Rashid R, Shrestha RH, Elahi T, Shakeel S, Mubarak M. Immunofluorescence-based reclassification of idiopathic membranoproliferative glomerulonephritis: Insights from a single-center cohort. World J Nephrol 2026; 15(3): 121887 [DOI: 10.5527/wjn.121887]
Corresponding Author of This Article
Muhammed Mubarak, Department of Histopathology, Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi 74200, Sindh, Pakistan. drmubaraksiut@yahoo.com
Research Domain of This Article
Urology & Nephrology
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research-article
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World J Nephrol. Sep 25, 2026; 15(3): 121887 Published online Sep 25, 2026. doi: 10.5527/wjn.121887
Immunofluorescence-based reclassification of idiopathic membranoproliferative glomerulonephritis: Insights from a single-center cohort
Rahma Rashid, Ranil H Shrestha, Tabassum Elahi, Shaheera Shakeel, Muhammed Mubarak
Rahma Rashid, Shaheera Shakeel, Muhammed Mubarak, Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
Ranil H Shrestha, Tabassum Elahi, Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi 74200, Sindh, Pakistan
Author contributions: Rashid R wrote the manuscript with input from all authors; Rashid R and Shrestha RH performed the experiments and analyzed the data; Rashid R and Mubarak M designed the study; Shakeel S and Mubarak M contributed to the interpretation of the results; Elahi T and Mubarak M provided critical feedback and helped shape the research, analysis, and manuscript; Mubarak M supervised the project and critically revised and finalized the draft. All authors were involved in the conceptualization, development of the article and approved the final manuscript.
AI contribution statement: Grammarly (https://app.grammarly.com) was used to improve the grammar and clarity. No other AI tools were used. The authors take full responsibility and accountability for all content of this manuscript, including any portions for which AI tools were used as assistive technologies. All AI-assisted outputs were carefully reviewed, validated, and approved by the authors. AI tools were not used to generate original scientific data, perform independent scientific analyses, or draw scientific conclusions.
Institutional review board statement: The study was approved by the Institutional Ethical Review Committee of the Sindh Institute of Urology and Transplantation, Karachi, Pakistan (Approval No. SIUT-ERC-2022/A-393).
Informed consent statement: All study participants, or their legal guardians, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The dataset and related documents are available from the corresponding author.
Corresponding author: Muhammed Mubarak, Department of Histopathology, Sindh Institute of Urology and Transplantation, Chand Bibi Road, Karachi 74200, Sindh, Pakistan. drmubaraksiut@yahoo.com
Received: April 3, 2026 Revised: June 5, 2026 Accepted: June 24, 2026 Published online: September 25, 2026 Processing time: 132 Days and 4.1 Hours
Abstract
BACKGROUND
Membranoproliferative glomerulonephritis (MPGN) is a rare form of glomerular injury with variable prognosis, defined by immunoglobulin and/or complement deposits in the mesangium and basement membranes on immunofluorescence microscopy.
AIM
To categorize it into immune complex-mediated MPGN (IC-MPGN) or complement-mediated MPGN (C-MPGN) types and to evaluate the clinical significance of this classification.
METHODS
This retrospective cohort study evaluated biopsy-confirmed primary MPGN cases in adults diagnosed between January 2010 and December 2021 at the Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan. Patients were followed for at least 36 months post-biopsy, and secondary causes were excluded. Based on immunofluorescence microscopy findings, cases were categorized as IC-MPGN or C-MPGN. Clinicopathological features and renal outcomes were compared between the two groups.
RESULTS
A total of 128 patients with primary MPGN were included, of whom 100 (78.1%) were reclassified as IC-MPGN and 28 (21.9%) as C-MPGN. No statistically significant differences were observed between the groups in gender distribution, clinical presentation, biopsy indications, histopathological findings, or renal function at diagnosis, except for a modest age difference (median 33.5 years vs 38 years, P = 0.029). Vascular pathology was significantly more frequent in C-MPGN, and C3 deposition was stronger and serum C3 levels lower, consistent with complement consumption. Immunosuppressive therapy was administered to 51 (51%) IC-MPGN patients and 19 (67.8%) C-MPGN patients. At 36 months, IC-MPGN patients showed numerically higher rates of complete or partial remission (62% vs 60.7%), though this difference did not reach statistical significance (log-rank test: P = 0.40). Progression to end-stage kidney disease and dialysis dependence was comparable between the two groups.
CONCLUSION
The majority of MPGN cases were reclassified as IC-MPGN, which showed numerically higher remission rates. Overall, the clinicopathological features at diagnosis were similar between the two groups, though C-MPGN, a less frequent subtype, was associated with vascular pathology and stronger complement deposition, and a poorer medium-term prognosis.
Core Tip: Careful subclassification of membranoproliferative glomerulonephritis (MPGN) using immunofluorescence is essential, as immune complex-mediated MPGN and complement-mediated MPGN (C-MPGN) types differ in underlying mechanisms and outcomes. Although clinical and histopathological features at presentation may appear similar, subtle distinctions, such as stronger C3 deposition and lower serum C3 in C-MPGN, may provide a clue for accurate diagnosis. Immune complex-mediated MPGN is more common and tends to achieve higher remission rates, while C-MPGN may carry a poorer prognosis despite comparable progression to end-stage kidney disease. Long-term follow-up and tailored immunosuppressive strategies are critical for both subtypes to optimize renal outcomes and better understand disease trajectories in diverse populations.
