title: 'Biologic memory' in response to acute kidney injury: cytoresistance, toll-like receptor hyper-responsiveness and the onset of progressive renal disease.
abstract: Following the induction of ischemic or toxin-mediated acute kidney injury (AKI), cellular adaptations occur that 're-program' how the kidney responds to future superimposed insults. This re-programming is not simply a short-lived phenomenon; rather it can persist for many weeks, implying that a state of 'biologic memory' has emerged. These changes can be both adaptive and maladaptive in nature and they can co-exist in time. A beneficial adaptation is the emergence of acquired cytoresistance, whereby a number of physiologic responses develop that serve to protect the kidney against further ischemic or nephrotoxic attack. Conversely, some changes are maladaptive, such as a predisposition to Gram-negative or Gram-positive bacteremia due to a renal tubular up-regulation of toll-like receptor responses. This latter change culminates in exaggerated cytokine production, and with efflux into the systemic circulation, extra-renal tissue injury can result (so-called 'organ cross talk'). Another maladaptive response is a persistent up-regulation of pro-inflammatory, pro-fibrotic and vasoconstrictive genes, culminating in progressive renal injury and ultimately end-stage renal failure. The mechanisms by which this biologic re-programming, or biologic memory, is imparted remain subjects for considerable debate. However, injury-induced, and stable, epigenetic remodeling at pro-inflammatory/pro-fibrotic genes seems likely to be involved. The goal of this editorial is to highlight that the so-called 'maintenance phase' of acute renal failure is not a static one, somewhere between injury induction and the onset of repair. Rather, this period is one in which the induction of 'biologic memory' can ultimately impact renal functional recovery, extra-renal injury and the possible transition of AKI into chronic, progressive renal disease.
authors.affiliation: The Fred Hutchinson Cancer Research Center, and the University of Washington, Seattle, WA, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Zager
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000276:immunology*; D000818:Animals; D019610:Cytoprotection; D018450:Disease Progression; D004361:Drug Tolerance; D006801:Humans; D006967:Hypersensitivity; D007156:Immunologic Memory / Q000276:immunology*; D007676:Kidney Failure, Chronic / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D051193:Toll-Like Receptors
keywords: acute kidney injury; chronic kidney disease; epigenetics; ischemic preconditioning; sepsis syndrome