Immunopathogenesis of Acute Kidney Injury

Abstract

Pathophysiologically, the classification of acute kidney injury (AKI) can be divided into three categories: (1) prerenal, (2) intrinsic, and (3) postrenal. Emerging evidence supports the involvement of renal tubular epithelial cells and the innate and adaptive arms of the immune system in the pathogenesis of intrinsic AKI. Pro-inflammatory damage-associated molecular patterns, pathogen-associated molecular patterns, hypoxia inducible factors, toll-like receptors, complement system, oxidative stress, adhesion molecules, cell death, resident renal dendritic cells, neutrophils, T and B lymphocytes, macrophages, natural killer T cells, cytokines, and secreted chemokines contribute to the immunopathogenesis of AKI. However, other immune cells and pathways such as M2 macrophages, regulatory T cells, progranulin, and autophagy exhibit anti-inflammatory properties and facilitate kidney tissue repair after AKI. Thus, therapies for AKI include agents such as anti-inflammatory (e.g., recombinant alkaline phosphatase), antioxidants (iron chelators), and apoptosis inhibitors. In preclinical toxicity studies, drug-induced kidney injury can be seen after exposure to a nephrotoxicant test article due to immune mechanisms and dysregulation of innate, and/or adaptive cellular immunity. The focus of this review will be on intrinsic AKI, as it relates to the immune and renal systems cross talks focusing on the cellular and pathophysiologic mechanisms of AKI.

Autophagy and Inflammation Regulation in Acute Kidney Injury

“…Our review suggests that the potential of autophagy to restrict the detrimental effects of inflammation might add to its positive effects in inflammation alleviation (Djavaheri-Mergny et al, 2007). Novel therapeutic interventions designed to enhance autophagy might represent an attractive strategy to overcome insufficiencies in autophagy associated with inflammatory dysregulation during AKI (Duann et al, 2016;Jia et al, 2018;Radi, 2018). Intervention strategies to induce autophagy in various AKI models include the use of autophagy activators, such as rapamycin or its analogs, and autophagy inhibitors, such as chloroquine or 3-MA, both of which have been explored as therapeutic agents in AKI (Djavaheri-Mergny et al, 2007).…”

Complete blood count in acute kidney injury prediction: a narrative review

“…The immunopathogenesis of AKI involves a complex interaction of damage-associated molecular patterns, pathogen-associated molecular patterns, oxidative stress, hypoxia inducible factor, complement system, dendritic cells, neutrophils, lymphocytes, macrophages, platelets, and cytokines [28–31].…”

Mesenchymal Stromal Cell Uses for Acute Kidney Injury—Current Available Data and Future Perspectives: A Mini-Review

“…These peroxynitrites have a vasoconstrictive effect, which can aggravate the ischemic and inflammatory damage ( 11 ). Lymphocytes enhance AKI by releasing IL-17, a proinflammatory cytokine that also increases vascular permeability ( 11 , 17 , 18 ). In contrast, M2 macrophages and regulatory T cells are essential for suppressing the overactivated inflammatory response and for regenerating damaged renal tissue and are detected while recovering from the acute insult ( 9 ).…”