RARE DISEASE
Immunoglobulin-mediated membranoproliferative glomerulonephritis
Immunoglobulin-mediated membranoproliferative glomerulonephritis
Immunoglobulin-mediated membranoproliferative glomerulonephritis
Synonyms: Ig-mediated MPGN, Ig-mediated membranoproliferative glomerulonephritis, Immunoglobulin-mediated MPGN
Synonyms: Ig-mediated MPGN, Ig-mediated membranoproliferative glomerulonephritis, Immunoglobulin-mediated MPGN
Synonyms: Ig-mediated MPGN, Ig-mediated membranoproliferative glomerulonephritis, Immunoglobulin-mediated MPGN
Drug discovery
2
drugs
With orphan designations
Overview
Immunoglobulin-mediated membranoproliferative glomerulonephritis (Ig-MPGN) is a rare glomerular disease characterized by immune complex deposition in glomeruli, activating classical complement pathways. Histopathology reveals hypercellularity, glomerular basement membrane thickening, and immunoglobulin/complement deposits (C3, IgG) on immunofluorescence [1][2][6]. Clinical presentation ranges from asymptomatic proteinuria/hematuria to nephrotic syndrome (edema, hypoalbuminemia) and acute kidney injury [2][3]. Secondary causes include infections (hepatitis B/C), autoimmune diseases (lupus), and monoclonal gammopathies [1][6]. Diagnosis requires renal biopsy with specialist evaluation [3]. Treatment combines immunosuppression (corticosteroids, mycophenolate) and renin-angiotensin system (RAS) inhibitors, though prognosis remains guarded [8][12].
Categories: rare genetic diseases, rare renal diseases, rare transplant-related disorders
Research Papers
52 drug discovery papers about Immunoglobulin-mediated membranoproliferative glomerulonephritis, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
52 drug discovery papers about Immunoglobulin-mediated membranoproliferative glomerulonephritis, with 1 first-in-class and 1 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2024-10-01 | Successful Management of Membranoproliferative Glomerulonephritis with Repository Corticotropin Injection
Introduction: Membranoproliferative glomerulonephritis (MPGN) is a pattern of glomerular injury subdivided by light microscopy into immune complex/monoclonal immunoglobulin-mediated, complement-mediated, and MPGN without immunoglobulin or complement deposition. Treating underlying causes is ideal, but idiopathic immune complex MPGN is often managed with immunosuppressive medications. Repository corticotropin injection shows promise in hard-to-treat cases, as illustrated in a successful treatment involving significant psychiatric side effects from steroids. Case Description: A 30-year-old female with MPGN diagnosed at age 16, presented to hospital with lower extremity edema and AKI. Before the presentation she was treated with prednisone 20 mg daily for many years and any attempt to taper prednisone resulted in MPGN flares. She was previously also trialed on mycophenolate with lower dose prednisone, but gastrointestinal side effects led to discontinuation of mycophenolate. She was then treated with repository corticotropin injection with prednisone 5 mg and was stable for two years until she had another flare with urine protein creatinine ratio (UPCR) rising to 3.2 g/g. Increasing prednisone to 50 mg/day temporarily improved UPCR, but severe depression with suicidal ideation prompted cessation of steroids. Subsequently, her renal function declined, with creatinine rising and UPCR reaching 4 g/g. After discontinuing all her medications for six months, severe deterioration ensued, with creatinine at 3.19 and UPCR at 12 g/g. She was admitted to hospital and renal biopsy was done which showed MPGN immune complex. Despite induction therapy with cyclophosphamide and rituximab her UPCR remained at 8.5 g/g after three months. Repository corticotropin injection was initiated at 80 mg biweekly, reducing UPCR to 4.35 g/g in a month and further to 0.75 g/g over three months. Discussion: Our case of difficult-to-treat idiopathic immune complex MPGN responded only to high steroid doses, which were discontinued due to steroid-induced suicidal ideation. Repository corticotropin injection, which stimulates endogenous steroid production, offered lower steroid exposure and fewer side effects. This may be a good option to avoid systemic side effects of steroids in other hard to treat cases.
2022-05-01 | Treatment with bortezomib for recurrent proliferative glomerulonephritis with monoclonal IgG deposits in kidney allograft. Case report and review of the literature
Abstract Proliferative glomerulonephritis with monoclonal immunoglobulin IgG deposits (PGNMID) is an already described form of renal involvement by monoclonal gammopathy. PGNMID is known to recur in kidney allografts. Bortezomib has shown clinical success in the treatment of multiple myeloma. However, its effect for recurrent PGNMID in kidney allografts has rarely been reported. We present the case of a 61-year-old woman who developed recurrent PGNMID 3 weeks after kidney transplantation. This patient was initially treated with steroid pulses (500 mg/day for 2 days) and two cycles of rituximab therapy (200 mg/body). However, disease progression was observed with mesangial matrix expansion and subendothelial deposits by light microscopy and stronger staining for IgG3 and kappa in the mesangial area by Immunofluorescence (IF) microscopy. Thus, we started treatment with bortezomib therapy (1.3 mg/m2, once weekly, on days 1, 8, 15, and 22 in a 5-week cycle, for a total of six cycles). Bortezomib therapy reduced massive proteinuria, although monoclonal immune deposits on IF and the serum creatinine level did not change during the treatment period. Seven months after completion of the first bortezomib course, we decided to prescribe a second course of bortezomib with the same regimen. Each course resulted in a > 50% reduction of proteinuria. Bortezomib may delay the progress of PGNMID in kidney allograft patients.
2020-03-01 | Rituximab use in adult glomerulopathies and its rationale
Abstract Glomerulopathies are one of the leading causes of end-stage renal disease. In the last years, clinical research has made significant contributions to the understanding of such conditions. Recently, rituximab (RTX) has appeared as a reasonably safe treatment. The Kidney Disease: Improving Global Outcomes guidelines (KDIGO) recommended RTX only as initial treatment in antineutrophil cytoplasm antibody associated vasculitis (AAV) and in non-responders patients with lupus nephritis (LN), but these guidelines have not been updated since 2012. Nowadays, RTX seems to be at least as effective as other immunosuppressive regimens in idiopathic membranous nephropathy (IMN). In minimal-change disease, (MCD) this drug might allow a long-lasting remission period in steroid-dependent or frequently relapsing patients. Preliminary results support the use of RTX in patients with pure membranous LN and immunoglobulin-mediated membranoproliferative glomerulonephritis (MPGN), but not in patients with class III/IV LN or complement-mediated MPGN. No conclusion can be drawn in idiopathic focal segmental glomerulosclerosis (FSGS) and anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM GN) because studies are small, heterogeneous, and scarce. Lastly, immunosuppression including RTX is not particularly useful in IgA nephropathy. This review presents the general background, outcomes, and safety for RTX treatment in different glomerulopathies. In this regard, we describe randomized controlled trials (RCTs) performed in adults, whenever possible. A literature search was performed using clinicaltrials.gov and PubMed.
2019-06-01 | Recurrent membranoproliferative glomerulonephritis in a renal transplant secondary to monoclonal gammopathy of renal significance successfully treated with bortezomib
Internal Medicine JournalVolume 49, Issue 6 p. 801-802 Letters to the Editor Recurrent membranoproliferative glomerulonephritis in a renal transplant secondary to monoclonal gammopathy of renal significance successfully treated with bortezomib Ke Li Chow, Ke Li Chow orcid.org/0000-0002-4589-0735 Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorJohn Kanellis, John Kanellis Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorSukhpal Dayan, Sukhpal Dayan Department of Pathology, Monash Medical Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorJessica Ryan, Jessica Ryan Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, Australia Department of Medicine, Monash University, Melbourne, Victoria, AustraliaSearch for more papers by this author Ke Li Chow, Ke Li Chow orcid.org/0000-0002-4589-0735 Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorJohn Kanellis, John Kanellis Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorSukhpal Dayan, Sukhpal Dayan Department of Pathology, Monash Medical Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorJessica Ryan, Jessica Ryan Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, Australia Department of Medicine, Monash University, Melbourne, Victoria, AustraliaSearch for more papers by this author First published: 11 June 2019 https://doi.org/10.1111/imj.14313Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume49, Issue6June 2019Pages 801-802 RelatedInformation
2019-02-14 | Complete biopsy-proven resolution of deposits in recurrent proliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) following rituximab treatment in renal allograft
Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) is a disease entity classified under the group of "Monoclonal gammopathy-related kidney diseases", and can recur after transplant. Clinical remission of proteinuria in patients with PGNMIGD has been previously shown following anti-B cell and/or anti-plasma cell therapies. Our case is the first to show complete histologic resolution of the glomerular monoclonal IgG kappa deposits in a case of recurrent PGNMIGD in renal allograft after rituximab and steroid treatment. This is a novel finding and it shows that the deposits are amenable to therapy. This case also highlights the importance of IgG subclass staining in the recognition of the monoclonal nature of the deposits. It is particularly important in PGNMIGD because only 20 to 30% of patients with this disease are reported to have detectable monoclonal gammopathy, and the deposits do not have any organized substructure on electron microscopic examination. Morphologically, they resemble polyclonal immune-type deposits seen in other immune complex glomerulonephritides such as lupus nephritis, infection-associated glomerulonephritis, and membranoproliferative glomerulonephritis (MPGN type I). The patient is a 44 year old Caucasian male who received a living unrelated donor kidney transplant for end-stage renal disease diagnosed 7 years before transplant. The reported native kidney biopsy diagnosis was membranoproliferative glomerulonephritis (MPGN) with IgG, C3 and kappa restricted deposits. Fourteen months post-transplant, he presented with abrupt worsening of graft function, proteinuria and serum IgG kappa monoclonal spike. Allograft biopsy was consistent with recurrent PGNMIGD, considering the native kidney diagnosis and interval post-transplant. He underwent plasmapheresis, IV pooled immune globulin, steroid pulse and taper, and anti-CD-20 Rituximab therapy. Patient had gradual decline in proteinuria and complete resolution of the immune deposits on repeat biopsy 3 months later. Unfortunately he subsequently developed chronic antibody-mediated rejection and transplant glomerulopathy and graft failure 34 months post-transplant. In a transplant setting, repeat allograft biopsies are frequently performed for graft dysfunction. This provides a good opportunity to study the evolution of the immune deposits following treatment. Our case shows complete histologic resolution of the deposits in allograft PGNMIGD.
2024-10-01 | Successful Management of Membranoproliferative Glomerulonephritis with Repository Corticotropin Injection
Introduction: Membranoproliferative glomerulonephritis (MPGN) is a pattern of glomerular injury subdivided by light microscopy into immune complex/monoclonal immunoglobulin-mediated, complement-mediated, and MPGN without immunoglobulin or complement deposition. Treating underlying causes is ideal, but idiopathic immune complex MPGN is often managed with immunosuppressive medications. Repository corticotropin injection shows promise in hard-to-treat cases, as illustrated in a successful treatment involving significant psychiatric side effects from steroids. Case Description: A 30-year-old female with MPGN diagnosed at age 16, presented to hospital with lower extremity edema and AKI. Before the presentation she was treated with prednisone 20 mg daily for many years and any attempt to taper prednisone resulted in MPGN flares. She was previously also trialed on mycophenolate with lower dose prednisone, but gastrointestinal side effects led to discontinuation of mycophenolate. She was then treated with repository corticotropin injection with prednisone 5 mg and was stable for two years until she had another flare with urine protein creatinine ratio (UPCR) rising to 3.2 g/g. Increasing prednisone to 50 mg/day temporarily improved UPCR, but severe depression with suicidal ideation prompted cessation of steroids. Subsequently, her renal function declined, with creatinine rising and UPCR reaching 4 g/g. After discontinuing all her medications for six months, severe deterioration ensued, with creatinine at 3.19 and UPCR at 12 g/g. She was admitted to hospital and renal biopsy was done which showed MPGN immune complex. Despite induction therapy with cyclophosphamide and rituximab her UPCR remained at 8.5 g/g after three months. Repository corticotropin injection was initiated at 80 mg biweekly, reducing UPCR to 4.35 g/g in a month and further to 0.75 g/g over three months. Discussion: Our case of difficult-to-treat idiopathic immune complex MPGN responded only to high steroid doses, which were discontinued due to steroid-induced suicidal ideation. Repository corticotropin injection, which stimulates endogenous steroid production, offered lower steroid exposure and fewer side effects. This may be a good option to avoid systemic side effects of steroids in other hard to treat cases.
2022-05-01 | Treatment with bortezomib for recurrent proliferative glomerulonephritis with monoclonal IgG deposits in kidney allograft. Case report and review of the literature
Abstract Proliferative glomerulonephritis with monoclonal immunoglobulin IgG deposits (PGNMID) is an already described form of renal involvement by monoclonal gammopathy. PGNMID is known to recur in kidney allografts. Bortezomib has shown clinical success in the treatment of multiple myeloma. However, its effect for recurrent PGNMID in kidney allografts has rarely been reported. We present the case of a 61-year-old woman who developed recurrent PGNMID 3 weeks after kidney transplantation. This patient was initially treated with steroid pulses (500 mg/day for 2 days) and two cycles of rituximab therapy (200 mg/body). However, disease progression was observed with mesangial matrix expansion and subendothelial deposits by light microscopy and stronger staining for IgG3 and kappa in the mesangial area by Immunofluorescence (IF) microscopy. Thus, we started treatment with bortezomib therapy (1.3 mg/m2, once weekly, on days 1, 8, 15, and 22 in a 5-week cycle, for a total of six cycles). Bortezomib therapy reduced massive proteinuria, although monoclonal immune deposits on IF and the serum creatinine level did not change during the treatment period. Seven months after completion of the first bortezomib course, we decided to prescribe a second course of bortezomib with the same regimen. Each course resulted in a > 50% reduction of proteinuria. Bortezomib may delay the progress of PGNMID in kidney allograft patients.
2020-03-01 | Rituximab use in adult glomerulopathies and its rationale
Abstract Glomerulopathies are one of the leading causes of end-stage renal disease. In the last years, clinical research has made significant contributions to the understanding of such conditions. Recently, rituximab (RTX) has appeared as a reasonably safe treatment. The Kidney Disease: Improving Global Outcomes guidelines (KDIGO) recommended RTX only as initial treatment in antineutrophil cytoplasm antibody associated vasculitis (AAV) and in non-responders patients with lupus nephritis (LN), but these guidelines have not been updated since 2012. Nowadays, RTX seems to be at least as effective as other immunosuppressive regimens in idiopathic membranous nephropathy (IMN). In minimal-change disease, (MCD) this drug might allow a long-lasting remission period in steroid-dependent or frequently relapsing patients. Preliminary results support the use of RTX in patients with pure membranous LN and immunoglobulin-mediated membranoproliferative glomerulonephritis (MPGN), but not in patients with class III/IV LN or complement-mediated MPGN. No conclusion can be drawn in idiopathic focal segmental glomerulosclerosis (FSGS) and anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM GN) because studies are small, heterogeneous, and scarce. Lastly, immunosuppression including RTX is not particularly useful in IgA nephropathy. This review presents the general background, outcomes, and safety for RTX treatment in different glomerulopathies. In this regard, we describe randomized controlled trials (RCTs) performed in adults, whenever possible. A literature search was performed using clinicaltrials.gov and PubMed.
2019-06-01 | Recurrent membranoproliferative glomerulonephritis in a renal transplant secondary to monoclonal gammopathy of renal significance successfully treated with bortezomib
Internal Medicine JournalVolume 49, Issue 6 p. 801-802 Letters to the Editor Recurrent membranoproliferative glomerulonephritis in a renal transplant secondary to monoclonal gammopathy of renal significance successfully treated with bortezomib Ke Li Chow, Ke Li Chow orcid.org/0000-0002-4589-0735 Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorJohn Kanellis, John Kanellis Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorSukhpal Dayan, Sukhpal Dayan Department of Pathology, Monash Medical Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorJessica Ryan, Jessica Ryan Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, Australia Department of Medicine, Monash University, Melbourne, Victoria, AustraliaSearch for more papers by this author Ke Li Chow, Ke Li Chow orcid.org/0000-0002-4589-0735 Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorJohn Kanellis, John Kanellis Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorSukhpal Dayan, Sukhpal Dayan Department of Pathology, Monash Medical Centre, Melbourne, Victoria, AustraliaSearch for more papers by this authorJessica Ryan, Jessica Ryan Department of Nephrology, Monash Medical Centre, Melbourne, Victoria, Australia Department of Medicine, Monash University, Melbourne, Victoria, AustraliaSearch for more papers by this author First published: 11 June 2019 https://doi.org/10.1111/imj.14313Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume49, Issue6June 2019Pages 801-802 RelatedInformation
2019-02-14 | Complete biopsy-proven resolution of deposits in recurrent proliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) following rituximab treatment in renal allograft
Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMIGD) is a disease entity classified under the group of "Monoclonal gammopathy-related kidney diseases", and can recur after transplant. Clinical remission of proteinuria in patients with PGNMIGD has been previously shown following anti-B cell and/or anti-plasma cell therapies. Our case is the first to show complete histologic resolution of the glomerular monoclonal IgG kappa deposits in a case of recurrent PGNMIGD in renal allograft after rituximab and steroid treatment. This is a novel finding and it shows that the deposits are amenable to therapy. This case also highlights the importance of IgG subclass staining in the recognition of the monoclonal nature of the deposits. It is particularly important in PGNMIGD because only 20 to 30% of patients with this disease are reported to have detectable monoclonal gammopathy, and the deposits do not have any organized substructure on electron microscopic examination. Morphologically, they resemble polyclonal immune-type deposits seen in other immune complex glomerulonephritides such as lupus nephritis, infection-associated glomerulonephritis, and membranoproliferative glomerulonephritis (MPGN type I). The patient is a 44 year old Caucasian male who received a living unrelated donor kidney transplant for end-stage renal disease diagnosed 7 years before transplant. The reported native kidney biopsy diagnosis was membranoproliferative glomerulonephritis (MPGN) with IgG, C3 and kappa restricted deposits. Fourteen months post-transplant, he presented with abrupt worsening of graft function, proteinuria and serum IgG kappa monoclonal spike. Allograft biopsy was consistent with recurrent PGNMIGD, considering the native kidney diagnosis and interval post-transplant. He underwent plasmapheresis, IV pooled immune globulin, steroid pulse and taper, and anti-CD-20 Rituximab therapy. Patient had gradual decline in proteinuria and complete resolution of the immune deposits on repeat biopsy 3 months later. Unfortunately he subsequently developed chronic antibody-mediated rejection and transplant glomerulopathy and graft failure 34 months post-transplant. In a transplant setting, repeat allograft biopsies are frequently performed for graft dysfunction. This provides a good opportunity to study the evolution of the immune deposits following treatment. Our case shows complete histologic resolution of the deposits in allograft PGNMIGD.
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Drug Discovery Landscape
2 orphan drug designations for Immunoglobulin-mediated membranoproliferative glomerulonephritis, including 1 approved therapy.
2 orphan drug designations for Immunoglobulin-mediated membranoproliferative glomerulonephritis, including 1 approved therapy.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
a chemically synthesized double-stranded oligonucleotide directed against C3 messenger RNA | RNAs | FDA | 2026-02-23 | — | Sanegene Bio USA Inc. |
pegcetacoplan [Empaveli] | antibodies | FDA | 2022-06-07 | 2025-07-28 | Apellis Pharmaceuticals, Inc. |
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