Abstract: PUB139
Evolving Clinicopathologic Features in Glomerular Diseases: From C3-Dominant Glomerulonephritis to Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits
Session Information
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Caparali, Emine Bilge, The University of Texas Southwestern Medical Center Department of Internal Medicine, Dallas, Texas, United States
- Baloch, Ayesha Khan, Shifa College of Medicine, Islamabad, Islamabad Capital Territory, Pakistan
- Saxena, Ramesh, The University of Texas Southwestern Medical Center Department of Internal Medicine, Dallas, Texas, United States
Introduction
C3 glomerulonephritis (C3GN), post-infectious glomerulonephritis (PIGN), IgA nephropathy (IgAN), and proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) are distinct entities with different pathogenic mechanisms. We present a case in which an initial diagnosis of C3GN was later followed by findings consistent with PGNMID.
Case Description
A 55-year-old male developed gross hematuria in 2018 after a respiratory illness, recurrent hematuria with flu-like symptoms after Zoster vaccine in 2019, followed by proteinuria in 2020. Kidney biopsy showed mesangial hypercellularity with C3-dominant deposits (2-fold >IgA). Alternative complement pathway evaluation was unrevealing. He achieved complete remission with conservative measures.
In 2022, he had recurrent gross hematuria and proteinuria after COVID-19 vaccine. Biopsy revealed predominant IgA deposits over C3, along with IgM, C1q, and 4+ kappa restriction, suggesting PGNMID. Workup for plasma cell dyscrasia was negative. He was treated with daratumumab/dexamethasone with initial improvement, followed by uptrending creatinine and proteinuria. The biopsy in 2025 confirmed persistent PGNMID with IgA kappa and worsening fibrosis. He was switched to cyclophosphamide/bortezomib/dexamethasone with limited response, and then to Elranatamab, but he progressed to end-stage renal disease (ESRD).
Discussion
Although the initial biopsy was reported as C3GN due to dominant C3 staining, IgA deposits were present and alternative complement pathway testing was negative, making IgAN with prominent C3 deposition an alternative diagnosis. Given preceding respiratory illness, resolving PIGN is also plausible, as C3 staining may predominate during later phases.
Similarly, while the 2022 biopsy favored PGNMID due to IgA with kappa restriction, the absence of a detectable B-cell clone raises the possibility of monotypic rather than monoclonal IgA deposition, making definite monoclonal gammopathy of renal significance (MGRS) less certain.
This case highlights the importance of repeat biopsy, pathologic reinterpretation, and maintaining a broad differential in recurrent hematuria and proteinuria.