Abstract: SA-PO0701
Beyond Acute Interstitial Nephritis: C3 Glomerulopathy as a Rare and Underrecognized Face of Immunotherapy Nephrotoxicity
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
- Siddiqi, Mahwash, Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, United States
- Raza, Muhammad, Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, United States
- Tahir, Maria, Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, United States
- Trivedi, Naman, Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, United States
- Abendroth, Catherine, Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, United States
- Farooq, Umar, Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, United States
- Miller, Ronald P., Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, United States
- Verma, Navin, Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, United States
- Ghahramani, Nasrollah, Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, United States
- Portela-Colon, Rafael, Penn State Health Milton S Hershey Medical Center, Hershey, Pennsylvania, United States
Group or Team Name
- Division of Nephrology
Introduction
Immune checkpoint inhibitors (ICIs) can cause immune-mediated nephrotoxicity, most commonly acute interstitial nephritis (AIN). ICI-induced C3 glomerulopathy (C3GN) is rare. We report biopsy-proven C3GN with concurrent AIN in non-small cell lung cancer (NSCLC) treated with pembrolizumab, with renal response after rituximab.
Case Description
A 73-year-old man with CKD stage 3b/4, baseline creatinine 2.9–3.1 mg/dL, metastatic NSCLC adenocarcinoma treated with carboplatin, pemetrexed, pembrolizumab, and radiation, prostate cancer, and Takotsubo cardiomyopathy presented with severe AKI on CKD several weeks after ICI exposure. Peak creatinine was 6.63 mg/dL with refractory hyperkalemia requiring hemodialysis. Interval imaging showed tumor regression, favoring ICI injury over paraneoplastic glomerulonephritis.
Renal biopsy showed mesangial non-amyloid PAS-positive, Congo Red-negative expansion, tubular injury, moderate interstitial fibrosis/tubular atrophy, CD3-predominant interstitial inflammation, and peritubular capillaritis. Immunofluorescence showed granular capillary wall IgM 3+ and C3 2+, with negative IgG, IgA, C1q, kappa, and lambda. Limited electron microscopy showed subendothelial deposits without fibrillar or tubular deposits. Findings supported C3GN-like complement-mediated injury with concomitant AIN. Pembrolizumab was discontinued. As the patient declined ongoing steroids, mycophenolate was avoided; rituximab was selected. After rituximab 1 g twice, 2 weeks apart, UPCR improved from 2.0 and 1.79 g/g pre-treatment to 0.9 g/g 1 month later. At follow-up, he was clinically well and back to part-time work.
Discussion
ICI-induced C3GN is a rare, distinct entity driven by immune dysregulation from checkpoint blockade rather than an intrinsic complement pathway defect. Prompt ICI discontinuation is critical for renal recovery. Case series suggest favorable responses with a reduction in proteinuria following Rituximab. Unlike primary C3GN, which is commonly treated with steroids and mycophenolate due to persistent complement dysregulation, ICI-induced C3GN may differ mechanistically. Complement blockade may warrant further study in steroid or rituximab-refractory cases, where ongoing complement activation may contribute to persistent inflammation