Sepsis-induced
acute kidney injury (SI-AKI) is a serious condition in
critically ill patients. Currently, the diagnosis is based on either elevated serum
creatinine levels or
oliguria, which partially contribute to delayed recognition of AKI. Metabolomics is a potential approach for identifying small molecule
biomarkers of
kidney diseases. Here, we studied serum metabolomics alterations in rats with
sepsis to identify early
biomarkers of
sepsis and SI-AKI. A rat model of SI-AKI was established by
intraperitoneal injection of
lipopolysaccharide (LPS). Thirty Sprague-Dawley (SD) rats were randomly divided into the control (CT) group and groups treated for 2 hours (LPS2) and 6 hours (LPS6) with LPS (10 rats per group). Nontargeted metabolomics screening was performed on the serum samples from the control and SI-AKI groups. Combined multivariate and univariate analysis was used for pairwise comparison of all groups to identify significantly altered serum metabolite levels in early-stage AKI in rats with
sepsis. Orthogonal partial least squares discriminant analysis (OPLS-DA) showed obvious separation between the CT and LPS2 groups, CT and LPS6 groups, and LPS2 and LPS6 groups. All comparisons of the groups identified a series of differential metabolites according to the threshold defined for potential
biomarkers. Intersections and summaries of these differential metabolites were used for pathway enrichment analysis. The results suggested that
sepsis can cause an increase in systemic aerobic and anaerobic metabolism, an impairment of the
oxygen supply, and uptake and abnormal
fatty acid metabolism. Changes in the levels of
malic acid,
methionine sulfoxide, and
petroselinic acid were consistently measured during the progression of
sepsis. The development of
sepsis was accompanied by the development of AKI, and these metabolic disorders are directly or indirectly related to the development of SI-AKI.