University of Pittsburgh researchers have discovered that the timing of administration of a potential treatment, UPHD186, can be crucial to recovery in patients with sepsis-associated acute kidney injury (S-AKI). This discovery could dramatically change clinical approaches to treating S-AKI by increasing the chances of survival and reducing risks of long-term and irreversible renal damage for patients.
Description
S-AKI is a common life-threatening complication in critically ill patients, increasing mortality six to eightfold. In surviving patients, S-AKI increases the risk of developing chronic kidney disease (CKD) threefold. Up to one quarter of surviving patients will require lifelong treatment, including dialysis or transplantation. Many patients with sepsis will develop S-AKI before presenting to the hospital—meaning that appropriate treatment is key. There is a clinical need to develop effective treatments to treat S-AKI to not only save the lives of critically ill patients, but also prevent the development of CKD and the associated lifelong complications. This novel treatment approach would ensure that treatment is delivered at an optimal time post-onset of S-AKI to prevent impairment of renal immune systems vital for renal recovery.
Applications
- Sepsis-induced acute kidney injury
- Nephrotoxicity
- Ischemia-reperfusion injury
Advantages
Of patients admitted to hospital with septic shock, 50% will have clinical evidence of S-AKI with a further 20% presenting with biomarker evidence of S-AKI. Research has found that 4-(phenylthio)butanoic acid (PTBA), a histone deacetylase inhibitor, can promote the proliferation of embryonic kidney progenitor cells, potentially providing a novel treatment approach for S-AKI. A PTBA prodrug, UPHD186 has been developed and animal studies have confirmed efficacy. Early administration of PTBA prodrugs could be harmful if renal injury is still ongoing and this novel treatment strategy involves optimal timing of treatment with UPHD186. Positive outcomes can include improvement in sepsis survival, lessening of renal tubular injury, and prevention of CKD.
Invention Readiness
Using animal models of S-AKI that led to renal fibrosis (which is indicative of a transition to CKD), the impacts of early (48 h) or delayed (96 h) treatment with a 7-day course of UPHD186 have been investigated. Delayed treatment, (when inflammation has subsided) was shown to be effective in promoting recovery from S-AKI and in preventing the development of fibrosis. The results suggest that early treatment, while renal inflammation is still ongoing, could interfere with the patient’s recovery. It is now vital to understand the optimal time frame for UPHD186 delivery and potentially develop biomarkers to aid clinicians in making treatment decisions that improve patient outcomes.
IP Status
https://patents.google.com/patent/WO2020240524A2
