title: Recent early clinical drug development for acute kidney injury.
abstract: Despite significant need and historical trials, there are no effective drugs in use for the prevention or treatment of acute kidney injury (AKI). There are several promising agents in early clinical development for AKI and two trials have recently been terminated. There are also exciting new findings in pre-clinical AKI research. There is a need to take stock of current progress in the field to guide future drug development for AKI. Areas covered: The main clinical trial registries, PubMed and pharmaceutical company website searches were used to extract the most recent clinical trials for sterile, transplant and sepsis-associated AKI. We summarise the development of the agents recently in clinical trial, update on their trial progress, consider reasons for failed efficacy of two agents, and discuss new paradigms in pre-clinical targets for AKI. Agents covered include- QPI-1002, THR-184, BB-3, heme arginate, human recombinant alkaline phosphatase (recAP), ciclosporin A, AB103, levosimendan, AC607 and ABT-719. Expert opinion: Due to the heterogenous nature of AKI, agents with the widest pleiotropic effects on multiple pathophysiological pathways are likely to be most effective. Linking preclinical models to clinical indication and improving AKI definition and diagnosis are key areas for improvement in future clinical trials.
authors.affiliation: a MRC Centre for Inflammation Research, Royal Infirmary of Edinburgh , University of Edinburgh , Edinburgh , UK.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Gallagher
authors.affiliation: a MRC Centre for Inflammation Research, Royal Infirmary of Edinburgh , University of Edinburgh , Edinburgh , UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: O'neill
authors.affiliation: a MRC Centre for Inflammation Research, Royal Infirmary of Edinburgh , University of Edinburgh , Edinburgh , UK.
authors.forename: Ewen M
authors.initials: EM
authors.lastname: Harrison
authors.affiliation: b MRC Centre for Regenerative Medicine, Royal Infirmary of Edinburgh , University of Edinburgh , Edinburgh , UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Ross
authors.affiliation: a MRC Centre for Inflammation Research, Royal Infirmary of Edinburgh , University of Edinburgh , Edinburgh , UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wigmore
authors.affiliation: a MRC Centre for Inflammation Research, Royal Infirmary of Edinburgh , University of Edinburgh , Edinburgh , UK.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hughes
mesh_terms: D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000818:Animals; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D015507:Drugs, Investigational / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D058990:Molecular Targeted Therapy; D018805:Sepsis / Q000150:complications
chemical_list: D015507:Drugs, Investigational
keywords: Acute kidney injury; alkaline phosphatase; bone morphogenetic protein receptor; cardiac surgery AKI; delayed graft function; hepatocyte growth factor; p53; sepsis associated AKI; α-melanocortin receptor 1