Abstract: TH-PO1164
Aprocitentan for Antivascular Endothelial Growth Factor Signaling Pathway Inhibitor-Induced Hypertension and/or Proteinuria
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
- Kala, Jaya, The University of Texas Health Science Center at Houston, Houston, Texas, United States
Background
Anti-angiogenic drugs targeting VEGF (bevacizumab) and its receptors (sunitinib, sorafenib, pazopanib, axitinib) are standard treatment for renal cell, non–small cell lung, colorectal carcinoma, and gastrointestinal stromal tumors. However, VEGF signaling pathway inhibitors (VSPIs) frequently cause hypertension and proteinuria leading to dose interruption or discontinuation. Proposed mechanisms include reduced nitric oxide and prostacyclin production, increased endothelin-1 (ET-1), microvascular rarefaction, renin–angiotensin activation, oxidative stress, and arterial stiffness. Sunitinib-induced hypertension is partially reversed by ETA/ETB antagonism with macitentan, supporting an ET-1–driven "preeclampsia-like syndrome." Current management (ACEi, ARBs, CCBs, diuretics, β-blockers) is nonspecific. These therapies are nonspecific and do not target the underlying endothelin-1 (ET-1)–driven pathophysiology. We propose the use Aprocitentan, an endothelin receptor antagonist, approved by FDA for uncontrolled hypertension, to treat hypertension and or proteinuria caused by VSPI.
Methods
We extracted data from patients who were referred to Onco-nephrology clinic for uncontrolled hypertension and or proteinuria while on VSPI agents. Among patients who were referred, 4 patients were started on Aprocicentan (while continuing their other antihypertensives). The patients are currently being closely followed for hypertension, proteinuria, cancer treatment and prognosis.
Results
Of the 4 patients who were started on treatment with Aprocicentan, two patients showed response with improved proteinuria, and all patients showed improvement in their hypertension. Due to hyperkalemia, three patients had to stop their ACEi. Three patients continued VSPI treatment while on Aprocicentan, except one who had TMA on kidney biopsy.
Conclusion
Our limited set data indicates feasibility of using Aprocitentan, to specifically target the underlying ET-1 pathophysiology of VSPI-induced hypertension and proteinuria. Use of Aprocicentan allows for continuation of VSPI cancer treatment while taking care of hypertension and proteinuria.
Table: Details of treatment, follow up blood pressure and protein, ability to continue VSPI