title: 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.
authors.affiliation: Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland; hrabb1@jhmi.edu.
authors.forename: Hamid
authors.initials: H
authors.lastname: Rabb
authors.affiliation: Regenerative Medicine Institute, School of Medicine, College of Medicine Nursing and Health Sciences, National University of Ireland, Galway, Ireland;
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Griffin
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, La Jolla, California;
authors.forename: Dianne B
authors.initials: DB
authors.lastname: McKay
authors.affiliation: Division of Nephrology, University of Virginia School of Medicine, Charlottesville, Virginia;
authors.forename: Sundararaman
authors.initials: S
authors.lastname: Swaminathan
authors.affiliation: Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands;
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
authors.affiliation: Division of Nephrology, University of Virginia School of Medicine, Charlottesville, Virginia;
authors.forename: Mitchell H
authors.initials: MH
authors.lastname: Rosner
authors.affiliation: Center for Critical Care Nephrology and Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania; and.
authors.forename: John A
authors.initials: JA
authors.lastname: Kellum
authors.affiliation: Department of Nephrology Dialysis and Transplantation, Saint Bortolo Hospital and the International Renal Research Institute, Vicenza, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ronco
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications* / Q000276:immunology; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000209:etiology* / Q000628:therapy; D007668:Kidney / Q000276:immunology
keywords: acute renal failure; clinical nephrology; immunology; pathophysiology of; renal disease and progression