Long-Term Insulin Independence in Patients With Type I Diabetes
title_fullStr A Multi-Modal Approach to Islet and Pancreas Transplantation With Calcineurin-Sparing Immunosuppression Maintains Long-Term Insulin Independence in Patients With Type I Diabetes
title_full_unstemmed A Multi-Modal Approach to Islet and Pancreas Transplantation With Calcineurin-Sparing Immunosuppression Maintains Long-Term Insulin Independence in Patients With Type I Diabetes
title_short A Multi-Modal Approach to Islet and Pancreas Transplantation With Calcineurin-Sparing Immunosuppression Maintains Long-Term Insulin Independence in Patients With Type I Diabetes
title_sort multi-modal approach to islet and pancreas transplantation with calcineurin-sparing immunosuppression maintains long-term insulin independence in patients with type i diabetes
topic Health Archive
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10285771/
https://www.ncbi.nlm.nih.gov/pubmed/37359825
http://dx.doi.org/10.3389/ti.2023.11367
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