Discovery and validation of miR-452 as an effective biomarker for acute kidney injury in sepsis.

Theranostics
Zhiwen LiuZheng Dong

Abstract

Rationale: Sepsis is the cause of nearly half of acute kidney injury (AKI) and, unfortunately, AKI in sepsis is associated with unacceptably high rates of mortality. Early detection of AKI would guide the timely intervention and care of sepsis patients. Currently, NephroCheck, based on urinary [TIMP2]*[IGFBP7], is the only FDA approved test for early detection of AKI, which has a relatively low sensitivity for sepsis patients. Methods: In vitro, BUMPT (Boston University mouse proximal tubular cell line) cells were treated with lipopolysaccharides (LPS). In vivo, sepsis was induced in mice by LPS injection or cecal ligation and puncture (CLP). To validate the biomarker potential of miR-452, serum and urinary samples were collected from 47 sepsis patients with AKI, 50 patients without AKI, and 10 healthy subjects. Results: miR-452 was induced in renal tubular cells in septic AKI, and the induction was shown to be mediated by NF-κB. Notably, serum and urinary miR-452 increased early in septic mice following LPS or CLP treatment, prior to detectable renal dysfunction or tissue damage. Sepsis patients with AKI had significantly higher levels of serum and urinary miR-452 than the patients without AKI. Spearman's test demonstrated a r...Continue Reading

Methods Mentioned

BETA
Fluorescence
ELISA
PCR
immunoprecipitation
confocal microscopy
ChIP

Software Mentioned

miRanda
SPSS
GraphPad Prism
NephroCheck®
TargetScan

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