Septic acute kidney injury: molecular mechanisms and the importance of stratification and targeting therapyReport as inadecuate




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Critical Care

, 18:501

First Online: 02 September 2014

Abstract

The most common cause of acute kidney injury AKI in hospitalized patients is sepsis. However, the molecular pathways and mechanisms that mediate septic AKI are not well defined. Experiments performed over the past 20 years suggest that there are profound differences in the pathogenesis between septic and ischemic AKI. Septic AKI often occurs independently of hypoperfusion, and is mediated by a concomitant pro- and anti-inflammatory state that is activated in response to various pathogen-associated molecular patterns, such as endotoxin, as well as damage-associated molecular patterns. These molecular patterns are recognized by Toll-like receptors TLRs found in the kidney, and effectuate downstream inflammatory pathways. Additionally, apoptosis has been proposed to play a role in the pathogenesis of septic AKI. However, targeted therapies designed to mitigate the above aspects of the inflammatory state, TLR-related pathways, and apoptosis have failed to show significant clinical benefit. This failure is likely due to the protean nature of septic AKI, whereby different patients present at different points along the immunologic spectrum. While one patient may benefit from targeted therapy at one end of the spectrum, another patient at the other end may be harmed by the same therapy. We propose that a next important step in septic AKI research will be to identify where patients lie on the immunologic spectrum in order to appropriately target therapies at the inflammatory cascade, TLRs, and possibly apoptosis.

AbbreviationsAKIAcute kidney injury

CIConfidence interval

DAMPDamage-associated molecular pattern

GFRGlomerular filtration rate

GM-CSFGranulocyte-macrophage colony-stimulating factor

IFNInterferon

ILInterleukin

LPSLipopolysaccharide

NFNuclear factor

PAMPPathogen-associated molecular pattern

PGC-1αPPARγ coactivator-1α

SOFASequential Organ Failure Assessment

TLRToll-like receptor

TNFTumor necrosis factor

TNFRTumor necrosis factor receptor

Electronic supplementary materialThe online version of this article doi:10.1186-s13054-014-0501-5 contains supplementary material, which is available to authorized users.

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Author: Eric D Morrell - John A Kellum - Núria M Pastor-Soler - Kenneth R Hallows

Source: https://link.springer.com/



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