Kidney Week

Abstract: SA-PO0754

Complementing the Path to Chimeric Antigen Receptor (CAR)-T: Pegcetacoplan Rescue in Refractory Lupus Nephritis

Session Information

• Glomerular Diseases: Lupus Nephritis, Monoclonal Gammopathy-Related Disease, and Transplantation
  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

• Kent, Nicole Jami, University of Nebraska Medical Center, Omaha, Nebraska, United States

Nicole Jami Kent, MD

• Grigsby, Jennifer L., University of Nebraska Medical Center, Omaha, Nebraska, United States

Jennifer L. Grigsby, MD

• Foster, Kirk W., University of Nebraska Medical Center, Omaha, Nebraska, United States

Kirk W. Foster, MD

• Medlin, Jennifer, University of Nebraska Medical Center, Omaha, Nebraska, United States

Jennifer Medlin, MD

• Ravipati, Prasanth, University of Nebraska Medical Center, Omaha, Nebraska, United States

Prasanth Ravipati, MD

Introduction

Refractory lupus nephritis (LN) remains a major clinical challenge with limited evidence guiding management after failure of multiple standard-of-care therapies. LN is a heterogenous disease associated with abnormalities of multiple immune pathways including complement dysregulation, which plays a key role in LN pathogenesis. Emergence of complement inhibitors with success in glomerular disease including immune complex glomerulonephritis, supports a potential role of complement blockade in LN. Here, we present a case with the novel use of pegcetacoplan as a bridge to CAR-T cell therapy in LN refractory to 6 previous lines of therapy.

Case Description

A 22-year-old female with biopsy-proven class IV proliferative LN presented for clinic follow up with persistent disease activity, including proteinuria (4.0-6.0 g/g), hypoalbuminemia, and volume overload. Prior treatment included cyclophosphamide, belimumab, prednisone, voclosporin, mycophenolate mofetil, and rituximab. Her renal function was normal by serum creatinine (sCr), 0.6 mg/dL. A repeat kidney biopsy confirmed active class IV LN. Given exhaustion of conventional therapies without meaningful response, complement inhibition with pegcetacoplan was initiated as bridge therapy while the patient was being evaluated for CAR-T cell therapy. After 5 doses of pegcetacoplan (2.5 weeks), the patient demonstrated a notable clinical response: serum albumin rose to 2.9 g/dL from 1.4 g/dL, peripheral edema resolved, serum C3 levels normalized, spot proteinuria decreased from a peak of 6.0 g/g to 2.7 g/g, and renal function remained stable (sCr 0.7 mg/dL). However, the patient continues to have significant lupus disease burden, and evaluation for CAR-T cell therapy is ongoing.

Discussion

This case illustrates the potential role of proximal complement inhibition with pegcetacoplan as a therapy in LN unresponsive to multiple immunosuppressive regimens. The rapid improvement in proteinuria, serum albumin, and complement levels within weeks of initiation suggests that complement-mediated injury is a significant contributor to ongoing disease activity in this setting. Pegcetacoplan’s unique mechanism of action, including its titratable intensity of complement blockade, suggests it may serve as a stabilizing therapeutic or bridge in LN while patients prepare for definitive management. Further investigation is warranted to define the role of complement inhibition in LN.