Heparanase in Acute Kidney Injury

Recent years have brought about fledgling realization of the role played by heparanase in the pathogenesis of diverse diseases including kidney diseases and, specifically, acute kidney injury. Human heparanase-1 is critically and uniquely engaged in cleavage of heparan sulfate, an integral part of glycocalyx and extracellular matrix where it harbors distinct growth factors, cytokines, and other biologically active molecules. The enzyme is induced and activated in acute kidney injury regardless of its causes, ischemic, nephrotoxic, septic or transplantation-related. This event unleashes a host of sequelae characteristic of the pathogenesis of acute kidney injury, such as induction and reinforcement of innate immune responses, predisposition to thrombosis, activation of monocytes/macrophages and remodeling of the extracellular matrix, thus setting up the stage for future fibrotic complications and development of chronic kidney disease. We briefly discuss the emerging therapeutic strategies of inhibiting heparanase, as well as the diagnostic value of detecting products of heparanase activity for prognostication and treatment.