Predicting Acute Kidney Injury in Intensive Care Unit Patients: The Role of Tissue Inhibitor of Metalloproteinases-2 and Insulin-Like Growth Factor-Binding Protein-7 Biomarkers

Leo, Laura Di; Nalesso, Federico; Garzotto, Francesco; Xie, Yun; Yang, Bo; Virzì, Grazia Maria; Passannante, Alberto; Bonato, Raffaele; Carta, M.; Giavarina, Davide; Gregori, Darío; Brendolan, Alessandra; Ferrari, Fiorenza; Ronco, Claudio

doi:10.1159/000485591

Cited by 29 publications

(19 citation statements)

References 30 publications

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“…Contrasting results regarding interventions to prevent AKI have led to disappointment regarding the use of biomarkers alone [35,36]. Nevertheless, (TIMP-2)•(IGFBP7) improved the predictive performance at ICU admission of a clinical model for AKI at any stage ( Ferrari F , submitted to Scientific Reports 2018 , [37], even if its best performance is to identify patients at risk of developing severe (stage 2–3) AKI [38–40].…”

Section: Resultsmentioning

confidence: 99%

Development and validation of quick Acute Kidney Injury-score (q-AKI) to predict acute kidney injury at admission to a multidisciplinary intensive care unit

et al. 2019

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AKI is associated with increased risk of death, prolonged length of stay and development of de-novo chronic kidney disease. The aim of our study is the development and validation of prediction models to identify the risk of AKI in ICU patients up to 7 days. We retrospectively recruited 692 consecutive patients admitted to the ICU at San Bortolo Hospital (Vicenza, Italy) from 1 June 2016 to 31 March 2017: 455 patients were treated as the derivation group and 237 as the validation group. Candidate variables were selected based on a literature review and expert opinion. Admission eGFR< 90 ml/min /1.73 mq (OR 2.78; 95% CI 1.78–4.35; p<0.001); SOFAcv ≥ 2 (OR 2.23; 95% CI 1.48–3.37; p<0.001); lactate ≥ 2 mmol/L (OR 1.81; 95% CI 1.19–2.74; p = 0.005) and (TIMP-2)•(IGFBP7) ≥ 0.3 (OR 1.65; 95% CI 1.08–2.52; p = 0.019) were significantly associated with AKI. For the q-AKI score, we stratified patients into different AKI Risk score levels: 0–2; 3–4; 5–6; 7–8 and 9–10. In both cohorts, we observed that the proportion of AKI patients was higher in the higher score levels.

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Section: Resultsmentioning

confidence: 99%

Development and validation of quick Acute Kidney Injury-score (q-AKI) to predict acute kidney injury at admission to a multidisciplinary intensive care unit

et al. 2019

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“…Among these, surgical patients were the target population, including patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass 18 , valvular, or combined surgery with cardiopulmonary bypass 19 and no cardiac surgery 20 . Meersch 21 and Gocze 22 estimated an AUC for AKI stage 1 of 0.81 and 0.85, respectively. With an estimated cut-off of 1.1 (ng/ml) 2 /1000, Wetz and colleagues were able to discriminate between patients with and without AKI on the first postoperative day with an AUC of 0.706, albeit this study did not include high risk patients and those undergoing urgent surgery 18 .…”

Section: Discussionmentioning

confidence: 99%

“…Otherwise, Di Leo et al . evaluated the value of [TIMP-2]∙[IGFBP7] to predict AKI free days in 719 critically ill patients, estimating an optimal cut-off of 0.37 (ng/ml) 2 /1000 (AUC 0.633, specificity and sensitivity 56% and 64%, respectively), thereby demonstrating that [TIMP-2]∙[IGFBP7] captures most AKI positive cases and a high number of patients who do not develop AKI 21 .…”

Section: Discussionmentioning

confidence: 99%

Routine Adoption of Urinary [IGFBP7]∙[TIMP-2] to Assess Acute Kidney Injury at Any Stage 12 hours After Intensive Care Unit Admission: a Prospective Cohort Study

Ferrari

Romero‐González

Topete

et al. 2019

Sci Rep

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The urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 ([TIMP-2]∙[IGFBP7]) have been introduced to improve risk prediction of severe acute kidney injury (AKI) within 12 hours of measurement. We performed a prospective cohort study to evaluate if the predictive value of [TIMP-2]∙[IGFBP7] for AKI might continue after 12 hours. We enrolled 442 critically ill adult patients from June to December 2016. Urine samples were collected at admission for [TIMP-2]∙[IGFBP7] measurement. Baseline patient characteristics were recorded including patients’ demographics, prior health history, and the main reason for admission to build a logistic regression model to predict AKI. AKI occurrence differed between patients with [TIMP-2]∙[IGFBP7] ≤0.3 and >0.3 (ng/ml)2/1000 (31.9% and 68.10% respectively; p < 0.001). Patients with AKI had higher biomarker values compared to those without AKI (0.66 (0.21–2.84) vs 0.22 (0.08–0.63) (ng/ml)2/1000; p < 0.001). [TIMP-2]∙[IGFBP7] at ICU admission had a lower performance in predicting AKI at any stage within 48 hours and 7 days after measurement (area under the receiver operating characteristic curve (AUC) equal to 0.70 (95%CI 0.65–0.76), AUC 0.68 (95%CI 0.63–0.73)). In the logistic regression model, 0.1 (ng/ml)2/1000-unit increment was likely to increase the risk of AKI by 2% (p = 0.002).

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“…studied a population of critically ill patients and found that the values of cell cycle arrest biomarkers were higher in transient versus persistent AKI at early hours after ICU admission. 77 Aregger et al. showed that IGFBP7 predicted mortality, renal recovery, and severity and duration of AKI in a small cohort of critically ill patients.…”

Section: Cell-cycle Arrest Biomarkers and Prognosismentioning

confidence: 99%

Clinical adoption of Nephrocheck® in the early detection of acute kidney injury

et al. 2020

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Acute kidney injury (AKI) is a common complication of acute illnesses and is associated with increased morbidity and mortality. Over the past years several AKI biomarkers for diagnostication, decision-making processes, and prognosistication of AKI and its outcomes have been developed and validated. Among these biomarkers, tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), the so-called cell cycle arrest biomarkers, showed a superior profile of accuracy and stability even in patients with substantial comorbidities. Therefore, in 2014, the US Food and Drug Administration approved the use of the product of TIMP-2 and IGFBP7 ([TIMP-2]x[IGFBP7]), known as cell cycle arrest biomarkers, to aid critical care physicians and nephrologists in the early prediction of AKI in the critical care setting. To date, NephrocheckÂ® is the only commercially available test for [TIMP-2]x[IGFBP7]. In this narrative review, we describe the growing clinical and investigational momentum of biomarkers, focusing on [TIMP-2]x[IGFBP7], as one of the most promising candidate biomarkers. Additionally, we review the current state of clinical implementation of NephrocheckÂ®.

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Predicting Acute Kidney Injury in Intensive Care Unit Patients: The Role of Tissue Inhibitor of Metalloproteinases-2 and Insulin-Like Growth Factor-Binding Protein-7 Biomarkers

Cited by 29 publications

References 30 publications

Development and validation of quick Acute Kidney Injury-score (q-AKI) to predict acute kidney injury at admission to a multidisciplinary intensive care unit

Development and validation of quick Acute Kidney Injury-score (q-AKI) to predict acute kidney injury at admission to a multidisciplinary intensive care unit

Routine Adoption of Urinary [IGFBP7]∙[TIMP-2] to Assess Acute Kidney Injury at Any Stage 12 hours After Intensive Care Unit Admission: a Prospective Cohort Study

Clinical adoption of Nephrocheck® in the early detection of acute kidney injury

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