RARE DISEASE
Primary membranous glomerulonephritis
Primary membranous glomerulonephritis
Primary membranous glomerulonephritis
Synonyms: Idiopathic membranous glomerulonephritis, Primary membranous nephropathy
Synonyms: Idiopathic membranous glomerulonephritis, Primary membranous nephropathy
Synonyms: Idiopathic membranous glomerulonephritis, Primary membranous nephropathy
Drug discovery
12
drugs
With orphan designations
Overview
Primary Membranous Glomerulonephritis (PMN) is an autoimmune kidney disease characterized by immune complex deposition in glomeruli, primarily targeting podocyte antigens (e.g., PLA2R in 70%, THSD7A in 3-9%). It manifests as nephrotic syndrome or proteinuria, with 30-40% progressing to end-stage kidney disease (ESKD) within 10 years. Diagnosis combines serum anti-PLA2R/THSD7A antibodies and kidney biopsy with immunohistochemistry [1][2][6][10].
Therapies
Categories: rare renal diseases, rare transplant-related disorders
Research Papers
1,382 drug discovery papers about Primary membranous glomerulonephritis, with 4 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,382 drug discovery papers about Primary membranous glomerulonephritis, with 4 first-in-class and 6 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-08-05 | Efficacy and safety of obinutuzumab in refractory membranous nephropathy: a single-arm meta-analysis.
Membranous nephropathy (MN) constitutes an autoimmune glomerular disorder and represents the most frequent etiology of primary nephrotic syndrome in adults. Although obinutuzumab exhibits favorable efficacy in managing refractory MN, outcomes diverge across individual investigations. Consequently, the present meta-analysis is undertaken to systematically evaluate the clinical efficacy and safety of obinutuzumab in individuals with refractory MN. A systematic search was conducted across the Cochrane Library, Embase, Web of Science, and PubMed to determine relevant clinical investigations published up to November 12, 2025. Treatment effects were quantified employing the pooled proportion rate with 95% confidence interval (CI), mean difference (MD, 95% CI), and standardized mean difference (SMD, 95% CI). Heterogeneity was examined via the I² statistic. Subgroup analyses were implemented based on the geographic distribution of the study population and duration of follow-up. All extracted data were subjected to statistical analysis using R (v4.5.2). The present meta-analysis ultimately incorporated 12 articles (222 individuals) after applying the eligibility criteria. Concerning remission rates, the overall clinical remission rate reached 86% (95% CI: 80% to 90%), the complete clinical remission rate stood at 31% (25% to 37%), the partial clinical remission rate was 55% (49% to 63%), and the immunologic remission rate achieved 88% (81% to 92%). Obinutuzumab reduced proteinuria (SMD = -1.2, 95%CI -1.37 to -1.03) and raised serum albumin (MD = 12.5, 95%CI 9.91-15.08), while eGFR showed no significant change (MD = 3.23, 95%CI -3.76-10.21). The pooled adverse event rate was 29% (95%CI 15%-48%), with two fatal pneumonia-related events: severe COVID-19 pneumonia and pneumonia-induced respiratory failure. Obinutuzumab demonstrates marked efficacy in treating refractory MN, with an overall clinical remission rate of 86% and a low incidence of severe adverse events. This profile signifies a potential therapeutic role for this condition. However, all raw data included in this meta-analysis were derived from uncontrolled retrospective single-arm trials and case series. Given factors such as selection bias, the remission rate may be overestimated. Large-scale, multicenter randomized controlled trials are necessary for verification in future investigations. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251231344.
2026-08-05 | Programmed Cell Death: A Key Mechanism of Traditional Chinese Medicine in the Treatment of Membranous Nephropathy.
Membranous nephropathy (MN) is the leading cause of adult nephrotic syndrome with rising global incidence. A substantial proportion of patients progress to end-stage renal disease. Multiple programmed cell death (PCD) pathways-including apoptosis, pyroptosis, ferroptosis, and autophagy-are activated by complement-dependent and -independent pathogenic factors, collectively driving podocyte injury and MN progression. Current immunosuppressive therapies are limited by adverse reactions and variable responses. Traditional Chinese medicine (TCM), characterized by multi-component, multi-target, and multi-pathway regulation, shows therapeutic advantages in MN. To systematically review the regulatory mechanisms of PCD in MN, summarize the molecular basis of TCM interventions targeting PCD, and identify current research limitations and future directions. This narrative review systematically elaborates the regulatory association between PCD and podocyte injury in MN. Literatures were systematically retrieved from PubMed, Embase and China National Knowledge Infrastructure (CNKI) from the establishment of each database to May 2026, and 41 preclinical studies exploring TCM modulation of PCD in MN were included after strict screening. Complement-dependent and complement-independent pathways in MN can synergistically initiate podocyte apoptosis, pyroptosis, ferroptosis, and autophagy dysfunction. TCM can regulate PCD through core signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1), mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase/forkhead box O1 (JNK/FoxO1), and PTEN-induced kinase 1/Parkin (PINK1/Parkin), while simultaneously intervening in non-PCD pathological processes including inflammation, oxidative stress, and renal fibrosis. Clinical evidence further indicates that TCM or combined with conventional therapy can elevate MN remission rates and decrease adverse reactions. PCD represents a core mechanism mediating podocyte injury and MN progression. TCM effectively modulates PCD imbalance through multi-target regulation, demonstrating prominent clinical efficacy and safety. These findings provide a theoretical basis and translational direction for developing high-efficacy, low-toxicity therapeutic strategies for MN.
2026-07-31 | Proteinuria selectivity index as a predictor of remission and rituximab efficacy in primary membranous nephropathy: a single-center retrospective analysis
The protein selectivity index (PSI) has been proposed as a prognostic marker in nephrotic syndrome, but its prognostic value in primary membranous nephropathy (PMN) has not been well established in the modern era of advanced diagnostics and therapeutics. This study assessed the predictive value of PSI for proteinuria remission and response to rituximab therapy. A total of 73 patients with PMN treated between September 2021 and September 2024 were included in this single-center retrospective study, all with at least six months of follow-up. PSI was calculated from serum and urinary immunoglobulin G and transferrin. The optimal PSI cutoff for predicting complete remission was 0.303. Low-PSI (<0.303) patients had higher complete remission rates than high-PSI (≥0.303) patients (59.65% vs. 12.50%, p = 0.001). No significant differences were observed in eGFR changes or CKD progression. Kaplan-Meier analysis demonstrated a significantly higher cumulative incidence of complete remission in the low-PSI group (p = 0.016). Cox regression confirmed that patients with low PSI were more likely to achieve complete remission (HR = 4.88, 95% CI: 1.17–20.36, p = 0.030). In the rituximab subgroup, a cutoff of 0.313 identified better responders (51.35% vs. 0%, p = 0.003). The albumin-based alternative index correlated strongly with traditional PSI (r = 0.839, p < 0.001). In conclusion, PSI predicts proteinuria remission and treatment response in PMN. Prospective multicenter studies are needed to validate its clinical utility. Primary membranous nephropathy (PMN) is an autoimmune kidney disease characterized by high levels of protein in the urine. Treatment responses vary widely, and simple tools to predict outcomes remain limited. In this study, we evaluated the protein selectivity index (PSI), which reflects the relative clearance of large proteins compared with smaller proteins in the urine. We found that patients with lower PSI values were more likely to achieve complete remission and responded better to rituximab, while higher PSI was associated with poorer outcomes and more severe kidney damage. A simpler index based on routinely measured proteins (albumin and IgG) showed similar performance, suggesting better clinical practicality. Overall, PSI may help identify patients more likely to benefit from treatment and support personalized care, although larger studies are needed for validation. What is known: Primary membranous nephropathy (PMN) shows highly variable treatment responses, and although the protein selectivity index (PSI) reflects glomerular permeability injury, its clinical utility in predicting outcomes remains uncertain in the modern treatment era. This Study add: This study demonstrates that lower PSI is associated with a higher likelihood of complete proteinuria remission and better response to rituximab in PMN. It also identifies a simplified albumin-based index with comparable performance, supporting its feasibility in routine clinical practice. Potential Impact: PSI may serve as a practical adjunctive tool for risk stratification, with potential to identify patients most likely to benefit from rituximab therapy.
2026-07-25 | Neuro-renal syndrome (NRS) in autoimmune nodopathies and paranodopathies: A warning to consider the diagnosis when anti-node and paranode antibody tests are difficult to perform.
Neuro - renal syndrome (NRS), a neuroimmunomediated entity that presents with acute nephrotic syndrome (primarily membranous glomerulonephritis), recurrent proteinuria, and even acute renal failure requiring dialysis, has been reported with varying prevalence in patients with immunomediated neuropathies and paraneoplastic syndromes. Pathophysiologically, IgG 3 and IgG 4 antibodies target the peripheral nervous system (PNS) and central nervous system (CNS), leading to predominantly distal weakness, sensory ataxia, and electrophysiological abnormalities. The patient tends to be refractory to intravenous immunoglobulin due to the pathophysiology of IgG 3 or IgG 4 antibodies but responds favorably to plasmapheresis and anti- CD 20 therapy. Additional investigations revealed a definitive diagnosis through positive antibody levels on tests such as the transfected CBA, using commercial or in- house kits. To describe the relationship between the clinical presentation of nodopathies and paranodopathies with immunomediated origins and acute nephrotic syndrome, recurrent proteinuria, and acute renal failure requiring dialysis, and to identify factors that alter prognosis and therapeutic options. Systematic review of NRS. Our postdoctoral project was approved by the local ethics committee (protocol no. 34144620.7.1001.5363.7.1001.5363. 7. 1001. 5363. 7. 1001. 5363) at FMUSP- RP. NRS has been recently described and partially explained, with neuropathies linked to nodal antigens such as neurofascin (NF) 146 and 188, NF paranodal 155, contactin 1 (CNTN- 1), and the contactin 1 (CASPR- 1) complex, representing warning signs consistent with an expanded phenotype and therapeutic refractoriness. We believe that NRS (and its variants) is a comorbidity that contributes to the pathophysiology of immunomediated conditions, with potentially catastrophic evolution if not recognized early. To describe NRS (with its variants) with early renal involvement and failure of first- line immunotherapies, due to the predominance of IgG 3 or IgG 4 antibodies. Identifying the clinical spectrum of NRS in nodopathies and paranodopathies can directly impact management, including early plasmapheresis and anti- CD 20 therapies, aiming to prevent early axonal loss, irreversible comorbidities, and increased mortality in a subacute- onset chronic neuropathy.
2026-07-25 | Serum PLA2R-negative, biopsy-proven PLA2R-positive primary membranous nephropathy in a dichorionic-diamniotic twin pregnancy.
Primary membranous nephropathy (PMN) in pregnancy is rare and poses significant risks including pre-eclampsia, preterm delivery, low birth weight and fetal death. Anti-phospholipase A2 receptor (PLA2R) antibodies are used to confirm diagnosis.We report a case of biopsy-confirmed PLA2R-positive but seronegative PMN in a woman in her late 20s with a dichorionic-diamniotic twin pregnancy. Initial hypoalbuminaemia was attributed to intercurrent infection but was later recognised as nephrotic syndrome at 20+6 weeks gestation. Renal biopsy at 21 weeks confirmed PMN with positive PLA2R and IgG4 staining, despite negative serum PLA2R antibodies.She was managed with tacrolimus and rituximab, with close monitoring and delivered viable twins via emergency caesarean at 33+3 weeks following premature rupture of membranes. Both maternal disease and neonatal outcomes were favourable. This case highlights the challenges in diagnosing and managing seronegative PMN during pregnancy and supports the role of renal biopsy and rituximab in selected patients.
2026-08-05 | Efficacy and safety of obinutuzumab in refractory membranous nephropathy: a single-arm meta-analysis.
Membranous nephropathy (MN) constitutes an autoimmune glomerular disorder and represents the most frequent etiology of primary nephrotic syndrome in adults. Although obinutuzumab exhibits favorable efficacy in managing refractory MN, outcomes diverge across individual investigations. Consequently, the present meta-analysis is undertaken to systematically evaluate the clinical efficacy and safety of obinutuzumab in individuals with refractory MN. A systematic search was conducted across the Cochrane Library, Embase, Web of Science, and PubMed to determine relevant clinical investigations published up to November 12, 2025. Treatment effects were quantified employing the pooled proportion rate with 95% confidence interval (CI), mean difference (MD, 95% CI), and standardized mean difference (SMD, 95% CI). Heterogeneity was examined via the I² statistic. Subgroup analyses were implemented based on the geographic distribution of the study population and duration of follow-up. All extracted data were subjected to statistical analysis using R (v4.5.2). The present meta-analysis ultimately incorporated 12 articles (222 individuals) after applying the eligibility criteria. Concerning remission rates, the overall clinical remission rate reached 86% (95% CI: 80% to 90%), the complete clinical remission rate stood at 31% (25% to 37%), the partial clinical remission rate was 55% (49% to 63%), and the immunologic remission rate achieved 88% (81% to 92%). Obinutuzumab reduced proteinuria (SMD = -1.2, 95%CI -1.37 to -1.03) and raised serum albumin (MD = 12.5, 95%CI 9.91-15.08), while eGFR showed no significant change (MD = 3.23, 95%CI -3.76-10.21). The pooled adverse event rate was 29% (95%CI 15%-48%), with two fatal pneumonia-related events: severe COVID-19 pneumonia and pneumonia-induced respiratory failure. Obinutuzumab demonstrates marked efficacy in treating refractory MN, with an overall clinical remission rate of 86% and a low incidence of severe adverse events. This profile signifies a potential therapeutic role for this condition. However, all raw data included in this meta-analysis were derived from uncontrolled retrospective single-arm trials and case series. Given factors such as selection bias, the remission rate may be overestimated. Large-scale, multicenter randomized controlled trials are necessary for verification in future investigations. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD420251231344.
2026-08-05 | Programmed Cell Death: A Key Mechanism of Traditional Chinese Medicine in the Treatment of Membranous Nephropathy.
Membranous nephropathy (MN) is the leading cause of adult nephrotic syndrome with rising global incidence. A substantial proportion of patients progress to end-stage renal disease. Multiple programmed cell death (PCD) pathways-including apoptosis, pyroptosis, ferroptosis, and autophagy-are activated by complement-dependent and -independent pathogenic factors, collectively driving podocyte injury and MN progression. Current immunosuppressive therapies are limited by adverse reactions and variable responses. Traditional Chinese medicine (TCM), characterized by multi-component, multi-target, and multi-pathway regulation, shows therapeutic advantages in MN. To systematically review the regulatory mechanisms of PCD in MN, summarize the molecular basis of TCM interventions targeting PCD, and identify current research limitations and future directions. This narrative review systematically elaborates the regulatory association between PCD and podocyte injury in MN. Literatures were systematically retrieved from PubMed, Embase and China National Knowledge Infrastructure (CNKI) from the establishment of each database to May 2026, and 41 preclinical studies exploring TCM modulation of PCD in MN were included after strict screening. Complement-dependent and complement-independent pathways in MN can synergistically initiate podocyte apoptosis, pyroptosis, ferroptosis, and autophagy dysfunction. TCM can regulate PCD through core signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1), mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase/forkhead box O1 (JNK/FoxO1), and PTEN-induced kinase 1/Parkin (PINK1/Parkin), while simultaneously intervening in non-PCD pathological processes including inflammation, oxidative stress, and renal fibrosis. Clinical evidence further indicates that TCM or combined with conventional therapy can elevate MN remission rates and decrease adverse reactions. PCD represents a core mechanism mediating podocyte injury and MN progression. TCM effectively modulates PCD imbalance through multi-target regulation, demonstrating prominent clinical efficacy and safety. These findings provide a theoretical basis and translational direction for developing high-efficacy, low-toxicity therapeutic strategies for MN.
2026-07-31 | Proteinuria selectivity index as a predictor of remission and rituximab efficacy in primary membranous nephropathy: a single-center retrospective analysis
The protein selectivity index (PSI) has been proposed as a prognostic marker in nephrotic syndrome, but its prognostic value in primary membranous nephropathy (PMN) has not been well established in the modern era of advanced diagnostics and therapeutics. This study assessed the predictive value of PSI for proteinuria remission and response to rituximab therapy. A total of 73 patients with PMN treated between September 2021 and September 2024 were included in this single-center retrospective study, all with at least six months of follow-up. PSI was calculated from serum and urinary immunoglobulin G and transferrin. The optimal PSI cutoff for predicting complete remission was 0.303. Low-PSI (<0.303) patients had higher complete remission rates than high-PSI (≥0.303) patients (59.65% vs. 12.50%, p = 0.001). No significant differences were observed in eGFR changes or CKD progression. Kaplan-Meier analysis demonstrated a significantly higher cumulative incidence of complete remission in the low-PSI group (p = 0.016). Cox regression confirmed that patients with low PSI were more likely to achieve complete remission (HR = 4.88, 95% CI: 1.17–20.36, p = 0.030). In the rituximab subgroup, a cutoff of 0.313 identified better responders (51.35% vs. 0%, p = 0.003). The albumin-based alternative index correlated strongly with traditional PSI (r = 0.839, p < 0.001). In conclusion, PSI predicts proteinuria remission and treatment response in PMN. Prospective multicenter studies are needed to validate its clinical utility. Primary membranous nephropathy (PMN) is an autoimmune kidney disease characterized by high levels of protein in the urine. Treatment responses vary widely, and simple tools to predict outcomes remain limited. In this study, we evaluated the protein selectivity index (PSI), which reflects the relative clearance of large proteins compared with smaller proteins in the urine. We found that patients with lower PSI values were more likely to achieve complete remission and responded better to rituximab, while higher PSI was associated with poorer outcomes and more severe kidney damage. A simpler index based on routinely measured proteins (albumin and IgG) showed similar performance, suggesting better clinical practicality. Overall, PSI may help identify patients more likely to benefit from treatment and support personalized care, although larger studies are needed for validation. What is known: Primary membranous nephropathy (PMN) shows highly variable treatment responses, and although the protein selectivity index (PSI) reflects glomerular permeability injury, its clinical utility in predicting outcomes remains uncertain in the modern treatment era. This Study add: This study demonstrates that lower PSI is associated with a higher likelihood of complete proteinuria remission and better response to rituximab in PMN. It also identifies a simplified albumin-based index with comparable performance, supporting its feasibility in routine clinical practice. Potential Impact: PSI may serve as a practical adjunctive tool for risk stratification, with potential to identify patients most likely to benefit from rituximab therapy.
2026-07-25 | Neuro-renal syndrome (NRS) in autoimmune nodopathies and paranodopathies: A warning to consider the diagnosis when anti-node and paranode antibody tests are difficult to perform.
Neuro - renal syndrome (NRS), a neuroimmunomediated entity that presents with acute nephrotic syndrome (primarily membranous glomerulonephritis), recurrent proteinuria, and even acute renal failure requiring dialysis, has been reported with varying prevalence in patients with immunomediated neuropathies and paraneoplastic syndromes. Pathophysiologically, IgG 3 and IgG 4 antibodies target the peripheral nervous system (PNS) and central nervous system (CNS), leading to predominantly distal weakness, sensory ataxia, and electrophysiological abnormalities. The patient tends to be refractory to intravenous immunoglobulin due to the pathophysiology of IgG 3 or IgG 4 antibodies but responds favorably to plasmapheresis and anti- CD 20 therapy. Additional investigations revealed a definitive diagnosis through positive antibody levels on tests such as the transfected CBA, using commercial or in- house kits. To describe the relationship between the clinical presentation of nodopathies and paranodopathies with immunomediated origins and acute nephrotic syndrome, recurrent proteinuria, and acute renal failure requiring dialysis, and to identify factors that alter prognosis and therapeutic options. Systematic review of NRS. Our postdoctoral project was approved by the local ethics committee (protocol no. 34144620.7.1001.5363.7.1001.5363. 7. 1001. 5363. 7. 1001. 5363) at FMUSP- RP. NRS has been recently described and partially explained, with neuropathies linked to nodal antigens such as neurofascin (NF) 146 and 188, NF paranodal 155, contactin 1 (CNTN- 1), and the contactin 1 (CASPR- 1) complex, representing warning signs consistent with an expanded phenotype and therapeutic refractoriness. We believe that NRS (and its variants) is a comorbidity that contributes to the pathophysiology of immunomediated conditions, with potentially catastrophic evolution if not recognized early. To describe NRS (with its variants) with early renal involvement and failure of first- line immunotherapies, due to the predominance of IgG 3 or IgG 4 antibodies. Identifying the clinical spectrum of NRS in nodopathies and paranodopathies can directly impact management, including early plasmapheresis and anti- CD 20 therapies, aiming to prevent early axonal loss, irreversible comorbidities, and increased mortality in a subacute- onset chronic neuropathy.
2026-07-25 | Serum PLA2R-negative, biopsy-proven PLA2R-positive primary membranous nephropathy in a dichorionic-diamniotic twin pregnancy.
Primary membranous nephropathy (PMN) in pregnancy is rare and poses significant risks including pre-eclampsia, preterm delivery, low birth weight and fetal death. Anti-phospholipase A2 receptor (PLA2R) antibodies are used to confirm diagnosis.We report a case of biopsy-confirmed PLA2R-positive but seronegative PMN in a woman in her late 20s with a dichorionic-diamniotic twin pregnancy. Initial hypoalbuminaemia was attributed to intercurrent infection but was later recognised as nephrotic syndrome at 20+6 weeks gestation. Renal biopsy at 21 weeks confirmed PMN with positive PLA2R and IgG4 staining, despite negative serum PLA2R antibodies.She was managed with tacrolimus and rituximab, with close monitoring and delivered viable twins via emergency caesarean at 33+3 weeks following premature rupture of membranes. Both maternal disease and neonatal outcomes were favourable. This case highlights the challenges in diagnosing and managing seronegative PMN during pregnancy and supports the role of renal biopsy and rituximab in selected patients.
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Drug Discovery Landscape
12 orphan drug designations for Primary membranous glomerulonephritis.
12 orphan drug designations for Primary membranous glomerulonephritis.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Povetacicept | antibodies | EMA | 2026-02-23 | — | Vertex Pharmaceuticals (Ireland) Limited |
povetacicept | proteins | FDA | 2026-01-22 | — | Vertex Pharmaceuticals Incorporated |
Felzartamab | antibodies | EMA | 2025-11-21 | — | Biogen Netherlands B.V. |
zanubrutinib | small molecules | FDA | 2024-05-20 | — | BeOne Medicines USA, Inc. |
Rituximab | antibodies | EMA | 2023-07-25 | — | 4p-Pharma |
Corticotropin (ACTH) porcine (synthetic) | proteins | FDA | 2023-06-21 | — | Cerium Pharmaceuticals, Inc. |
felzartamab | antibodies | FDA | 2023-05-17 | — | Human Immunology Biosciences |
rituximab | antibodies | FDA | 2023-01-26 | — | Mabion S.A. |
Budoprutug | antibodies | FDA | 2023-01-12 | — | Climb Bio, Inc. |
Mizoribine | small molecules | FDA | 2020-11-09 | — | RNR BioMedical Inc. |
obinutuzumab | antibodies | FDA | 2020-06-08 | — | Genentech, Inc., A Member of the Roche Group |
eculizumab | antibodies | FDA | 2001-03-05 | — | Alexion Pharmaceuticals, Inc. |
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