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• W4214904585 abstract "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." @default.
• W4214904585 created "2022-03-05" @default.
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• W4214904585 date "2022-02-28" @default.
• W4214904585 modified "2023-09-27" @default.
• W4214904585 title "Candidate Biomarkers for Sepsis-Associated Acute Kidney Injury Mechanistic Studies" @default.
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• W4214904585 doi "https://doi.org/10.1097/shk.0000000000001916" @default.
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