Acute kidney injury: emerging pharmacotherapies in current clinical trials

Abstract

Acute kidney injury (AKI) is a significant source of morbidity and mortality in pediatric patients, affecting more than one quarter of critically ill children. Despite significant need, there are no targeted therapies to reliably prevent or treat AKI. Recent advances in our understanding of renal injury and repair signaling pathways have enabled the development of several targeted pharmaceuticals. Here we review emerging pharmacotherapies for AKI that are currently in clinical trials. Categorized by their general mechanism of action, the therapies discussed include anti-inflammatory agents (recAP, AB103, ABT-719), antioxidants (iron chelators, heme arginate), vasodilators (levosimendan), apoptosis inhibitors (QPI-1002), and repair agents (THR-184, BB-3, mesenchymal stem cells).

Chemical modifications of nucleic acid drugs and their delivery systems for gene‐based therapy

“…The first siRNA drug candidate for systemic administration, QPI‐1002, can temporarily inhibit proapoptotic p53 protein expression . It was investigated for the prevention of delayed graft function (DGF) in recipients of an older donor kidney transplant.…”

“…It was investigated for the prevention of delayed graft function (DGF) in recipients of an older donor kidney transplant. Uncoated kidney‐targeted drug QPI‐1002 is accumulated in the kidneys to reduce the incidence and severity of DGF with older donor kidney transplant . Patients were recruited for phase III trial in 2015 by Quark Pharmaceuticals.…”

“…The first siRNA drug candidate for systemic administration, QPI-1002, can temporarily inhibit proapoptotic p53 protein expression. 55 It was investigated for the prevention of delayed graft function (DGF) in recipients of an older donor kidney transplant. Uncoated kidney-targeted drug QPI-1002 is accumulated in the kidneys to reduce the incidence and severity of DGF with older donor kidney transplant.…”

“…Uncoated kidney-targeted drug QPI-1002 is accumulated in the kidneys to reduce the incidence and severity of DGF with older donor kidney transplant. 55,56 Patients were recruited for phase III trial in 2015 by Quark Pharmaceuticals.…”

Acute kidney injury and continuous renal replacement therapy in children; what pediatricians need to know

“…Through understanding the pathophysiology of AKI, potential therapeutic interventions, such as anti-inflammatory agents including recombinant alkaline phosphate [ 53 ], costimulatory molecule CD28 receptor antagonist [ 54 ], antioxidants, vasodilator-calcium sensitizer levosimendan [ 55 ], apoptosis inhibitors (p53 siRNA) and repair agents including bone morphogenetic protein-7 receptor agonist hepatocyte growth factor, and mesenchymal stem cells, are now under consideration [ 53 ].…”