(TIMP2) x (IGFBP7) as early renal biomarker for the prediction of acute kidney injury in aortic surgery (TIGER). A single center observational study

Abstract

Objective Postoperative acute kidney injury (po-AKI) is frequently observed after major vascular surgery and impacts on mortality rates. Early identification of po-AKI patients using the novel urinary biomarkers insulin-like growth factor-binding-protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) might help in early identification of individuals at risk of AKI and enable timely introduction of preventative or therapeutic interventions with the aim of reducing the incidence of po-AKI. We investigated whether biomarker-based monitoring would allow for early detection of po-AKI in patients undergoing abdominal aortic interventions. Methods In an investigator-initiated prospective single-center observational study in a tertiary care academic center, adult patients with emergency/ elective abdominal aortic repair were included. Patients were tested for concentrations of urinary (TIMP-2) x (IGFBP7) at baseline, after surgical interventions (PO), and in the mornings of the first postoperative day (POD1). The primary endpoint was a difference in urinary (TIMP-2) x (IGFBP7) levels at POD1 in patients with/ without po-AKI (all KDIGO stages, po-AKI until seven days after surgery). Secondary endpoints included sensitivity/ specificity analyses of previously proposed cut-off levels and clinical outcome measures (e.g. need for renal replacement therapy). Results 93 patients (n = 71 open surgery) were included. Po-AKI was observed in 33% (31/93) of patients. Urinary (TIMP-2) x (IGFBP7) levels at POD1 did not differ between patients with/ without AKI (median 0.39, interquartile range [IQR] 0.13–1.05 and median 0.23, IQR 0.14–0.53, p = .11, respectively) and PO (median 0.2, IQR 0.08–0.42, 0.18, IQR 0.09–0.46; p = .79). Higher median (TIMP-2) x (IGFBP7) levels were noted in KDIGO stage 3 pAKI patients at POD1 (3.75, IQR 1.97–6.92; p = .003). Previously proposed cutoff levels (0.3, 2) showed moderate sensitivity/ specificity (0.58/0.58 and 0.16/0.98, respectively). Conclusion In a prospective monocentric observational study in patients after abdominal aortic repair, early assessment of urinary (TIMP-2) x (IGFBP7) did not appear to have adequate sensitivity/ specificity to identify patients that later developed postoperative AKI. Clinicaltrials.gov NCT03469765, registered March 19, 2018.

Comprehensive analysis of expression, prognosis and immune infiltration for TIMPs in glioblastoma

“…TIMP-2 is a unique member of the TIMP family because it directly inhibits endothelial cell proliferation instead of metalloproteinase activity [ 50 ]. TIMP2 has recently made adequate progress among biomarkers of renal injury [ 51 , 52 ]. Regarding cancer, the current findings show that the role of TIMP2 in prognosis depends on the tissue of origin of the tumor [ 53 ].…”

Burn-Induced Acute Kidney Injury–Two-Lane Road: From Molecular to Clinical Aspects

“…It also shows the ability and sensitivity to predict AKI development upon admission, correlating with TBSA, APACHE II score, and rhabdomyolysis presence. Furthermore, KIM-1 and IL-18 can be used to predict AKI development in the post-burn period [ 89 , 116 ]. Further studies in this field are required in order to show the usefulness of this molecule in severe burn patients.…”

Predictive Value of Urinary Cell Cycle Arrest Biomarkers for All Cause-Acute Kidney Injury: A meta-analysis

“…Moreover, two studies were unable to extract a 2 2 table data, but only AUROC prediction values [16,17]. Finally, 20 studies were included in the quantitative analysis (Figure 1) [10,11,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35].…”

“…Three studies used RIFLE (risk, injury, failure, loss, end-stage kidney disease) [10,18,20], and the remaining 17 used the Kidney Disease Improving Global Outcomes (KDIGO) criteria for AKI. Most studies used a minimal threshold for AKI (KDIGO stage 1) [11,[25][26][27][28][29][30][31][32][33][34][35], whereas 5 studies set higher thresholds (KDIGO stage 2-3) [19,[21][22][23][24].…”