Abstract: SA-PO0269
Proteomic Profiling and Targets of Treprostinil Therapy to Reduce Renal Ischemia-Reperfusion Injury
Session Information
- AKI: Mechanisms - Cell Signaling
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Oladepo, Mariam Olaide, University of Rhode Island, Kingston, Rhode Island, United States
- Ding, Meiwen, University of Rhode Island, Kingston, Rhode Island, United States
- Tolbert, Evelyn, Brown University Health, Providence, Rhode Island, United States
- Birkenbach, Mark, Brown University Health, Providence, Rhode Island, United States
- Gohh, Reginald, Brown University Health, Providence, Rhode Island, United States
- Ghonem, Nisanne S., University of Rhode Island, Kingston, Rhode Island, United States
Background
Renal ischemia-reperfusion injury (IRI) is a significant contributor to acute kidney injury and delayed graft function during kidney transplantation, with no treatment available. We previously demonstrated the efficacy of treprostinil (Remodulin®), an FDA-approved prostacyclin analog, in reducing renal IRI in vivo. This study investigates novel biomarkers, pathways and reno-protective mechanisms of treprostinil during renal IRI in vivo.
Methods
Male Sprague Dawley rats were randomly divided into sham, placebo, and treprostinil-treated groups, and subjected to bilateral renal IRI (45 mins) followed by reperfusion (1-48 hrs). Treprostinil was administered subcutaneously at 18-24 hrs before renal IRI (n = 5-8 / group). Serum and kidney tissue were collected for biochemical, histological and proteomic analyses at 6, 24 and 48 hrs post reperfusion..
Results
Treprostinil reduced peak serum creatinine levels by 52% vs. placebo (P<0.05), and histology showed a reduction of necrotic tubules in the outer medulla and cortex of the kidney by 50% vs. placebo (P<0.01) at 24 hours post-reperfusion.
Proteomic profiling in renal tissues detected more than 2900 proteins, including 91, 58 and 60 differentially expressed proteins (DEPs) at 6, 24, and 48 hrs post-reperfusion, respectively between animal groups (p<0.05). Similarly, in serum more than 800 proteins were detected, including 197 and 106 DEPs at 24 and 48 hrs post-reperfusion, respectively between animal groups (p<0.05). Pathway analysis using STRING and GO, showed a correlation between DEPs, including pathways that regulate molecular functions, e.g., oxygen, heme, protease and complement binding; biological processes, e.g., acute phase response, stress, involving cellular components of the extracellular space, cytoplasm, and apical components of the cell.
Conclusion
In conclusion, IRI and treprostinil therapy alter renal and serum protein expressions as early as 6 hrs and up to 48 hrs post-reperfusion. These findings identify specific proteins regulated during renal IRI and provide mechanistic insight of novel biomarkers and therapeutic targets of treprostinil during renal IRI.
Funding
- Other NIH Support – United Therapeutics