Kidney Week

Abstract: FR-PO0515

sST2-Treg Axis in Cardiac Surgery-Associated AKI (CSA-AKI)

Session Information

• CKM: Clinical - Trials, Epidemiology, and Biomarkers
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Cardiovascular-Kidney-Metabolic Health

• 602 Cardiovascular-Kidney-Metabolic Health: Clinical

Authors

• Sabapathy, Vikram, University of Virginia, Charlottesville, Virginia, United States

Vikram Sabapathy, PhD

• Dogan, Murat, University of Tennessee-Health Science Center College of Medicine, Memphis, Tennessee, United States

Murat Dogan, MD, PhD

• Pelletier, Oliver B., University of Virginia, Charlottesville, Virginia, United States

Oliver B. Pelletier, PhD

• Ma, Jennie Z., University of Virginia, Charlottesville, Virginia, United States

Jennie Z. Ma

• Okusa, Mark D., University of Virginia, Charlottesville, Virginia, United States

Mark D. Okusa, MD, FASN

• Rosner, Mitchell H., University of Virginia, Charlottesville, Virginia, United States

Mitchell H. Rosner, MD, FASN

• Sharma, Rahul, University of Virginia, Charlottesville, Virginia, United States

Rahul Sharma, MS, PhD

Background

Cardiac Surgery-Associated AKI (CSA-AKI) is a common serious complication following cardiac surgery, driven by ischemia–reperfusion injury, inflammation, and oxidative stress. Interleukin-1 receptor-like 1 (IL1RL1 or ST2), a member of the IL-1 receptor family, exists as both a membrane-bound receptor (ST2) and a soluble decoy receptor (sST2). ST2 ligand IL-33 plays a critical role in immune regulation and tissue repair. Elevated circulating sST2 levels are a recognized marker for mortality in cardiac failure. ST2-expressing Regulatory T cells (Tregs) are potent suppressors of inflammation and promote tissue repair. We investigated the relationship between circulating sST2 levels and Treg dynamics in patients undergoing cardiac surgery to evaluate their potential as predictive biomarkers for post-surgery AKI.

Methods

Plasma and peripheral blood mononuclear cells (PBMCs) were collected from 214 patients undergoing cardiac surgery before and 24 hours post-surgery. Plasma sST2 level was measured using quantitative sandwich ELISA. Frequency of CD4⁺ ST2⁺Foxp3⁺CD127lo Tregs was quantified by flow cytometry, and incidence of AKI post-surgery was determined using KDIGO criteria. Comparisons were performed between pre- and post-surgery, as well as between AKI versus non-AKI groups.

Results

Patients who developed AKI after cardiac surgery had significantly fewer circulating ST2⁺ Tregs before undergoing surgery (p=0.034) compared to those who did not develop AKI. Plasma sST2 levels increased significantly following cardiac surgery (p<0.001) in all patients. Patients who developed AKI exhibited markedly higher post-surgery sST2 levels compared with the non-AKI patients (p<0.001). While circulating levels of total Tregs were lower in patients who developed AKI post-cardiac surgery (p=0.02), Treg abundance also demonstrated a substantial decrease from pre-surgery to post-surgery timepoints (p=0.03), suggesting impaired immunoregulatory responses associated with renal injury susceptibility.

Conclusion

Lower pre-surgery ST2⁺ Treg levels are predictive of CSA-AKI. The inverse relationship between elevated circulating sST2 and reduced Treg levels is associated with an increased risk of AKI following cardiac surgery. The data implicates dysregulation of the IL-33/ST2 Treg axis as a potential mechanistic contributor to CSA-AKI. Combined sST2 and Treg profiling may offer improved prognostic value for perioperative CSA-AKI risk stratification.

Funding

• NIDDK Support