Abstract
Acute kidney injury (AKI) is a frequent complication of sepsis and contributes to increased mortality. Discovery of reliable biomarkers could enable identification of individuals with high AKI risk as well as early AKI detection and AKI progression monitoring. However, the current methods are insensitive and non-specific. This study aimed to identify new biomarkers through label-free mass spectrometry (MS) analysis of a sepsis model induced by cecal ligation and puncture (CLP). Urine samples were collected from septic rats at 0, 3, 6, 12, 24, and 48 h. Protein isolated from urine was subjected to MS. Immunoregulatory biological processes, including immunoglobin production and wounding and defense responses, were upregulated at early time points. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses identified 77 significantly changed pathways. We further examined the consistently differentially expressed proteins to seek biomarkers that can be used for early diagnosis. Notably, the expression of PARK7 and CDH16 were changed in a continuous manner and related to the level of Scr in urine from patients. Therefore, PARK7 and CDH16 were confirmed to be novel biomarkers after validation in sepsis human patients. In summary, our study analyzed the proteomics of AKI at multiple time points, elucidated the related biological processes, and identified novel biomarkers for early diagnosis of sepsis-induced AKI, and our findings provide a theoretical basis for further research on the molecular mechanisms.
Highlights
Sepsis is associated with up to 50% of Acute kidney injury (AKI), and up to 60% of septic patients have AKI complications (Uchino et al, 2005; Bagshaw et al, 2009)
This study aimed to identify new biomarkers through label-free mass spectrometry (MS) analysis of a sepsis model induced by cecal ligation and puncture (CLP)
We further examined the consistently differentially expressed proteins to seek biomarkers that can be used for early diagnosis
Summary
Sepsis is associated with up to 50% of AKIs, and up to 60% of septic patients have AKI complications (Uchino et al, 2005; Bagshaw et al, 2009). Biomarkers have been proven to be important tools for current and future AKI research and clinical management (Griffin et al, 2019). Diagnosis of sepsis-induced AKI will enable appropriate and timely treatment, which may contribute to better outcomes of AKI (Bagshaw et al, 2009). Researchers have been searching for new biomarkers to diagnose AKI with a novel detection technology.
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