Kidney Week

Abstract: TH-PO0526

Use of Endothelin Receptor Blockade in Patients with IgAN and Advanced CKD: A Case Series

Session Information

• Glomerular Diseases: IgAN, IgA Vasculitis, and More
  October 22, 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

• Alhaddad, Juliano, Cleveland Clinic, Cleveland, Ohio, United States

Juliano Alhaddad, MD

• Dhingra, Jagmeet S., Cleveland Clinic, Cleveland, Ohio, United States

Jagmeet S. Dhingra, MD, FASN

• Ferreira Provenzano, Laura, Cleveland Clinic, Cleveland, Ohio, United States

Laura Ferreira Provenzano, MD

• Cavanaugh, Corey J., Cleveland Clinic, Cleveland, Ohio, United States

Corey J. Cavanaugh, DO

Introduction

IgA Nephropathy (IgAN) has undergone a treatment revolution. Sparsentan, a dual endothelin receptor and angiotensin receptor blocker (DEARA), and Atrasentan, a highly selective endothelin A antagonist (ERA), have been shown to reduce proteinuria and eGFR decline in patients with IgAN and an eGFR ≥30 mL/min/1.73 m2. The utility of these drugs in advanced kidney disease is largely unexplored. Here, we present the case of 5 patients with eGFR < 30 mL/min/1.73 m2 who were treated with a DEARA or ERA.

Case Description

Patient characteristics are summarized in table 1. Patient 4 had the lowest eGFR of 22 mL/min/1.73 m2. The four patients who received DEARA had at least a 50% reduction in their proteinuria. Patient 3, treated with ERA, had 30% reduction in his proteinuria level after only one month of therapy. Adverse events included hyperkalemia (Patients 1, 2, and 5) and worsening kidney function (Patients 2 and 5), which were managed with dose reduction (Patient 2). DEARA was held only in patient 5, who had progressive worsening of kidney function over two years from IgAN progression and ischemic ATN from GLP-1/GIP agonists.

Discussion

Sparsentan and Atrasentan have received FDA approval for IgAN following the phase III PROTECT and ALIGN trials, which showed significant reductions in proteinuria in patients with an eGFR ≥30 mL/min/1.73 m2. Data on the safety and efficacy of these agents in patients with more advanced chronic kidney disease (i.e., eGFR <30 mL/min/1.32 m2) are sparse, limiting exposure to these agents in this group. The cases presented here show promising signs that these agents are effective in reducing proteinuria, even at lower eGFR, with 4 patients achieving at least partial remission and one patient achieving complete remission. These agents may be relatively safe when monitored closely for kidney function and hyperkalemia. Furthermore, a reduced-dose regimen might be sufficient to mitigate these side effects, as in patient 2. Large randomized controlled trials are needed to validate these observations.