Proteomics reveals biomarkers for the diagnosis and treatment of septic kidney injury

Background Sepsis-associated acute kidney injury (SA-AKI) is a severe and life-threatening disease with high incidence and mortality rates among ICU patients. However, currently, there is still a lack of effective biomarkers for early diagnosis and treatment of kidney injury in septic patients. Methods In a multi-center prospective cohort study, 37 sepsis patients (sepsis-AKI, n = 19; sepsis-NoAKI, n = 18) and 31 healthy controls were enrolled. Peripheral blood samples were analyzed by protein mass spectrometry, and principal component analysis (PCA) was used to remove outliers. Differentially expressed proteins were identified based on p < 0.05 and |log2 fold change|>1, then functionally enriched using DAVID. An additional validation cohort of 65 sepsis patients ((sepsis-AKI, n = 38; sepsis-NoAKI, n = 27) from three other centers was used to further validate the target proteins. ELISA and ROC curve analysis were performed to evaluate the diagnostic accuracy of the target proteins for SA-AKI and the need for continuous renal replacement therapy (CRRT), using the area under the ROC curve (AUC) as the performance metric. Results Ultimately, 7 proteins were differently expressed between the two groups, with 6 of them being significantly up-regulated and 1 being significantly down-regulated. Functional enrichment analysis showed that the selected differentially expressed proteins were mainly involved in immune responses, complement activation, coagulation cascades, and neutrophil degranulation. Further external validation showed that the AUC values of CST3, B2M, IGFBP4, CFD, and CD59 in diagnosing SA-AKI were all above 0.7, and there were significant differences between the two groups (P < 0.05). For whether or not to receive CRRT treatment, IGFBP4 was found to have good predictive value, with an AUC of 0.84. Conclusions This study suggests that CST3, B2M, IGFBP4, CFD, and CD59 may serve as potential biomarkers for the diagnosis of SA-AKI, with IGFBP4 specifically aiding in determining whether CRRT treatment is necessary.