Abstract: FR-PO0687
Collapsing FSGS Progression to ESRD After Combination Therapy with Pembrolizumab and Enfortumab Vedotin: A Case Report
Session Information
- Glomerular Diseases: Membranous Nephropathy, FSGS, and Podocytopathies
October 23, 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
- Hitti, George, University of California Irvine School of Medicine, Irvine, California, United States
- Gee, Caroline A., University of California Irvine School of Medicine, Irvine, California, United States
- Hanna, Ramy Magdy, University of California Irvine School of Medicine, Irvine, California, United States
Introduction
Pembrolizumab (PB), a PD-1 immune checkpoint inhibitor, and enfortumab vedotin (EV), a Nectin-4 targeting antibody-drug conjugate delivering the microtubule-disrupting payload MMAE, represent the current standard of care for advanced urothelial carcinoma. While PB-associated glomerulopathy is a recognized rare complication, rapid one-month progression to end-stage renal disease (ESRD) following the EV-PB combination has not been previously described.
Case Description
A 76-year-old male with high-grade urothelial carcinoma and baseline Stage 4 CKD (eGFR 25 mL/min/1.73 m^2, creatinine 2.5 mg/dL) secondary to prior cisplatin exposure was initiated on PB 200 mg IV and EV 1 mg/kg IV on a 21-day cycle. Within one month, he developed AKI presenting with a creatinine of 3.1 mg/dL, eGFR of 20 mL/min/1.73 m^2, and nephrotic-range proteinuria of 13.1 g[GC1] /24 hours. Renal biopsy confirmed cFSGS with 53% global glomerulosclerosis and 70% cortical fibrosis. Both agents were discontinued and rituximab was initiated; however, renal function still deteriorated. Six months later he presented with labs of: creatinine 8.4 mg/dL, eGFR 6 mL/min/1.73 m^2; requiring emergent hemodialysis. Renal function did not recover, and the patient progressed to permanent ESRD.
Discussion
This case highlights three key teaching points. First, pre-existing CKD from prior nephrotoxic chemotherapy amplifies the risk of irreversible cFSGS progression following ADC-immunotherapy, underscoring the need for baseline nephrology evaluation in this population. Second, we propose a novel synergistic mechanism whereby PB-induced podocyte dedifferentiation and cell-cycle re-entry renders those podocytes selectively vulnerable to MMAE-mediated cytotoxicity which can potentially explain the unusually rapid deterioration observed. Third, once advanced interstitial fibrosis is established, immunosuppressive salvage is unlikely to alter the trajectory, and its toxicity must be weighed against a negligible probability of benefit. Notably, PB-induced cFSGS typically remits within 2–3 months of drug discontinuation; however, the literature on dual therapy with EV remains limited.