Alkaline phosphatase treatment of acute kidney injury—an update

Through improved insights into the increasing incidence and detrimental effects of acute kidney injury (AKI), its clinical relevance has become more and more apparent. Although treatment strategies for AKI have also somewhat improved, an adequate remedy still does not exist. Finding one is complicated by a multifactorial pathophysiology and by heterogeneity in the patient population. Alkaline phosphatase (ALP) has been suggested as a therapy for sepsis-associated AKI because of its protective effects against lipopolysaccharide (LPS)-induced inflammation and kidney injury in animals. However, its effectiveness as an AKI treatment has not been demonstrated definitively. Because the anti-inflammatory properties of ALP are likely not reliant on a direct effect on LPS itself, we postulate that other pathways are much more important in explaining the renoprotective properties ascribed to ALP. The re-evaluation of which properties of the ALP enzyme are responsible for the benefit seen in the lab is an important step in determining where the true potential of ALP as a treatment strategy for AKI in the clinic lies. In this review we will discuss how ALP can prevent activation of harmful pro-inflammatory receptors, redirect cell–cell signalling and protect barrier tissues, which together form the basis for current knowledge of the role of ALP in the kidney. With this knowledge in mind and by analysing currently available clinical evidence, we propose directions for new research that can determine whether ALP as a treatment strategy for AKI has a future in the clinical field.