title: Targeting Inflammation in So-Called Acute Kidney Injury.
abstract: The clinical category of acute kidney injury includes a wide range of completely different disorders, many with their own pathomechanisms and treatment targets. In this review we focus on the role of inflammation in the pathogenesis of acute tubular necrosis (ATN). We approach this topic by first discussing the role of the immune system in the different phases of ATN (ie, early and late injury phase, recovery phase, and the long-term outcome phase of an ATN episode). A more detailed discussion focuses on putative therapeutic targets among the following mechanisms and mediators: oxidative stress and reactive oxygen species-related necroinflammation, regulated cell death-related necroinflammation, immunoregulatory lipid mediators, cytokines and cytokine signaling, chemokines and chemokine signaling, neutrophils and neutrophils extracellular traps (NETs) associated neutrophil cell death, called NETosis, extracellular histones, proinflammatory mononuclear phagocytes, humoral mediators such as complement, pentraxins, and natural antibodies. Any prioritization of these targets has to take into account the intrinsic differences between rodent models and human ATN, the current acute kidney injury definitions, and the timing of clinical decision making. Several conceptual problems need to be solved before anti-inflammatory drugs that are efficacious in rodent ATN may become useful therapeutics for human ATN.
authors.affiliation: Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Shrikant R
authors.initials: SR
authors.lastname: Mulay
authors.affiliation: Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Holderied
authors.affiliation: Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany.
authors.forename: Santhosh V
authors.initials: SV
authors.lastname: Kumar
authors.affiliation: Nephrologisches Zentrum, Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Munich, Germany. Electronic address: hjanders@med.uni-muenchen.de.
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Anders
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism*; D019468:Disease Management; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000628:therapy
chemical_list: D016207:Cytokines
keywords: AKI; injury; necroptosis; neutrophil extracellular traps; regulated necrosis; therapy