Kidney Week

Abstract: SA-PO0767

C3 Glomerulonephritis and Evolving Podocytopathy in Lupus: Why Repeat Kidney Biopsy Matters

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

• Aggarwal, Kanika, Temple University Hospital, Philadelphia, Pennsylvania, United States

Kanika Aggarwal, MD

• Patel, Vraj, Temple University Hospital, Philadelphia, Pennsylvania, United States

Vraj Patel, MD

• Graydon, Drew N., Temple University Hospital, Philadelphia, Pennsylvania, United States

Drew N. Graydon, DO

• Hassler, Jared, Temple University Hospital, Philadelphia, Pennsylvania, United States

Jared Hassler, MD

• Koul, Sheetal, Temple University Hospital, Philadelphia, Pennsylvania, United States

Sheetal Koul, MD

• Lee, Iris J., Temple University Hospital, Philadelphia, Pennsylvania, United States

Iris J. Lee, MD

Introduction

A patient with systemic lupus erythematosus (SLE), with worsening proteinuria was found to have C3 glomerulonephritis (C3GN). The etiology of proteinuria was uncertain, and repeat kidney biopsies helped guide management.

Case Description

45-year-old woman with hypertension, SLE (ANA 1:640, dsDNA, Sm/RNP, low complements), presented with new lower extremity edema. Labs revealed nephrotic-range proteinuria (12 g/g), hematuria, low C3 (12 mg/dL), and hypoalbuminemia (2.0 g/dL). Lupus nephritis (LN) was expected, however biopsy showed membranoproliferative GN with C3/IgM deposition consistent with C3GN, and 20–30% IFTA.
She was initially treated with mycophenolic acid and prednisone, achieving ~50% reduction in proteinuria, but later developed an increase in proteinuria and AKI (Cr 0.9 → 1.99 mg/dL). Repeat biopsy confirmed persistent C3GN without LN.
Iptacopan was just FDA approved for C3GN and was started in May 2025. Her Cr improved, but proteinuria remained largely unchanged, (UPCR 8 g/g, Cr 1.18). She was transitioned to pegcetacoplan in December 2025. Despite therapy, Cr rose to 2.58 mg/dL and proteinuria remained 6–10 g/g. The 3rd biopsy in February 2026 showed persistent C3 deposition, however new findings included severe podocytopathy with collapsing features, and 80% IFTA. C3 nephritic factor and genetic testing for C3GN and APOL1 were negative and only a CUBN mutation associated with tubular proteinuria was found. Extensive autoantibody testing for C3GN is pending.
Tacrolimus and pulse steroids (followed by taper) were initiated for presumed lupus podocytopathy, and complement inhibition was continued given persistent C3 staining. Within one month, edema resolved, kidney function and proteinuria improved (Cr 1.11 mg/dL, 2 g/g).

Discussion

Repeat biopsies are essential in SLE with C3GN to detect possible transition to LN, given that complement inhibitors are not standard therapy for LN. Notably, proteinuria progression was driven by podocytopathy, an entity not classically associated with C3GN—which is primarily a complement-mediated disease. To our knowledge, there is nothing in the literature reporting an association between C3GN and lupus podocytopathy. Treatment directed at the podocytopathy with steroids and calcineurin inhibitors led to clinical improvement.