Novel Blood Cytokine‐Based Model for Predicting Severe Acute Kidney Injury and Poor Outcomes After Cardiac Surgery

Figure 1. Association of 32 blood cytokines and acute kidney injury (AKI) after cardiac surgery. A, Hierarchical clustering of samples based on the 32 cytokines among the non‐AKI, mild‐AKI and severe AKI groups. B, Forest plot of univariate logistic analysis of the 32 cytokines and severe AKI after cardiac surgery. AKI was defined by the AKIN criteria: mild AKI=AKIN stage 1, severe AKI=AKIN stage 2/3. AKI indicates acute kidney injury; IFN, interferon; IL, interleukin; MIP, macrophage inflammatory protein; TNF, tumor necrosis factor; CTACK, cutaneous T‐cell‐attracting chemokine; FGFa, acidic fibroblast growth factor, G‐CSF, granulocyte‐colony‐stimulating factor; HGF, hepatocyte growth factor; IP‐10, interferon gamma‐induced protein‐10, MCP, monocyte chemotactic protein; M‐CSF, macrophage‐colony stimulating factor; MIF, migration inhibitory factor; MIG, monokine induced by interferon‐gamma ; SCF, stem cell factor; SCGF‐β, stem cell growth factor‐beta; SDF‐1α, stromal‐derived factor‐1 alpha.

Figure 2. Variation in the concentrations of the selected cytokines between the severe and non‐severe AKI (acute kidney injury) groups in the screening and validation cohorts. A, comparison of interferon‐γ between the severe and non‐severe AKI groups in the screening cohort. B, A comparison of interferon‐γ between the severe and non‐severe AKI groups in the validation cohort. C, Comparison of interleukin‐16 between the severe and non‐severe AKI groups in the screening cohort. D, Comparison of interleukin‐16 between the severe and non‐severe AKI groups in the validation cohort. E, Comparison of MIP‐1α (macrophage inflammatory protein‐1 alpha) between the severe and non‐severe AKI groups in the screening cohort. F, Comparison of MIP‐1α between the severe and non‐severe AKI groups in the validation cohort. In the violin plots, the horizontal dotted lines indicate the first quartile and the third quartile of the cytokine levels, and the horizontal dashed line within the violin represents the median cytokine levels. Statistical significance was determined by a non‐parametric test (***P<0.0001). AKI indicates acute kidney injury; IFN‐γ , interferon‐gamma; IL‐16, interleukin‐16; and MIP‐1α,…

Figure 3. Decision curve analysis (DCA) and prognostic nomogram of the clinical factor‐based model. A, The DCA curve for comparing the novel cytokine‐based model and clinical factors in the screening cohort. B, The DCA curve for comparing the novel cytokine‐based model and clinical factors in the validation cohort. C, The DCA curve for comparing the novel cytokine‐based model and established biomarkers in the screening cohort. D, The DCA curve for comparing the novel cytokine model and established biomarkers in the validation cohort. The novel cytokine‐based model included interferon‐γ, interleukin‐16, and macrophage inflammatory protein‐1α. Clinical factors included comorbidity of hypertension, concomitant surgery, and cardiopulmonary bypass time. Established biomarkers included monocyte chemotactic protein‐1 and tumor necrosis factor‐α. The net benefit of the multibiomarker model and clinical predictors was plotted against the threshold probability; the horizontal axis represents the threshold value, which is the reference probability of whether a patient receives treatment, and the vertical axis represents the net benefit rate after the advantages are subtracted from the disadvantages.…

Figure 4. Performance of cytokines for predicting severe acute kidney injury and composite events. The C‐statistics of cytokines (interferon‐γ, interleukin‐16, MIP‐1α [macrophage inflammatory protein‐1 alpha]) for predicting severe acute kidney injury in the screening cohort (A) and the validation cohort (B). The C‐statistics of biomarkers (interferon‐γ, interleukin‐16, MIP‐1α) for predicting composite events in the screening cohort (C) and the validation cohort (D). AKI indicates acute kidney injury; IFN‐γ , interferon‐gamma; IL‐16, interleukin‐16; and MIP‐1α, macrophage inflammatory protein‐1 alpha.

Figure 5. Performance of cytokines for predicting severe acute kidney injury and composite events in age/sex stratified groups. Left: The C‐statistics and 95% CIs of cytokines (interferon‐γ, interleukin‐16, MIP‐1α [macrophage inflammatory protein‐1 alpha]) for predicting severe acute kidney injury in the male and female groups as well as the young and middle‐aged groups (aged <60 years) and the older group (aged ≥60 years). Right: The C‐statistics and 95% CIs of biomarkers (interferon‐γ, interleukin‐16, MIP‐1α) for predicting composite events in different subgroups. AKI indicates acute kidney injury; IFN‐γ , interferon‐gamma; IL‐16, interleukin‐16; and MIP‐1α, macrophage inflammatory protein‐1 alpha.