Treatment resistant M-type phospholipase A2 receptor associated membranous nephropathy responds to obinutuzumab: a report of two cases.
Membranous nephropathy
Obinutuzumab
Resistant
Journal
BMC nephrology
ISSN: 1471-2369
Titre abrégé: BMC Nephrol
Pays: England
ID NLM: 100967793
Informations de publication
Date de publication:
07 04 2022
07 04 2022
Historique:
received:
17
01
2022
accepted:
28
03
2022
entrez:
8
4
2022
pubmed:
9
4
2022
medline:
12
4
2022
Statut:
epublish
Résumé
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. 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. Our cases add to the current limited literature on the successful use of obinutuzumab in PLA2R associated MN refractory to standard therapy including rituximab.
Sections du résumé
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.
Identifiants
pubmed: 35392837
doi: 10.1186/s12882-022-02761-3
pii: 10.1186/s12882-022-02761-3
pmc: PMC8991934
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Anticoagulants
0
Autoantibodies
0
Receptors, Phospholipase A2
0
Serum Albumin
0
Rituximab
4F4X42SYQ6
obinutuzumab
O43472U9X8
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
134Informations de copyright
© 2022. The Author(s).
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