Inflammation in AKI

Abstract

Inflammation is a complex biologic response that is essential for eliminating microbial pathogens and repairing tissue after injury. AKI associates with intrarenal and systemic inflammation; thus, improved understanding of the cellular and molecular mechanisms underlying the inflammatory response has high potential for identifying effective therapies to prevent or ameliorate AKI. In the past decade, much knowledge has been generated about the fundamental mechanisms of inflammation. Experimental work in small animal models has revealed many details of the inflammatory response that occurs within the kidney after typical causes of AKI, including insights into the molecular signals released by dying cells, the role of pattern recognition receptors, the diverse subtypes of resident and recruited immune cells, and the phased transition from destructive to reparative inflammation. Although this expansion of the basic knowledge base has increased the number of mechanistically relevant targets of intervention, progress in developing therapies that improve AKI outcomes by modulation of inflammation remains slow. In this article, we summarize the most important recent developments in understanding the inflammatory mechanisms of AKI, highlight key limitations of the commonly used animal models and clinical trial designs that may prevent successful clinical application, and suggest priority approaches for research toward clinical translation in this area.

Red Blood Cell Distribution Width is an Independent Predictor of AKI and Mortality in Patients in the Coronary Care Unit

“…First, inflammation inhibits bone marrow function and iron metabolism [26, 27], and proinflammatory cytokines have been shown to inhibit erythropoietin-induced erythrocyte maturation and proliferation and to downregulate erythropoietin receptor expression, changes associated with increases in RDW [28]. In addition, AKI is known to be associated with intrarenal and systemic inflammation [29]. Forhecz et al .…”

Cellular and Molecular Mechanisms of AKI

“…45 Many questions relating to the role of receptors in AKI remain unanswered, including the sources of the putative ligands, mechanisms of receptor activation, and signaling pathways involved in protection from injury or involved with epithelial repair. The important role of receptors involved in innate immunity (like TLRs) is discussed in a related Journal of the American Society of Nephrology review by Rabb et al 46 Cell Cycle Under normal physiologic conditions, cell proliferation in kidneys is limited to a small percentage of cells, indicating that most cells are quiescent at the G 0 phase of the cell cycle at any given point in time. In AKI, there is notable cell proliferation, especially in the damaged renal tubules.…”

Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney

“…Inflammation is a crucial contributor to cellular injury and malfunction (2,3,6,7), and inflammatory cell infiltration is commonly observed in chronic diseases. Although most inflammatory cells are not spatially and functionally organized, chronic infiltrates sometimes organize into clusters that are enriched in T and B cells.…”