The Clinical and Pathological Characteristics of Patients with Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits

Introduction: Proliferative glomerulonephritis with monoclonal immunoglobin (Ig) deposits (PGNMID) is a rare form of kidney disease associated with low monoclonal protein detection rates and poor renal outcomes. The lack of effective therapy is partly due to limited data and understanding...

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Main Authors: Tariku T. Gudura, Hanny Sawaf, Randy Ogbenna, Ali Mehdi, Leal Herlitz, Surafel K. Gebreselassie, Shane A. Bobart
Format: Article
Language:English
Published: Karger Publishers 2025-02-01
Series:Glomerular Diseases
Online Access:https://karger.com/article/doi/10.1159/000544864
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author Tariku T. Gudura
Hanny Sawaf
Randy Ogbenna
Ali Mehdi
Leal Herlitz
Surafel K. Gebreselassie
Shane A. Bobart
author_facet Tariku T. Gudura
Hanny Sawaf
Randy Ogbenna
Ali Mehdi
Leal Herlitz
Surafel K. Gebreselassie
Shane A. Bobart
author_sort Tariku T. Gudura
collection DOAJ
description Introduction: Proliferative glomerulonephritis with monoclonal immunoglobin (Ig) deposits (PGNMID) is a rare form of kidney disease associated with low monoclonal protein detection rates and poor renal outcomes. The lack of effective therapy is partly due to limited data and understanding of its pathogenesis. Methods: We conducted a retrospective analysis of 18 patients with PGNMID from the Cleveland Clinic Kidney Biopsy Epidemiology Project from January 2015 to March 2023. Results: PGNMID was more predominant among males (67%), and whites (78%), with median age of 60 years. Over 2/3rd of patients presented with hypertension, renal insufficiency, and hematuria, while 26% of patients had nephrotic syndrome. Mean serum creatinine and proteinuria at biopsy were 3.2 mg/dL and 4.3 g/g, respectively. A detectable monoclonal (M) protein was detected in 28% of cases; however, only 3 patients had underlying hematologic disorders (multiple myeloma, CLL, and B-cell lymphoma). An endocapillary hypercellularity/membranoproliferative pattern (72%), IgG/kappa (83%), and IgG3 (56%) were predominant findings on kidney pathology. Eight patients (44%) progressed to end-stage kidney disease (ESKD), with a median onset of 7.5 months after the initial kidney biopsy. While 6 patients achieved complete remission primarily with clone-directed therapy. Conclusion: Despite monoclonal protein deposition on kidney biopsy, 28% patients with PGNMID had a detectable monoclonal protein. Unlike other forms of paraproteinemic kidney diseases, renal outcomes for patients with PGNMID are poor, with 44% progressing to ESKD (median time 7.5 months) after kidney biopsy in our cohort. Clone-directed therapy to improve outcomes remains the mainstay of treatment, despite the absence of detectable clone in most cases. Thus, further investigation into the pathogenesis of PGNMID is warranted to guide future treatment discovery and clinical trials.
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spelling doaj-art-8dc705157d874253ab0facb71a9061542025-08-20T03:49:41ZengKarger PublishersGlomerular Diseases2673-36332025-02-015114215010.1159/000544864The Clinical and Pathological Characteristics of Patients with Proliferative Glomerulonephritis with Monoclonal Immunoglobulin DepositsTariku T. GuduraHanny SawafRandy OgbennaAli MehdiLeal Herlitzhttps://orcid.org/0000-0003-2665-8559Surafel K. GebreselassieShane A. Bobart Introduction: Proliferative glomerulonephritis with monoclonal immunoglobin (Ig) deposits (PGNMID) is a rare form of kidney disease associated with low monoclonal protein detection rates and poor renal outcomes. The lack of effective therapy is partly due to limited data and understanding of its pathogenesis. Methods: We conducted a retrospective analysis of 18 patients with PGNMID from the Cleveland Clinic Kidney Biopsy Epidemiology Project from January 2015 to March 2023. Results: PGNMID was more predominant among males (67%), and whites (78%), with median age of 60 years. Over 2/3rd of patients presented with hypertension, renal insufficiency, and hematuria, while 26% of patients had nephrotic syndrome. Mean serum creatinine and proteinuria at biopsy were 3.2 mg/dL and 4.3 g/g, respectively. A detectable monoclonal (M) protein was detected in 28% of cases; however, only 3 patients had underlying hematologic disorders (multiple myeloma, CLL, and B-cell lymphoma). An endocapillary hypercellularity/membranoproliferative pattern (72%), IgG/kappa (83%), and IgG3 (56%) were predominant findings on kidney pathology. Eight patients (44%) progressed to end-stage kidney disease (ESKD), with a median onset of 7.5 months after the initial kidney biopsy. While 6 patients achieved complete remission primarily with clone-directed therapy. Conclusion: Despite monoclonal protein deposition on kidney biopsy, 28% patients with PGNMID had a detectable monoclonal protein. Unlike other forms of paraproteinemic kidney diseases, renal outcomes for patients with PGNMID are poor, with 44% progressing to ESKD (median time 7.5 months) after kidney biopsy in our cohort. Clone-directed therapy to improve outcomes remains the mainstay of treatment, despite the absence of detectable clone in most cases. Thus, further investigation into the pathogenesis of PGNMID is warranted to guide future treatment discovery and clinical trials. https://karger.com/article/doi/10.1159/000544864
spellingShingle Tariku T. Gudura
Hanny Sawaf
Randy Ogbenna
Ali Mehdi
Leal Herlitz
Surafel K. Gebreselassie
Shane A. Bobart
The Clinical and Pathological Characteristics of Patients with Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits
Glomerular Diseases
title The Clinical and Pathological Characteristics of Patients with Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits
title_full The Clinical and Pathological Characteristics of Patients with Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits
title_fullStr The Clinical and Pathological Characteristics of Patients with Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits
title_full_unstemmed The Clinical and Pathological Characteristics of Patients with Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits
title_short The Clinical and Pathological Characteristics of Patients with Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits
title_sort clinical and pathological characteristics of patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposits
url https://karger.com/article/doi/10.1159/000544864
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