Kidney Week

Abstract: SA-PO0744

Potential Benefit of Clone-Directed Therapy in C3 Glomerulonephritis Associated with Monoclonal Gammopathy of Undetermined Significance (MGUS) Despite Unresolved Mechanistic Pathways

Session Information

• Glomerular Diseases: Complement-Mediated Glomerulopathies and Infection-Related GN
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Sakai, Kaoru, Kitami Sekijuji Byoin, Kitami, Hokkaido Prefecture, Japan

Kaoru Sakai, MD

• Hashiguchi, Junichi, Kitami Sekijuji Byoin, Kitami, Hokkaido Prefecture, Japan

Junichi Hashiguchi

• Yanai, Mitsuru, Sapporo Tokushukai Byoin, Sapporo, Hokkaido Prefecture, Japan

Mitsuru Yanai, MD, PhD

• Ogawa, Yayoi, Sapporo Tokushukai Byoin, Sapporo, Hokkaido Prefecture, Japan

Yayoi Ogawa, MD, PhD

• Nishio, Saori, Hokkaido Daigaku, Sapporo, Hokkaido Prefecture, Japan

Saori Nishio, MD, PhD

• Mizuno, Masashi, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Masashi Mizuno, MD, PhD

Introduction

C3 glomerulonephritis (C3GN) is characterized by dysregulation of the alternative complement pathway. Monoclonal gammopathy has been implicated as a potential driver of complement activation in some cases. We report a patient with C3GN associated with MGUS who achieved dialysis independence following clone directed therapy.

Case Description

A woman in her 70s presented in year X–1 with progressive renal dysfunction (eGFR 26.3 mL/min/1.73 m²), proteinuria (3.3 g/gCr). Serum M protein (IgG κ), urinary Bence Jones protein (IgG κ), and an elevated free light chain (FLC) κ/λ ratio were detected, while bone marrow plasma cells accounted for only 3%, consistent with MGUS. Renal function further declined (eGFR 20.5 mL/min/1.73 m²), prompting kidney biopsy. Immunofluorescence revealed isolated C3 mesangial deposition, and electron microscopy showed no intramembranous sausage shaped deposits, confirming C3GN. Laboratory testing demonstrated hypocomplementemia, reduced factor H, and anti factor H antibodies, suggesting autoantibody mediated alternative pathway activation. Hemodialysis was initiated for end stage kidney disease in September. Clone directed therapy (daratumumab, bortezomib, and dexamethasone) for presumed MGRS was started in November with the goal of renal recovery. FLC κ levels decreased, complement levels improved, and the patient was successfully weaned off dialysis in February of year X.

Discussion

Although the precise mechanism by which clone directed therapy ameliorates alternative complement pathway activation remains unclear, the temporal association between hematologic response, complement normalization, and renal recovery suggests a potential pathogenic link. Further investigation is warranted to clarify whether monoclonal immunoglobulin directly contributes to complement dysregulation. This case suggests that, despite unresolved mechanistic questions, close collaboration between hematologists and nephrologists might allow clone directed therapy to be a meaningful therapeutic option for C3GN associated with MGUS, even after progression to dialysis dependence.