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Septic acute kidney injury: Molecular mechanisms and the importance of stratification and targeting therapy

Morrell, ED and Kellum, JA and Pastor-Soler, NM and Hallows, KR (2014) Septic acute kidney injury: Molecular mechanisms and the importance of stratification and targeting therapy. Critical Care, 18 (5). ISSN 1364-8535

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Abstract

© 2014 Morrell et al.; licensee BioMed Central Ltd. 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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Morrell, ED
Kellum, JAkellum@pitt.eduKELLUM0000-0003-1995-2653
Pastor-Soler, NM
Hallows, KRhallows@pitt.eduHALLOWS
Date: 2 September 2014
Date Type: Publication
Journal or Publication Title: Critical Care
Volume: 18
Number: 5
DOI or Unique Handle: 10.1186/s13054-014-0501-5
Schools and Programs: School of Medicine > Cell Biology
School of Medicine > Critical Care Medicine
School of Medicine > Medicine
Refereed: Yes
ISSN: 1364-8535
Article Type: Review
Date Deposited: 19 Sep 2016 15:52
Last Modified: 04 Feb 2019 15:57
URI: http://d-scholarship.pitt.edu/id/eprint/29497

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