Alkaline phosphatase
Alkaline phosphatase has been investigated as a treatment for AKI. While the mechanism of action remains incompletely understood, the underlying principle is dephosphorylation of endotoxins and attenuation of the inflammatory response. A prospective, randomized, double-blind, placebo-controlled trial in 2012 demonstrated a clear improvement in endogenous creatinine clearance (P=0.02) along with reduced requirement and duration of RRT after 28 days.41 The same study also measured urinary biomarkers and demonstrated significant decreases in kidney injury molecule-1 and IL-18, both described to have prognostic utility for RRT requirement. This followed from earlier studies which demonstrated the administration of alkaline phosphatase was associated with reduced expression of inducible nitric oxide synthase in the proximal tubule. Most recently, another Phase I trial to assess the pharmacokinetic profile and safety of recombinant alkaline phosphatase demonstrated an acceptable profile, thus enabling progress to further interventional studies in SA-AKI.42 This is currently recruiting.