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Belatacept in kidney transplant patients with systemic lupus erythematosus

OBJECTIVES: Lupus nephritis (LN) requires renal replacement therapy in 10%–30% of patients. About 30% of these patients receive a kidney transplant. Belatacept is a second-generation, selective, T-cell co-stimulator blocker (inhibits cytotoxic, T-lymphocyte antigen 4, CTLA-4) used as an alternative...

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Autores principales: Carrión-Barberà, Irene, Fajardo, Melissa, Danias, George, Tsapepas, Demetra, Gartshteyn, Yevgeniya, Fernandez, Hilda, Askanase, Anca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928461/
https://www.ncbi.nlm.nih.gov/pubmed/31908816
http://dx.doi.org/10.1136/lupus-2019-000355
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author Carrión-Barberà, Irene
Fajardo, Melissa
Danias, George
Tsapepas, Demetra
Gartshteyn, Yevgeniya
Fernandez, Hilda
Askanase, Anca
author_facet Carrión-Barberà, Irene
Fajardo, Melissa
Danias, George
Tsapepas, Demetra
Gartshteyn, Yevgeniya
Fernandez, Hilda
Askanase, Anca
author_sort Carrión-Barberà, Irene
collection PubMed
description OBJECTIVES: Lupus nephritis (LN) requires renal replacement therapy in 10%–30% of patients. About 30% of these patients receive a kidney transplant. Belatacept is a second-generation, selective, T-cell co-stimulator blocker (inhibits cytotoxic, T-lymphocyte antigen 4, CTLA-4) used as an alternative to calcineurin inhibitors (CNI) for maintenance regimens after kidney transplantation. The pathogenic relevance of CTLA-4 inhibition and the favourable cardiovascular profile of belatacept make it an attractive therapeutic option in systemic lupus erythematosus (SLE). Intravenous administration of belatacept ensures therapeutic adherence. METHODS: This retrospective, single-centre study evaluates the outcomes of LN kidney transplant recipients treated with belatacept for reasons not related to SLE at the Columbia University Lupus and Renal Transplant Cohort. RESULTS: Belatacept was started in six patients on CNI regimens at 15.5±17.1 months following transplantation for LN. In five patients, creatinine levels stabilised 6 months after belatacept, one returned to haemodialysis due to CNI toxicity and pyelonephritis and one relisted for a kidney transplant following acute cellular rejection and cortical necrosis. Five patients are followed for extrarenal lupus; no extrarenal manifestations were documented in the other two patients. Data on SLE disease activity pre-belatacept and post-belatacept were available and scored in three patients using the SLE Disease Activity Index Glucocorticosteroid Index (SLEDAI-2KG), which accounts for clinical and laboratory manifestations, as well as steroid dose. Mean SLEDAI-2KG decreased from 13 to 7.6. CONCLUSION: Belatacept in LN kidney transplant recipients may decrease extrarenal manifestations, attenuate CNI toxicity and stabilise allograft function, providing a better alternative to CNI regimens. Furthermore, these data suggest that belatacept, although initiated for reasons not related to SLE, might have a beneficial effect in SLE.
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spelling pubmed-69284612020-01-06 Belatacept in kidney transplant patients with systemic lupus erythematosus Carrión-Barberà, Irene Fajardo, Melissa Danias, George Tsapepas, Demetra Gartshteyn, Yevgeniya Fernandez, Hilda Askanase, Anca Lupus Sci Med Immunology and Inflammation OBJECTIVES: Lupus nephritis (LN) requires renal replacement therapy in 10%–30% of patients. About 30% of these patients receive a kidney transplant. Belatacept is a second-generation, selective, T-cell co-stimulator blocker (inhibits cytotoxic, T-lymphocyte antigen 4, CTLA-4) used as an alternative to calcineurin inhibitors (CNI) for maintenance regimens after kidney transplantation. The pathogenic relevance of CTLA-4 inhibition and the favourable cardiovascular profile of belatacept make it an attractive therapeutic option in systemic lupus erythematosus (SLE). Intravenous administration of belatacept ensures therapeutic adherence. METHODS: This retrospective, single-centre study evaluates the outcomes of LN kidney transplant recipients treated with belatacept for reasons not related to SLE at the Columbia University Lupus and Renal Transplant Cohort. RESULTS: Belatacept was started in six patients on CNI regimens at 15.5±17.1 months following transplantation for LN. In five patients, creatinine levels stabilised 6 months after belatacept, one returned to haemodialysis due to CNI toxicity and pyelonephritis and one relisted for a kidney transplant following acute cellular rejection and cortical necrosis. Five patients are followed for extrarenal lupus; no extrarenal manifestations were documented in the other two patients. Data on SLE disease activity pre-belatacept and post-belatacept were available and scored in three patients using the SLE Disease Activity Index Glucocorticosteroid Index (SLEDAI-2KG), which accounts for clinical and laboratory manifestations, as well as steroid dose. Mean SLEDAI-2KG decreased from 13 to 7.6. CONCLUSION: Belatacept in LN kidney transplant recipients may decrease extrarenal manifestations, attenuate CNI toxicity and stabilise allograft function, providing a better alternative to CNI regimens. Furthermore, these data suggest that belatacept, although initiated for reasons not related to SLE, might have a beneficial effect in SLE. BMJ Publishing Group 2019-12-22 /pmc/articles/PMC6928461/ /pubmed/31908816 http://dx.doi.org/10.1136/lupus-2019-000355 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Immunology and Inflammation
Carrión-Barberà, Irene
Fajardo, Melissa
Danias, George
Tsapepas, Demetra
Gartshteyn, Yevgeniya
Fernandez, Hilda
Askanase, Anca
Belatacept in kidney transplant patients with systemic lupus erythematosus
title Belatacept in kidney transplant patients with systemic lupus erythematosus
title_full Belatacept in kidney transplant patients with systemic lupus erythematosus
title_fullStr Belatacept in kidney transplant patients with systemic lupus erythematosus
title_full_unstemmed Belatacept in kidney transplant patients with systemic lupus erythematosus
title_short Belatacept in kidney transplant patients with systemic lupus erythematosus
title_sort belatacept in kidney transplant patients with systemic lupus erythematosus
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928461/
https://www.ncbi.nlm.nih.gov/pubmed/31908816
http://dx.doi.org/10.1136/lupus-2019-000355
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