Pathogenesis of acute kidney injury: effects of remote tissue damage on the kidney

Abstract

The modern definition and classification of acute kidney injury (AKI) has now been applied to thousands of patients around the world and in different settings. Epidemiology is shedding intense light on the credibility of our fundamental notions of how AKI occurs and why. It is clear from multiple studies that sepsis is the leading etiology of AKI, although other settings associated with systemic inflammation (polytrauma, burns, pancreatitis, cardiopulmonary bypass) also represent important means of exposure. Early in sepsis-induced AKI, there is an intense reduction in glomerular filtration with only mild structural changes mostly limited to the tubular epithelium. Although endothelial and interstitial changes may also occur, histopathology in sepsis-induced AKI is characteristically bland. Of course, many patients with severe AKI do not recover (as many as 50% in recent studies), and these patients ultimately develop severe structural alterations including fibrosis. Recent evidence suggests that cells in injured and infected tissues release immunological danger signals or danger-associated molecular patterns which communicate with remote organs including the kidney, where they activate dendritic cells and T cells and thus initiate inflammation. Dissonance of mediator secretion and cell responses may lead to persistent injury and de novo chronic kidney disease. A number of soluble mediators initiate a variety of pathophysiological processes as kidney injury evolves. In this chapter, we will discuss the pathogenesis of AKI in light of new information concerning injury and repair, and focus on the controversies arising from emerging evidence.