Abstract: FR-PO1247
Dual Endothelin-Angiotensin Receptor Antagonism for Transcriptional Enhanced Associate Domain (TEAD) Inhibitor-Associated Albuminuria: A Case Series
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
- Valenzuela, Diego Alfonso, The University of Chicago Medicine, Chicago, Illinois, United States
- Bonilla, Marco, The University of Chicago Medicine, Chicago, Illinois, United States
Group or Team Name
- University of Chicago Section of Nephrology
Introduction
TEAD inhibitors are promising anticancer drugs targeting the YAP/TAZ–TEAD interaction; however, proteinuria is an emerging issue. We report two patients who developed severe albuminuria on TEAD inhibitors with subsequent reduction following Dual Endothelin-Angiotensin Receptor Antagonist (DEARA) therapy.
Case Description
Patient 1, a 68-year-old female with hypertension (HTN) and mesothelioma receiving a TEAD inhibitor developed Grade A3 albuminuria (UACR 1,289-mg/g) 23 months after treatment initiation. Albuminuria worsened despite up-titration of anti-proteinuric therapy, including RASi, SGLT2, and non-steroidal MRA. DEARA use resulted in a UACR reduction of 375-mg/g in one month. The patient remained on the TEAD inhibitor without interruption.
Patient 2, a 72-year-old male with HTN and mesothelioma on the same TEAD pathway inhibitor developed Grade A3 albuminuria (UACR 1,661-mg/g) within two months of treatment start. UACR rose to 3,692-mg/g by four months; this persisted despite RASi, SGLT2, and MRA optimization. DEARA start led to a UACR of 711-mg/g within 18 days.
Discussion
TEAD inhibitor–associated albuminuria likely reflects podocyte injury, consistent with pre-clinical evidence of podocyte effacement and the established role of YAP/TAZ in glomerular filtration barrier integrity. Standard anti-proteinuric use was insufficient in both cases. Sparsentan, a DEARA blocking both ETA and ATII (AT1) receptors, achieved meaningful UACR reduction without TEAD inhibitor discontinuation. Its benefit likely reflects direct podocyte-stabilizing effects: in FSGS animal models, sparsentan attenuated ET-1–induced podocyte calcium flux, preserved podocyte number, and reduced foot process effacement beyond ARB monotherapy. ET-1 is a recognized driver of podocyte cytoskeletal injury, and its upregulation may compound the podocytopathy imposed by TEAD inhibition. Sparsentan's anti-proteinuric superiority over irbesartan in the DUPLEX trial (primary FSGS, a canonical podocytopathy) and PROTECT trial (IgAN) supports the relevance of dual ETA/AT1 blockade when conventional RAAS inhibition is insufficient. These cases suggest DEARA use may be a targeted strategy for managing TEAD inhibitor–induced podocytopathy while enabling continuation of anti-tumor therapy.