Table 2.
Summary of biomarkers used to detect SA-AKI.
| Types of biomarker | Biomarker | Source | Potential use in SA-AKI |
|---|---|---|---|
| Inflammation biomarkers | IL-6 | Mononuclear macrophages, Th2 cells, vascular endothelial cells and fibroblasts | Baseline IL-6 at admission predicted AKI in patients with severe sepsis, and IL-6 also predicts the development of AKI and need for RRT in patients with severe sepsis (100). |
| IL-18 | Monocytes, dendritic cells, macrophages and epithelial cells | In a prospective, multicenter cohort, UIL-18 independently predicted the progression of septic AKI (AUC 0.619; 95% CI, 0.525 to 0.731) (101). | |
| sTREM-1 | Activated receptors selectively expressed on the surfaces of neutrophils, macrophages, and mature monocytes | In patients with sepsis, The AUC values of plasma STREM-1 in the diagnosis and prediction of AKI (24h before diagnosis) were 0.794 and 0.746, respectively. The AUC values of urine STREM-1 were 0.707 and 0.778. ACU 0.922 was predicted 48 hours before diagnosis, and urine STREM-1 was a fairly good predictor (102). | |
| Endothelial injury biomarkers | Ang | Ang1 is mainly synthesized by paravascular sertoli cells, vascular smooth muscle cells and tumor cells; Ang2 is mainly synthesized by vascular smooth muscle cells | Ang1 has a protective effect against endotoxemia, increasing vasoconstriction and reducing pulmonary microvascular leakage associated with inflammation (103). Circulating Ang1 levels were suppressed in critically ill patients with septic shock (104). Circulating Ang-2 is a strong independent predictor of mortality in ICU dialysis-dependent AKI patients (105). |
| VE-cadherin | Vascular endothelial cell | Plasma sVE-cadherin was independently associated with AKI-RRT, suggesting that disruption of endothelial adhesion and connectivity may contribute to the pathogenesis of organ dysfunction in sepsis (106). | |
| sTM | Vascular endothelial cell | Compared with sepsis non-AKI group, sTM in SA-AKI group was significantly different (P<0.0001); Multivariate logistic regression analysis showed that sTM was an independent predictor of AKI, and AUROC was 0.758(P<0.0001) (107). | |
| Tubular injury biomarkers | NGAL | Leukocytes, loops of medullary and collecting ducts | SA-AKI patients have higher detectable plasma and urine NGAL compared with non-septic AKI patients. These differences in NGAL values in SA-AKI may have diagnostic and clinical relevance as well as pathogenetic implications (108). |
| KIM-1 | RTECs | UKIM-1 and sKIM-1 levels were significantly higher in SA-AKI than in patients without AKI. ROC of uKIM-1 and sKIM-1 for AKI prediction was 0.607 and 0.754, respectively (109). | |
| L-FABP | Liver cells; RTECs | Urinary L-FABP level may be a predictive marker of sepsis severity and mortality, and can serve as a useful biomarker for patients with sepsis complicated with AKI (109). | |
| Cys C | All nucleated cells | Urine and plasma are of value in the diagnosis and prediction of AKI occurrence (24 hours before diagnosis) in patients with SA-AKI (21). Aydogdu et al. confirmed that plasma and urine Cys-C were good markers for early diagnosis of septic associated AKI (AUCs 0.82 and 0.86, respectively) (110). However, some studies in adults and newborns have shown that sepsis has no effect on plasma or urine levels of Cys-C (111, 112). | |
| AKI risk biomarkers | [TIMP-2] • [IGFBP7] | TIMP-2 is synthesized by RTECs; IGFBP7 is expressed in almost all epithelial cells | [TIMP-2] • [IGFBP7] predicted the development of stage 2 and 3 AKI in high-risk and critically ill patients with sepsis with an AUC of 0.84. The biomarker performed similarly regardless of disease severity (SOFA score), with a sensitivity of 77.5% and specificity of 75% for severe AKI at a cut-off value of 1.0 (113). |
| Electronic alerts, electronic risk algorithms | \ | Several alarms have shown the ability to predict sepsis and AKI separately, and the combination of biochemical biomarkers may help enrich the detection and risk stratification of SA-AKI (20). |
IL-6, Interleukin-6; IL-18, Interleukin-18; sTREM-1, Soluble triggering receptor expressed myeloidcells 1; Ang, Angiopoietins; sTM, Soluble thrombomodulin; NGAL, Neutrophil gelatinase-associated lipocalin; KIM-1, Kidney Injury Molecule-1; L-FABP, Liver-type fatty acid binding protein; Cys C, Cystatin C; TIMP-2, Tissue Inhibitors Of Metalloproteinase 2; IGFBP7, Insulin-like growth factor binding protein-7.