Kidney Week

Abstract: SA-PO0743

Improvement in eGFR Slope with Iptacopan in C3 Glomerulonephritis with Complement Factor B Variant

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

• Matsumura, Hideki, Osaka Ika Yakka Daigaku, Takatsuki, Osaka Prefecture, Japan

Hideki Matsumura, MD, PhD

• Fujii, Yuko, Osaka Ika Yakka Daigaku, Takatsuki, Osaka Prefecture, Japan

Yuko Fujii, MD, PhD

• Tanaka, Tomoko, Osaka Ika Yakka Daigaku, Takatsuki, Osaka Prefecture, Japan

Tomoko Tanaka

• Yamazaki, Satoshi, Amanokawa Byoin, Hirakata, Osaka Prefecture, Japan

Satoshi Yamazaki

• Shirasu, Akihiko, Shiritsu Hirakata Byoin, Hirakata, Osaka Prefecture, Japan

Akihiko Shirasu, MD

• Nakakura, Hyogo, Amanokawa Byoin, Hirakata, Osaka Prefecture, Japan

Hyogo Nakakura

• Ashida, Akira, Osaka Ika Yakka Daigaku, Takatsuki, Osaka Prefecture, Japan

Akira Ashida, MD, PhD

Introduction

C3 glomerulonephritis (C3GN) results from dysregulation of the alternative complement pathway and lacks established therapy. Iptacopan, an oral factor B inhibitor, has emerged as a targeted treatment, but evidence in genetically defined C3GN is limited. We report a refractory case with a complement factor B (CFB) mutation that showed improved complement activity and a favorable trajectory of kidney function after iptacopan.

Case Description

An 18-year-old female was diagnosed with C3GN at age 10 with hematuria, proteinuria, and hypocomplementemia. Kidney biopsy showed a membranoproliferative pattern with dominant C3 deposition and mesangial and subendothelial electron-dense deposits without dense intramembranous deposits. Despite treatment with angiotensin-converting enzyme inhibitors, corticosteroids, and mycophenolate mofetil, nephrotic-range proteinuria persisted.
Genetic analysis identified a CFB mutation (c.1186G>A). LDL apheresis temporarily reduced proteinuria; however, relapse occurred, followed by a progressive decline in kidney function.
Before iptacopan, eGFR declined from approximately 106 to 80 mL/min/1.73 m² over one year (slope −33.2 mL/min/1.73 m²/year). After treatment, serum C3 increased from 6 to 39 mg/dL, with a 23% reduction in proteinuria and improved hypoalbuminemia. The eGFR slope improved to +5.8 mL/min/1.73 m²/year.

Discussion

Iptacopan restored complement activity and improved the trajectory of kidney function in C3GN with a CFB mutation. The marked change in eGFR slope suggests a disease-modifying effect beyond proteinuria reduction. The concurrent improvement in complement activity and eGFR supports a treatment-related effect rather than spontaneous fluctuation. Given the mechanistic alignment between factor B inhibition and the underlying abnormality, this case supports a precision medicine approach.

Acknowledgment

The authors thank Professor Kandai Nozu and colleagues at the Department of Pediatrics, Kobe University Graduate School of Medicine, for performing the genetic analysis.

Change in eGFR over time before and after initiation of iptacopan. The eGFR slope improved from −33.2 to +5.8 mL/min/1.73 m²/year following treatment, indicating a marked change in kidney function trajectory.