Triggers of inflammation after renal ischemia/reperfusion

Abstract

Renal ischemia/reperfusion (I/R) is a common cause of acute renal failure (ARF). Ischemic ARF is associated with tubulointerstitial inflammation, and studies using animal models have demonstrated that the inflammatory response to I/R exacerbates the resultant renal injury. Ischemic ARF involves complement activation, the generation of cytokines and chemokines within the kidney, and infiltration of the kidney by leukocytes. Recent work has revealed some of the events and signals that trigger the inflammatory response to aseptic, hypoxic injury of the kidney. In many ways, the inflammatory reaction to this injury resembles that seen during ascending urinary infection, and it may represent a general response of the tubular epithelial cells (TECs) to stress or injury. A greater understanding of the signals that trigger the inflammatory response may permit the development of effective therapies to ameliorate ischemic ARF.

Figure 1

Triggers of inflammation after aseptic tissue injury. Tissue injury can initiate inflammation by several mechanisms which may occur simultaneously. Cellular injury can cause the release or exposure of inflammatory factors. Stress or injury can induce the active synthesis of pro-inflammatory signals. Immune system receptors may recognize altered or exposed surface structures. Decreased expression of inhibitory factors may permit uncontrolled activation of inflammatory cells or systems.

Figure 2

Tubular epithelial cells generate inflammatory signals in response to injury or stress. In response to ischemia, epithelial cells favor complement activation by synthesizing C3 and decreasing their surface expression of Crry. Expression of the C5a receptor and TLRs 2 and 4 increase. Anaphylatoxins and ligation of the TLRs induce the cells to produce C-X-C chemokines.