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Updated: Feb 4, 2026
07:15
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
947
Prospective Cohort Study of Obinutuzumab in Rituximab-Resistant Primary Membranous Nephropathy
Matias Trillini1, Valentina Portalupi2, Alessia Gennarini2
1Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy.
Kidney International Reports
|February 2, 2026
Summary
Obinutuzumab effectively treats primary membranous nephropathy (MN) with persistent nephrotic syndrome (NS) resistant to rituximab. This therapy achieved high remission rates and improved patient outcomes safely.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- Primary membranous nephropathy (MN) with persistent nephrotic syndrome (NS) affects approximately 30% of patients who do not respond to rituximab therapy.
- Alternative treatment strategies are needed for patients with rituximab-resistant MN and NS.
Purpose of the Study:
- To evaluate the efficacy and safety of obinutuzumab in patients with primary MN and rituximab-resistant NS.
- To assess the impact of obinutuzumab on proteinuria, glomerular filtration rate (GFR), and B-cell depletion.
Main Methods:
- A prospective, single-arm, open-label trial involving 20 adults with MN and rituximab-resistant NS.
- Patients received three 1000 mg infusions of obinutuzumab.
- Outcomes including proteinuria, GFR, and B-cell levels were monitored for up to 24 months.
Main Results:
- At 12 months, 16 out of 20 patients achieved the composite endpoint of normo-albuminemia and NS remission (4 complete, 12 partial).
- Median 24-h proteinuria significantly decreased from 5.7 to 1.3 g/24 h, and serum albumin increased from 2.9 to 3.9 g/dl.
- Obinutuzumab treatment led to depletion of B cells and anti-phospholipase A2 receptor (PLA2R) antibodies, with significant improvements in dyslipidemia, hypocalcemia, and hypogammaglobulinemia.
Conclusions:
- Obinutuzumab is highly effective and safe for treating patients with primary MN and rituximab-resistant NS.
- The treatment can induce persistent remission and improve clinical parameters in this patient population.
- B-cell depletion and reduction in anti-PLA2R antibodies appear to be key mechanisms of action.
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