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Treatment resistant M-type phospholipase A2 receptor associated membranous nephropathy responds to obinutuzumab: a report of two cases

BACKGROUND: Membranous Nephropathy (MN) is a common cause of nephrotic syndrome (NS) in adults. Recognition of MN as an antibody mediated autoimmune disease has enabled the introduction of anti-B-cell therapy. Rituximab, a type I anti-CD20 antibody has been used in the management of MN, but has a 35...

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Autores principales: Hudson, Rebecca, Rawlings, Cassandra, Mon, Saw Yu, Jefferis, Julia, John, George T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8991934/
https://www.ncbi.nlm.nih.gov/pubmed/35392837
http://dx.doi.org/10.1186/s12882-022-02761-3
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author Hudson, Rebecca
Rawlings, Cassandra
Mon, Saw Yu
Jefferis, Julia
John, George T.
author_facet Hudson, Rebecca
Rawlings, Cassandra
Mon, Saw Yu
Jefferis, Julia
John, George T.
author_sort Hudson, Rebecca
collection PubMed
description BACKGROUND: Membranous Nephropathy (MN) is a common cause of nephrotic syndrome (NS) in adults. Recognition of MN as an antibody mediated autoimmune disease has enabled the introduction of anti-B-cell therapy. Rituximab, a type I anti-CD20 antibody has been used in the management of MN, but has a 35-45% failure rate. Obinutuzumab, a fully humanised type II anti-CD20 monoclonal antibody produces greater CD20 depletion and is superior to rituximab in the treatment of certain B-cell malignancies. In the two reports published to date involving nine patients with M-type phospholipase A2 receptor (PLA2R) associated MN (six of whom were rituximab resistant), treatment with obinutuzumab lead to immunological remission (IR) in 75% of patients, with improvement of proteinuria, normalisation of serum albumin and stable renal function in all patients. CASE PRESENTATION: We report on two cases of PLA2R-associated MN, two males aged 33 and 36-years, who presented with NS and bilateral sub massive pulmonary emboli requiring anticoagulation. Both were diagnosed serologically as PLA2R-associated MN where a renal biopsy was initially deferred due to bleeding risk on anticoagulation, but later confirmed. Both patients were refractory to multiple lines of therapy including rituximab, but achieved IR, normalistation of serum albumin, improved proteinuria and stable renal function with obinutuzumab. CONCLUSIONS: Our cases add to the current limited literature on the successful use of obinutuzumab in PLA2R associated MN refractory to standard therapy including rituximab. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12882-022-02761-3.
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spelling pubmed-89919342022-04-09 Treatment resistant M-type phospholipase A2 receptor associated membranous nephropathy responds to obinutuzumab: a report of two cases Hudson, Rebecca Rawlings, Cassandra Mon, Saw Yu Jefferis, Julia John, George T. BMC Nephrol Case Report BACKGROUND: Membranous Nephropathy (MN) is a common cause of nephrotic syndrome (NS) in adults. Recognition of MN as an antibody mediated autoimmune disease has enabled the introduction of anti-B-cell therapy. Rituximab, a type I anti-CD20 antibody has been used in the management of MN, but has a 35-45% failure rate. Obinutuzumab, a fully humanised type II anti-CD20 monoclonal antibody produces greater CD20 depletion and is superior to rituximab in the treatment of certain B-cell malignancies. In the two reports published to date involving nine patients with M-type phospholipase A2 receptor (PLA2R) associated MN (six of whom were rituximab resistant), treatment with obinutuzumab lead to immunological remission (IR) in 75% of patients, with improvement of proteinuria, normalisation of serum albumin and stable renal function in all patients. CASE PRESENTATION: We report on two cases of PLA2R-associated MN, two males aged 33 and 36-years, who presented with NS and bilateral sub massive pulmonary emboli requiring anticoagulation. Both were diagnosed serologically as PLA2R-associated MN where a renal biopsy was initially deferred due to bleeding risk on anticoagulation, but later confirmed. Both patients were refractory to multiple lines of therapy including rituximab, but achieved IR, normalistation of serum albumin, improved proteinuria and stable renal function with obinutuzumab. CONCLUSIONS: Our cases add to the current limited literature on the successful use of obinutuzumab in PLA2R associated MN refractory to standard therapy including rituximab. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12882-022-02761-3. BioMed Central 2022-04-07 /pmc/articles/PMC8991934/ /pubmed/35392837 http://dx.doi.org/10.1186/s12882-022-02761-3 Text en © The Author(s) 2022 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Case Report
Hudson, Rebecca
Rawlings, Cassandra
Mon, Saw Yu
Jefferis, Julia
John, George T.
Treatment resistant M-type phospholipase A2 receptor associated membranous nephropathy responds to obinutuzumab: a report of two cases
title Treatment resistant M-type phospholipase A2 receptor associated membranous nephropathy responds to obinutuzumab: a report of two cases
title_full Treatment resistant M-type phospholipase A2 receptor associated membranous nephropathy responds to obinutuzumab: a report of two cases
title_fullStr Treatment resistant M-type phospholipase A2 receptor associated membranous nephropathy responds to obinutuzumab: a report of two cases
title_full_unstemmed Treatment resistant M-type phospholipase A2 receptor associated membranous nephropathy responds to obinutuzumab: a report of two cases
title_short Treatment resistant M-type phospholipase A2 receptor associated membranous nephropathy responds to obinutuzumab: a report of two cases
title_sort treatment resistant m-type phospholipase a2 receptor associated membranous nephropathy responds to obinutuzumab: a report of two cases
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8991934/
https://www.ncbi.nlm.nih.gov/pubmed/35392837
http://dx.doi.org/10.1186/s12882-022-02761-3
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