Correlation Engine 2.0
Clear Search sequence regions

  • c57bl mice (1)
  • CCL3 (4)
  • children (1)
  • ligand (1)
  • plasma (1)
  • sepsis (20)
  • serum (1)
  • Sizes of these terms reflect their relevance to your search.

    Sepsis-associated acute kidney injury (SA-AKI) is a frequent complication of sepsis, yet the pathophysiologic mechanisms of SA-AKI are incompletely understood. PERSEVERE is a clinically validated serum biomarker panel with high sensitivity in predicting mortality from sepsis, and recent evidence suggests it can also predict severe, persistent SA-AKI at day 3 of hospitalization among septic children. We developed a murine model of PERSEVERE (mPERSEVERE) to further interrogate the sepsis-related biological underpinnings of SA-AKI using candidate biomarkers within mPERSEVERE. Eight-week-old C57BL/6 male mice underwent induction of sepsis by cecal ligation and puncture (CLP). mPERSEVERE biomarkers were collected at 8-hours and kidneys were harvested at 24-hours post-CLP Classification and regression tree analysis (CART) was used to generate a SA-AKI predictive model. Kidney gene expression levels of candidate biomarkers were quantified using real time polymerase chain reaction. Thirty- five mice underwent CLP Among mice identified by mPERSEVERE as high-risk for mortality, 70% developed SA-AKI at 24-hours compared to 22% of low-risk mice. CART analysis identified two mPERSEVERE biomarkers-C-C motif chemokine ligand 3 (CCL3) and keratinocyte-derived chemokine (KC)-as most predictive for SA-AKI with an area under the receiver operating curve of 0.90. In mice that developed SA-AKI, renal expression of KC was significantly increased compared to mice without SA-AKI (p  = 0.013), whereas no difference was seen in renal expression of CCL3 in mice with SA-AKI vs. no SA-AKI. KC and CCL3 localized to renal tubule epithelial cells as opposed to infiltrating immune cells by immunohistochemistry. The combination of plasma CCL3+KC can predict SA-AKI development in mice at 24-hours following CLP Of these two biomarkers, only renal expression of KC is increased in mice with SA-AKI. Further studies are required to determine if KC directly contributes to the underlying pathobiology of SA-AKI. Copyright © 2022 by the Shock Society.


    James D Odum, Steve Standage, Matthew Alder, Basilia Zingarelli, Prasad Devarajan, Hector R Wong. Candidate Biomarkers for Sepsis-Associated Acute Kidney Injury Mechanistic Studies. Shock (Augusta, Ga.). 2022 May 01;57(5):687-693

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 35234208

    View Full Text