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Inflammation in AKI: Current Understanding, Key Questions, and Knowledge Gaps.


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.

SUBMITTER: Rabb H 

PROVIDER: S-EPMC4731128 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Inflammation in AKI: Current Understanding, Key Questions, and Knowledge Gaps.

Rabb Hamid H   Griffin Matthew D MD   McKay Dianne B DB   Swaminathan Sundararaman S   Pickkers Peter P   Rosner Mitchell H MH   Kellum John A JA   Ronco Claudio C  

Journal of the American Society of Nephrology : JASN 20151111 2


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  ...[more]

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