Tubular Physiology in Acute Kidney Injury: Cell Signalling, Injury and Inflammation

Abstract

Introduction: Acute kidney injury (AKI) is a highly prevalent and devastating clinical problem, one for which new treatments and prophylactic therapies are urgently required. In order to understand and devise novel interventions, a complete under- standing of the changes seen in renal physiology in response to acute insults is required. This chapter will discuss the alterations seen in cell polarity, the cell–cell signalling in the tubular compartment and the function of the enzyme heme oxygenase-1 (HO-1) in experimental AKI. Furthermore, the role of acute inflammation in AKI will be considered, including the roles played by cytokine release, inflammatory leuko- cytes, toll-like receptors (TLRs) and complement activation on disease initiation and progression (Fig. 5.1). Much of our understanding of this area is based on experimental models of acute kidney injury in rodents such as cisplatin nephrotoxicity and renal ischaemia/reperfusion injury. While these models provide valuable information of putative pathophysiological changes within the injured kidney, it must be borne in mind that in the clinical setting, patients with AKI are usually advanced in age, with multiple comorbidities and renal insults, and where human data exists, this will also be discussed.