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Review
. 2025 Feb 21:14:2024-9-1.
doi: 10.7573/dic.2024-9-1. eCollection 2025.

Obinutuzumab in membranous nephropathy: a potential game-changer in treatment

Concetto Sessa  1 , Dario Galeano  1 , Luca Zanoli  2 , Marco Delsante  3 , Giovanni Maria Rossi  3 , Walter Morale  1
Affiliations
Review

Obinutuzumab in membranous nephropathy: a potential game-changer in treatment

Concetto Sessa et al. Drugs Context. .

Abstract

Membranous nephropathy (MN) is a kidney disease characterized by thickening of the glomerular basement membrane due to immune complex deposition, often leading to nephrotic syndrome and potentially progressing to end-stage renal disease. Traditional treatments, including corticosteroids and immunosuppressive agents, have significant side-effects and variable efficacy. Recently, obinutuzumab, a fully humanized monoclonal antibody targeting CD20, has emerged as a promising therapeutic option for MN. Herein, we review the pathophysiology of MN, the mechanism of action of obinutuzumab, clinical data supporting its use and highlight its potential as a game changer in MN treatment.

Keywords: B cell depletion; autoimmune kidney disease; immunotherapy; membranous nephropathy; obinutuzumab; proteinuria.

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Conflict of interest statement

Disclosure and potential conflicts of interest: The authors declare that they have no conflicts of interest relevant to this manuscript. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors is available for download at: https://www.drugsincontext.com/wp-content/uploads/2025/01/dic.2024-9-1-COI.pdf

Figures

Figure 1
Figure 1
PRISMA flow diagram.
Figure 2
Figure 2
Mechanism of action of Obinutuzumab. Obinutuzumab recognizes CD20 and has a modified elbow-hinge amino acid sequence (substitution of leucine by valine) compared to type 1 agents, resulting in spatial alterations to the CD20-mAb assembly complex on B cells (Panel a). De-fucosylation of the Fc region enhances its binding affinity to the FcγRIII receptor, leading to increased direct cell death induction and enhanced antibody-dependent phagocytosis (b) and antibody-dependent cellular cytotoxicity (c). Moreover, after binding CD20, obinutuzumab can activate complement-dependent cytotoxicity (d) and provide direct cellular apoptosis (e).
See this image and copyright information in PMC

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