Kidney Week

Abstract: FR-PO0731

Lenvatinib-Associated FSGS Beyond Thrombotic Microangiopathy

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

• Mira, Michael, Robert Wood Johnson University Hospital, New Brunswick, New Jersey, United States

Michael Mira, MD

• Appelbaum, Zachary, Robert Wood Johnson University Hospital, New Brunswick, New Jersey, United States

Zachary Appelbaum, MD, JD

• Hashmi, Nooruddin, Robert Wood Johnson University Hospital, New Brunswick, New Jersey, United States

Nooruddin Hashmi, MD

• Fyfe-Kirschner, Billie S., Robert Wood Johnson University Hospital, New Brunswick, New Jersey, United States

Billie S. Fyfe-Kirschner, MD

Introduction

Vascular endothelial growth factor (VEGF) signaling plays an integral role in maintaining the structure and function of the glomerular endothelium and the podocytes. Inhibition of VEGF can result in nephrotoxicity in some patients. The most common manifestations of renal toxicity include hypertension and proteinuria, but thrombotic microangiopathy (TMA) and podocytopathies are less frequently observed. Lenvatinib, a tyrosine kinase inhibitor targeting the VEGF receptor, is utilized in the treatment of various malignancies, including hepatocellular carcinoma and thyroid cancer. We report a case of lenvatinib associated nephrotic range proteinuria with a kidney biopsy notable for endothelial injury and focal segmental glomerulosclerosis.

Case Description

A 78 year old woman with papillary thyroid carcinoma was initially treated with thyroidectomy followed by radioactive iodine therapy. Despite radiologic evidence of residual tumor with laryngeal invasion, the patient declined surgical intervention and was initiated on lenvantinib for locally invasive disease. One month after starting anti VEGF therapy, a urinalysis revealed 3+ protein with a urine to protein ratio of 3.8 g/g. A comprehensive serologic workup - including infectious, paraprotein, and autoimmune studies - was unremarkable. Kidney biopsy demonstrated segmental glomerulosclerosis with tip lesions and endothelial swelling. Electron microscopy revealed subendothelial lucency and 20–30% foot process effacement, consistent with VEGF inhibitor associated endothelial and with secondary podocytopathy. Immunofluorescence studies were negative. The lenvatinib was discontinued and RAAS inhibition was optimized, resulting in improvement in proteinuria.

Discussion

VEGF inhibition disrupts the integrity of both the glomerular endothelium and the podocyte, leading to endothelial injury and podocytopathies, including FSGS. The coexistence of these findings suggests a shared anti VEGF mediated mechanism of injury. The negative serologic workup and the absence of immune complex deposition argue against alternative causes of proteinuria. The observed improvement in the degree of proteinuria after drug discontinuation and initiation of RAAS blockade supports a causal relationship between the lenvatinib and the patient’s renal manifestations. This case highlights the importance of blood pressure and proteinuria monitoring on patients receiving anti VEGF therapy.