Blocking the immune response in ischemic acute kidney injury: the role of adenosine 2A agonists

Abstract

Acute kidney injury (AKI) is associated with a high degree of morbidity and mortality and its incidence is increasing. These factors, together with a lack of successful clinical trials, necessitate a comprehensive evaluation of the pathogenesis of AKI and trial design. The progress that has been made in elucidating the pathogenesis of AKI has defined inflammation as an early event and therefore a potential target for therapeutic intervention. This Review summarizes recent advances in our understanding of the role of inflammation in AKI as well as our approach to limiting inflammation using compounds that stimulate adenosine 2A receptors (A(2A)Rs). A(2A)Rs are members of a family of guanine nucleotide-binding proteins that have become a focus of interest primarily because of their ability to broadly inactivate the inflammatory cascade. An A(2A) agonist-ATL146 ester (ATL146e)-is currently being tested in a phase III clinical trial as a pharmacological stress agent in cardiac perfusion imaging studies. This study, together with extensively published preclinical data, will facilitate testing of ATL146e in human trials of AKI.