Novel Therapeutic Targets for Prevention and Therapy of Sepsis Associated Acute Kidney Injury

Christian   H.   Pelte; Lakhmir   S.   Chawla

Abstract

Sepsis associated Acute Kidney Injury (SA-AKI) is the leading cause of AKI in the hospital setting and its incidence is increasing. Although the exact pathophysiology and phenotype of SA-AKI are not known, it is widely accepted that SA-AKI has a multi-injury pathway. This form of AKI has components of ischemia-reperfusion injury, direct inflammatory injury, coagulation and endothelial cell dysfunction, and apoptosis. As such, multiple agents have been shown in pre-clinical studies to ameliorate SA-AKI, but there are no interventions currently available for the treatment of SA-AKI. Promising agents that are in development include toll-like receptor inhibition, IL-10 augmentation, modulators of the protein C pathway, and mesenchymal stem cell mediated therapeutics. The aim of this review is to review the pathophysiology of SA-AKI and the therapeutic interventions that are under development to treat this complex and morbid disease.

Keywords: Sepsis associated acute kidney injury, inflammation, IL-6, toll-like receptors, IL-10, ischemia reperfusion injury, apoptosis, activated protein C, soluble thrombomodulin, ethyl pyruvate