Jan Waskowski1,2, Carmen A Pfortmueller2, Noelle Schenk2, Roman Buehlmann3, Juerg Schmidli3, Gabor Erdoes1, Joerg C Schefold2. 1. Department of Anesthesiology and Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 2. Department of Intensive Care Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. 3. Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
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.
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.
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