Abstract: TH-PO1162
Complement-Mediated Renal Thrombotic Microangiopathy Associated with Anti-Vascular Endothelial Growth Factor and Immune Checkpoint Inhibitor Therapy Successfully Treated with Eculizumab
Session Information
- Onconephrology: Emerging Biomarkers, Preclinical Models, Clinical Challenges, and Therapeutic Strategies
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1600 Onconephrology
Author
- Fan, Qiuling, Shanghai General Hospital, Shanghai, China
Introduction
Renal thrombotic microangiopathy (TMA) is an increasingly recognized complication of anti-cancer therapies, particularly anti-vascular endothelial growth factor (VEGF) agents and immune checkpoint inhibitors (ICIs). Although endothelial injury is considered the primary mechanism, recent evidence suggests that complement activation may contribute to disease progression in selected patients.
Case Description
A 72-year-old man with renal cell carcinoma and prostate adenocarcinoma presented with progressive kidney dysfunction, nephrotic-range proteinuria, and anemia during treatment with lenvatinib followed by PD-1 inhibitor therapy. Baseline serum creatinine had been stable at 70–80 μmol/L but progressively increased to 234 μmol/L over 7 months. Laboratory evaluation revealed nephrotic-range proteinuria (24-hour urinary protein 11.16 g), hypoalbuminemia (22.1 g/L), elevated lactate dehydrogenase, reticulocytosis, schistocytes, and anemia (hemoglobin 85 g/L), consistent with microangiopathic hemolytic anemia.Complement testing demonstrated elevated soluble C5b-9 and CH50 levels. Kidney biopsy showed subacute TMA characterized by endothelial swelling, capillary wall thickening, luminal narrowing, thrombus formation, focal segmental glomerulosclerosis-like lesions, and chronic active tubulointerstitial nephritis with C3 deposition. Genetic testing for complement-related variants was negative.Despite discontinuation of anti-cancer agents and corticosteroid therapy, renal function continued to deteriorate. Given evidence of complement activation, eculizumab therapy was initiated. Following treatment, serum creatinine decreased by approximately 21%, proteinuria decreased by 85%, and hemoglobin improved by 16%, with stabilization of hematologic parameters.
Discussion
This case highlights complement activation as a potential pathogenic mechanism in cancer therapy-associated renal TMA, even in the absence of identifiable complement gene mutations. The favorable clinical response to eculizumab suggests that complement inhibition may represent an effective therapeutic strategy in selected patients with anti-VEGF- and ICI-associated TMA.
Early recognition of complement-mediated TMA and prompt initiation of targeted therapy may improve renal and hematologic outcomes.