The innate immune response in ischemic acute kidney injury

Abstract

Kidney ischemia reperfusion injury is a major cause of morbidity in both allograft and native kidneys. Ischemia reperfusion-induced acute kidney injury is characterized by early, alloantigen-independent inflammation. Major components of the innate immune system are activated and participate in the pathogenesis of acute kidney injury, plus prime the allograft kidney for rejection. Soluble members of innate immunity implicated in acute kidney injury include the complement system, cytokines, and chemokines. Toll-like receptors (TLRs) are also important contributors. Effector cells that participate in acute kidney injury include the classic innate immune cells, neutrophils and macrophages. Recent data has unexpectedly identified lymphocytes as participants of early acute kidney injury responses. In this review, we will focus on immune mediators that participate in the pathogenesis of ischemic acute kidney injury.

Figure 1. Overview of early immune response occurring in post-ischemic kidneys

In experimental ischemia reperfusion-induced acute kidney injury models, ischemic insult occurs first and then reperfusion initiates inflammation in post-ischemic kidneys with entry of blood containing major cellular components of innate immunity, plus lymphocytes. Leukocytes including neutrophils, macrophages and lymphocytes traffic into post-ischemic kidneys. Cytokines and complement system also contribute to renal injury. Early injury events take place both at the level of the microvasculature, and then in the tubular interstitial space. Renal microcirculation is interfered by plugging with leukocytes and platelets and each immune component act in concert causing robust inflammatory responses in the tubular interstitial space.