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UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS), commonly caused by focal segmental glomerulosclerosis (FSGS), is associated with progression to stage 5 chronic kidney disease, requirement for kidney replacement therapy and a risk of disease recurrence post-kidney transplantation. Ofatumumab...

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Autores principales: Reynolds, Ben C., Lamb, Angela, Jones, Caroline A., Yadav, Pallavi, Tyerman, Kay S., Geddes, Colin C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674165/
https://www.ncbi.nlm.nih.gov/pubmed/34383125
http://dx.doi.org/10.1007/s00467-021-05248-9
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author Reynolds, Ben C.
Lamb, Angela
Jones, Caroline A.
Yadav, Pallavi
Tyerman, Kay S.
Geddes, Colin C.
author_facet Reynolds, Ben C.
Lamb, Angela
Jones, Caroline A.
Yadav, Pallavi
Tyerman, Kay S.
Geddes, Colin C.
author_sort Reynolds, Ben C.
collection PubMed
description BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS), commonly caused by focal segmental glomerulosclerosis (FSGS), is associated with progression to stage 5 chronic kidney disease, requirement for kidney replacement therapy and a risk of disease recurrence post-kidney transplantation. Ofatumumab (OFA) is a fully humanised monoclonal antibody to CD20, with similar mechanisms of action to rituximab (RTX). METHODS: We report a case series of seven UK patients (five paediatric, two adult), all of whom developed FSGS recurrence after kidney transplantation and received OFA as part of their therapeutic intervention. All also received concomitant plasmapheresis. The 2-year outcome of these seven patients is reported, describing clinical course, kidney function and proteinuria. RESULTS: Four patients (all paediatric) achieved complete urinary remission with minimal proteinuria 12 months post-treatment. Three of those four also had normal graft function. Two patients showed partial remission—brief improvement to non-nephrotic proteinuria (197 mg/mmol) in one patient, maintained improvement in kidney function (estimated glomerular filtration rate 76 ml/min/1.73 m(2)) in the other. One patient did not demonstrate any response. CONCLUSIONS: OFA may represent a useful addition to therapeutic options in the management of FSGS recurrence post-transplantation, including where RTX has shown no benefit. Concomitant plasmapheresis in all patients prevents any definitive conclusion that OFA was the beneficial intervention. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00467-021-05248-9.
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spelling pubmed-86741652021-12-28 UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant Reynolds, Ben C. Lamb, Angela Jones, Caroline A. Yadav, Pallavi Tyerman, Kay S. Geddes, Colin C. Pediatr Nephrol Original Article BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS), commonly caused by focal segmental glomerulosclerosis (FSGS), is associated with progression to stage 5 chronic kidney disease, requirement for kidney replacement therapy and a risk of disease recurrence post-kidney transplantation. Ofatumumab (OFA) is a fully humanised monoclonal antibody to CD20, with similar mechanisms of action to rituximab (RTX). METHODS: We report a case series of seven UK patients (five paediatric, two adult), all of whom developed FSGS recurrence after kidney transplantation and received OFA as part of their therapeutic intervention. All also received concomitant plasmapheresis. The 2-year outcome of these seven patients is reported, describing clinical course, kidney function and proteinuria. RESULTS: Four patients (all paediatric) achieved complete urinary remission with minimal proteinuria 12 months post-treatment. Three of those four also had normal graft function. Two patients showed partial remission—brief improvement to non-nephrotic proteinuria (197 mg/mmol) in one patient, maintained improvement in kidney function (estimated glomerular filtration rate 76 ml/min/1.73 m(2)) in the other. One patient did not demonstrate any response. CONCLUSIONS: OFA may represent a useful addition to therapeutic options in the management of FSGS recurrence post-transplantation, including where RTX has shown no benefit. Concomitant plasmapheresis in all patients prevents any definitive conclusion that OFA was the beneficial intervention. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00467-021-05248-9. Springer Berlin Heidelberg 2021-08-12 2022 /pmc/articles/PMC8674165/ /pubmed/34383125 http://dx.doi.org/10.1007/s00467-021-05248-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Reynolds, Ben C.
Lamb, Angela
Jones, Caroline A.
Yadav, Pallavi
Tyerman, Kay S.
Geddes, Colin C.
UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant
title UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant
title_full UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant
title_fullStr UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant
title_full_unstemmed UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant
title_short UK experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant
title_sort uk experience of ofatumumab in recurrence of focal segmental glomerulosclerosis post-kidney transplant
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8674165/
https://www.ncbi.nlm.nih.gov/pubmed/34383125
http://dx.doi.org/10.1007/s00467-021-05248-9
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