ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO650

Attenuation of Renal Ischemic Reperfusion Injury in Rats with DUR-928, a Novel, First-in-Class Therapeutic in Development for Renal Disease

Session Information

  • Pharmacology
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1700 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Kim, Mee Jean, DURECT Corporation, Cupertino, California, United States
  • Wu, Hongwei, DURECT Corporation, Cupertino, California, United States
  • Lin, Wei Qi, DURECT Corporation, Cupertino, California, United States
Background

DUR-928 (5-cholesten-3β,25-diol 3-sulfate) is a first-in-class, endogenous sulfated oxysterol that regulates lipid metabolism, inflammatory response, and cell survival. It has been reported that this molecule protects against acute organ injury, including the kidney, and improved survival, from LPS-induced endotoxin shock and acetaminophen overdose/toxicity mouse models when administered at doses of 25-50 mg/kg by intraperitoneal (IP) injection.

Methods

In this study, the potential therapeutic effect of DUR-928 was investigated in a rodent model of acute kidney injury (AKI) induced by renal ischemia/reperfusion (I/R) injury. Renal ischemia was achieved by transient occlusion of the left kidney in adult male Lewis rats (9-11 weeks of age) for 50 minutes. At reperfusion, the right kidney was removed. Rats were randomized into three treatment groups (N=6 rats/vehicle control; N=11-12 rats/DUR-928) for IP administration of DUR-928 (25 mg/kg/day) or vehicle control. Three or four daily IP injections of DUR-928 or vehicle control were administered and rats were followed through 7 days of observation after I/R injury.

Results

On Days -2 (Baseline), 3 and 7 after surgery, serum creatinine (sCr) and blood urea nitrogen (BUN) were measured to evaluate renal function. Induction of I/R injury in rats was successfully achieved. sCr and BUN levels peaked significantly on Day 3 compared to Baseline. Improvement of these measures was observed on Day 7 due to spontaneous self-recovery that is characteristic of this I/R injury model. IP administration of 4 daily doses of 25 mg/kg DUR-928 resulted in significant reductions in sCr and BUN compared to vehicle-treated rats on Day 3, suggesting improved renal function. DUR-928 treatment resulted in a 63% reduction in sCr (118.4±85.9 mg/dL versus 317.3±296.6 mg/dL; p<0.05) and a 57% reduction in BUN (23.4±14.8 mg/dL versus 54.0±27.7 mg/dL; p<0.05) compared to vehicle. Similar results were found with 3 daily doses of DUR-928, with a 43% reduction in sCr (p=0.05) and 45% reduction in BUN (p<0.05), compared to vehicle.

Conclusion

The current study highlights the potential of DUR-928 to attenuate kidney injury in an acute setting and supports the continued evaluation of DUR-928 in renal disease.

Funding

  • Commercial Support