Kidney Week

Abstract: SA-PO0738

Long-Term Eculizumab Treatment Failure in C3 Glomerulonephritis: Effect of Persistent Upstream Complement Activation

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

• Zubidat, Dalia, Mayo Clinic Research Rochester, Rochester, Minnesota, United States

Dalia Zubidat, MD

• Soler, Maria Jose, Hospital Universitari Vall d'Hebron, Barcelona, CT, Spain

Maria Jose Soler, MD, PhD

• Cara, Anila, Mayo Clinic Research Rochester, Rochester, Minnesota, United States

Anila Cara, MD

• Sethi, Sanjeev, Mayo Clinic Research Rochester, Rochester, Minnesota, United States

Sanjeev Sethi, MD, PhD

• Appel, Gerald B., Columbia University, New York, New York, United States

Gerald B. Appel, MD, FASN

• Santoriello, Dominick, Columbia University, New York, New York, United States

Dominick Santoriello, MD

• Dos Santos, Fernanda Geremias, Mayo Clinic Research Rochester, Rochester, Minnesota, United States

Fernanda Geremias Dos Santos, MD

• Fervenza, Fernando C., Mayo Clinic Research Rochester, Rochester, Minnesota, United States

Fernando C. Fervenza, MD, PhD, FASN

Introduction

C3 glomerulonephritis (C3GN) is driven by dysregulation of the alternative complement pathway. Eculizumab, a monoclonal antibody targeting C5, has shown variable efficacy but long-term outcomes remain unknown.

Case Description

Two patients with C3GN who failed multiple immunosuppressive therapies and were subsequently treated with eculizumab.
Case 1, 20-year-old women with progressive kidney dysfunction and nephrotic-range proteinuria despite corticosteroids and mycophenolate mofetil, was started on eculizumab. Initial and transient improvement in kidney function and proteinuria was noted at 6 months; however, this response was not sustained, and patient progressed to ESKD despite eculizumab therapy in 1year.
Case 2, 32-year-old women with longstanding proteinuria and genetically and serologically confirmed complement dysregulation, also demonstrated initial stabilization of kidney function and reduction in proteinuria with eculizumab. However, despite long treatment with eculizumab, kidney function progressively declined, ultimately requiring kidney transplantation, after 5 years of therapy.
In both cases, repeat kidney biopsies during eculizumab therapy showed persistent strong C3 deposition along the mesangium and capillary walls, indicating ongoing complement activation upstream of C5 inhibition.

Discussion

These cases highlight the limited long-term efficacy of terminal complement blockade in C3GN. While eculizumab may provide transient clinical benefit, persistent upstream complement activation with continued C3 deposition appears to drive ongoing disease progression. These findings support the emerging therapeutic strategy of targeting proximal complement components and underscore the need for individualized, mechanism-based treatment approaches in C3 glomerulopathy.