Abstract: FR-PO1263
A Case of Cabozantinib-Associated Thrombotic Microangiopathy with Favorable Response to Complement Inhibition
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
- Torres, Edwin Xavier, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Kovvuru, Karthik, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Kanduri, Swetha Rani, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
Introduction
Tyrosine kinase inhibitor (TKI) associated thrombotic microangiopathy (TMA) is an increasingly recognized complication of targeted cancer therapy. Diagnosis of renal limited TMA may be challenging in patients with diabetic nephropathy, where chronic glomerular changes can obscure superimposed endothelial injury. We report a case of cabozantinib associated renal limited TMA superimposed on diabetic nephropathy with favorable response to complement inhibition.
Case Description
A 56-year-old man with metastatic renal cell carcinoma was referred for worsening kidney function, uncontrolled hypertension, bilateral lower extremity edema. He was started on Cabozantinib, a TKI one year ago for his metastatic renal cell carcinoma. Other medical history included diabetes mellitus (HbA1c 6.8%) and hypertension. Laboratory evaluation showed serum creatinine (Scr) of 4 mg/dl (baseline 1.5-1.6mg/dL), serum albumin 1.9 g/dL and lactate dehydrogenase 624 U/L. ADAMTS13, Shiga toxin, ANA, anti-dsDNA, MPO, PR3, anti-GBM, and PLA2R testing were negative. Urinalysis showed 4+ proteinuria and 2+ hematuria without pyuria, urine protein creatinine ratio was 14.5 g/g. Despite discontinuation of cabozantinib for 2 months, renal function continued to decline. Kidney biopsy was performed which demonstrated nodular diabetic glomerulosclerosis with mesangial expansion and segmental glomerulosclerosis. Additional findings included glomerular basement membrane double contours, subendothelial lucency, mesangiolysis and extensive foot process effacement, consistent with superimposed TMA. Due to persistent renal dysfunction and ongoing endothelial injury, ravalizumab was initiated. Six weeks later, Scr improved from 4.0 to 2.4 mg/dL and proteinuria decreased from 14.5 to 7 g/g with marked improvement in edema.
Discussion
TKI associated renal limited TMA can be difficult to recognize in patients with underlying diabetic nephropathy. Persistent nephrotic syndrome and worsening kidney function despite withdrawal of the offending agent should raise concern for ongoing complement mediated endothelial injury. This case highlights the importance of recognizing superimposed TMA in diabetic kidney disease and suggests a potential role for complement inhibition.