Document Detail


'Biologic memory' in response to acute kidney injury: cytoresistance, toll-like receptor hyper-responsiveness and the onset of progressive renal disease.
MedLine Citation:
PMID:  23761460     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Richard A Zager
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2013-06-11
Journal Detail:
Title:  Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association     Volume:  28     ISSN:  1460-2385     ISO Abbreviation:  Nephrol. Dial. Transplant.     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-09-09     Completed Date:  2014-04-03     Revised Date:  2014-08-03    
Medline Journal Info:
Nlm Unique ID:  8706402     Medline TA:  Nephrol Dial Transplant     Country:  England    
Other Details:
Languages:  eng     Pagination:  1985-93     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acute Kidney Injury / complications,  immunology*
Animals
Cytoprotection
Disease Progression
Drug Tolerance*
Humans
Hypersensitivity*
Immunologic Memory / immunology*
Kidney Failure, Chronic / etiology*,  metabolism,  pathology
Toll-Like Receptors / metabolism*
Grant Support
ID/Acronym/Agency:
DK083310/DK/NIDDK NIH HHS; DK38432/DK/NIDDK NIH HHS; R01 DK038432/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Toll-Like Receptors
Comments/Corrections

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