Abstract: FR-PO1283
Immune Complex-Mediated Membranoproliferative Glomerulonephritis Complicating Dual Immune Checkpoint and Vascular Endothelial Growth Factor Inhibitor Therapy in Hepatocellular Carcinoma
Session Information
- Onconephrology: Diagnostic Dilemmas, Therapy-Related Toxicities, and Clinical Cases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1600 Onconephrology
Authors
- Brahmandam, Gayatri, Adichunchanagiri Institute of Medical Sciences, Mandya, KA, India
- Tchakarov, Amanda, The University of Texas Health Science Center at Houston, Houston, Texas, United States
- Kodali, Sudha, Houston Methodist Hospital, Houston, Texas, United States
- Kaseb, Ahmed Omar, The University of Texas MD Anderson Cancer Center Division of Cancer Medicine, Houston, Texas, United States
- Lin, Jamie S., The University of Texas MD Anderson Cancer Center Division of Internal Medicine, Houston, Texas, United States
Introduction
Membranoproliferative glomerulonephritis (MPGN) is associated with infections, malignancies, autoimmune diseases, and drugs. In patients with hepatocellular carcinoma (HCC), immune checkpoint inhibitors (ICI) and vascular endothelial growth factor (VEGF) inhibitors can independently cause glomerulopathy through distinct mechanisms complicating etiology and management.
Case Description
A 60-year-old African American male with hepatitis C virus-related cirrhosis and multifocal HCC developed nephrotic-range proteinuria during systemic cancer therapy while undergoing liver transplant evaluation. Following sustained virologic response, he was initiated on atezolizumab (PD-L1) and bevacizumab (anti-VEGF). After 16 cycles of bevacizumab and 21 doses of atezolizumab, he developed worsening kidney function (sCr 1.08 to 1.41 mg/dl), nephrotic-range proteinuria (24 h urine protein 7.1 g), and hematuria prompting discontinuation. Serologies showed ANA 1:160, negative dsDNA, ANCA, and cryoglobulins, normal C3, and elevated C4 (52 mg/dl). Kidney biopsy revealed immune complex-mediated MPGN with polytypic immunoglobulin deposition and hyaline thrombi. After multidisciplinary review of his malignancy and transplant candidacy, prednisone was initiated and tapered over 3 months with partial renal recovery (sCr 1.15 mg/dl, UPCR 3.15 g/g). Subsequent treatment with lenvatinib resulted in markedly worsened proteinuria and was stopped. Initiation of sorafenib was well-tolerated with continued proteinuria improvement (UPCR 1.59 g/g). The patient successfully underwent liver transplantation with stable post-transplant renal function (sCr 1.14 mg/dl, UPCR 0.99 g/g).
Discussion
Immune complex-MPGN with endothelial injury, positive ANA, and temporal relationship to ICI and anti-VEGF therapy supported a multifactorial pathogenesis in which atezolizumab drove the immune dysregulation and bevacizumab amplified endothelial vulnerability. In the absence of cryoglobulinemia, B cell-directed therapy was deferred in favor of corticosteroids alone, achieving partial remission while preserving transplant candidacy. The differential renal response to VEGF-directed agents and sustained post-transplant recovery underscore the importance of mechanistically informed management when immune-mediated kidney injury occurs amid competing oncologic and transplant considerations.