PUBLICATION
Sepsis-Associated Acute Kidney Injury: A Problem Deserving of New Solutions
- Authors
- Kellum, J.A., Wen, X., de Caestecker, M.P., Hukriede, N.A.
- ID
- ZDB-PUB-190425-22
- Date
- 2019
- Source
- Nephron 143(3): 174-178 (Review)
- Registered Authors
- Hukriede, Neil, Wen, Xiao-Yan
- Keywords
- Embryonic kidney progenitor cell, Renal repair, Sepsis-associated acute kidney injury
- MeSH Terms
-
- Acute Kidney Injury/etiology*
- Acute Kidney Injury/pathology
- Acute Kidney Injury/therapy*
- Animals
- Histone Deacetylase Inhibitors/therapeutic use
- Humans
- Kidney/pathology
- Regeneration
- Sepsis/complications*
- Sepsis/pathology
- Sepsis/therapy*
- PubMed
- 31018211 Full text @ Nephron
Citation
Kellum, J.A., Wen, X., de Caestecker, M.P., Hukriede, N.A. (2019) Sepsis-Associated Acute Kidney Injury: A Problem Deserving of New Solutions. Nephron. 143(3):174-178.
Abstract
Sepsis-associated acute kidney injury (S-AKI) significantly worsens patient prognosis, and recent evidence suggests that the injury process begins early and may be sustained by therapies used to treat the sepsis (e.g., fluids resuscitation, antibiotics). While efforts to develop less-injurious treatments are making progress, some degree of secondary injury is to be expected. So too is the inevitable nature of organ injury, which is often present at the time the patient seeks medical attention. We recently found that most patients presenting with septic shock and developing AKI had evidence of kidney damage at the time of, or within 24 h of their admission. In such patients, prevention is not a viable option, as injury has already occurred by the time of presentation. Since S-AKI patients are at increased risk of developing chronic kidney disease, a fundamental target for interventions in S-AKI is to prevent fibrosis (maladaptive repair) while stimulating regeneration (proliferation of viable epithelial cells). Using a pathway-agnostic, proliferation-based phenotypic assay, we discovered phenylthiobutanoic acid, a small molecule histone deacetylase inhibitor, that enhances renal recovery and reduces fibrosis in both zebrafish and mouse models of AKI.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping