Urinary [TIMP-2]·[IGFBP7]-guided randomized controlled intervention trial to prevent acute kidney injury in the emergency department

Schanz, Moritz; Wasser, Christoph; Allgaeuer, Sebastian; Schricker, Severin; Dippon, Juergen; Alscher, Mark Dominik; Kimmel, Martin

doi:10.1093/ndt/gfy186

Cited by 32 publications

(42 citation statements)

References 22 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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“…Like procalcitonin in sepsis, the role of [TIMP-2]∙[IGFBP7] is to guide the clinician in a timely manner for further intervention of the patients at risk. While the time window for intervention or the algorithm of therapy have been well identified for other acute conditions with high morbidity and mortality, no such timeframe or specific therapy has been definitively clarified for AKI, even if some previous studies have identified a time window for intervention for AKI 26,27 . The UK National Health Service found that delayed identification of patients with AKI contributes to worsening outcomes 28 .…”

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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“…[TIMP-2]Â[IGFBP7] was also shown to be a predictor of AKI in many other settings like decompensated heart failure, 60 cardiac arrest, [61][62][63] emergency department 64 and sepsis. [65][66][67] There are also some other investigations in post-chemotherapy toxicity, 68,69 and obstetric-related critical illness, 70,71 which shows cell cycle arrest biomarkers' performance to be suboptimal.…”

Section: Risk and Development Of Akimentioning

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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Urinary [TIMP-2]·[IGFBP7]-guided randomized controlled intervention trial to prevent acute kidney injury in the emergency department

Abstract: www.ClinicalTrials.gov, study number NCT02730637.

Cited by 32 publications

References 22 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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