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      Increase of urinary TIMP-2 and IGFBP7 as potential predictor of acute kidney injury requiring renal replacement therapy and patients’ outcome following complex endovascular and open thoracic abdominal aortic aneurysm surgery – a prospective observational study : A prospective observational study

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          Abstract

          Summary: Background: Acute kidney injury (AKI) as complication after open and endovascular repair of thoracoabdominal aortic aneurysm (TAAA) is one major predictor of mortality and postoperative complications. We evaluated tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) as combined early biomarker for AKI detection and predictor of patients’ outcome. Patients and methods: Between 2014 and 2015, 52 patients have been enrolled in this observational study, of whom 29 (55.8%) underwent elective open repair and 23 (44.2%) endovascular repair. TIMP2 × IGFBP7 were measured until 48 hours after admission on intensive-care unit (ICU) and were analyzed regarding their predictive ability for AKI (defined according to the KDIGO criteria) requiring temporary renal replacement therapy (RRT) and 90-day mortality using ROC curves. Results: Mean patient age was 64.5 years (Min: 43, Max: 85), endovascular treated patients were older ( p <0.0001). 40.4% ( n = 21) developed AKI, and 21.2% ( n = 11) required renal replacement therapy. In-hospital and total mortality rates were 7.7% ( n = 4) and 9.6% ( n = 5), respectively. At no time a significant difference in TIMP2 × IGFB7 levels between patients undergoing open or endovascular surgery was observed. The predictive quality of the TIMP2 × IGFBP7 value on ICU admission was sound regarding AKI requiring temporary renal replacement therapy (sensitivity: 55.56% [38.1–72.1%], specificity: 90.91% [58.7–99.8%] with an area under the curve [AUC]: 0.694 [0.543–0.820]). Mean follow-up was 13.2 months (Min: 2, Max: 20), regarding the 90-day mortality, the predictive property of the TIMP2 × IGFBP7 value was not sufficient (sensitivity: 80% [28.4–99.5%], specificity: 52.38% [36.4–68%], and AUC: 0.607 [0.454–0.746]). Conclusions: TIMP2 × IGFBP7 level measured 6–12 hrs postoperatively may be useful as an early detectable biomarker for AKI requiring temporary renal replacement therapy. It seems not suited to predict patients’ outcome following complex thoracoabdominal aortic surgery, regardless if performed by open or endovascular repair.

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          KDIGO Clinical Practice Guidelines for Acute Kidney Injury

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            Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

            Introduction Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Methods Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. Results The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. Conclusion We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.
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              Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury

              Introduction Acute kidney injury (AKI) can evolve quickly and clinical measures of function often fail to detect AKI at a time when interventions are likely to provide benefit. Identifying early markers of kidney damage has been difficult due to the complex nature of human AKI, in which multiple etiologies exist. The objective of this study was to identify and validate novel biomarkers of AKI. Methods We performed two multicenter observational studies in critically ill patients at risk for AKI - discovery and validation. The top two markers from discovery were validated in a second study (Sapphire) and compared to a number of previously described biomarkers. In the discovery phase, we enrolled 522 adults in three distinct cohorts including patients with sepsis, shock, major surgery, and trauma and examined over 300 markers. In the Sapphire validation study, we enrolled 744 adult subjects with critical illness and without evidence of AKI at enrollment; the final analysis cohort was a heterogeneous sample of 728 critically ill patients. The primary endpoint was moderate to severe AKI (KDIGO stage 2 to 3) within 12 hours of sample collection. Results Moderate to severe AKI occurred in 14% of Sapphire subjects. The two top biomarkers from discovery were validated. Urine insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2), both inducers of G1 cell cycle arrest, a key mechanism implicated in AKI, together demonstrated an AUC of 0.80 (0.76 and 0.79 alone). Urine [TIMP-2]·[IGFBP7] was significantly superior to all previously described markers of AKI (P 0.72. Furthermore, [TIMP-2]·[IGFBP7] significantly improved risk stratification when added to a nine-variable clinical model when analyzed using Cox proportional hazards model, generalized estimating equation, integrated discrimination improvement or net reclassification improvement. Finally, in sensitivity analyses [TIMP-2]·[IGFBP7] remained significant and superior to all other markers regardless of changes in reference creatinine method. Conclusions Two novel markers for AKI have been identified and validated in independent multicenter cohorts. Both markers are superior to existing markers, provide additional information over clinical variables and add mechanistic insight into AKI. Trial registration ClinicalTrials.gov number NCT01209169.
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                Author and article information

                Contributors
                Journal
                vas
                VASA
                European Journal of Vascular Medicine
                Hogrefe AG, Bern
                0301-1526
                1664-2872
                August 20, 2020
                : 50
                : 2
                : 101-109
                Affiliations
                [ 1 ]European Vascular Center Aachen-Maastricht, University Hospital Aachen, RWTH Aachen University, Germany
                [ 2 ]Department of Medical Statistics, University Hospital Aachen, RWTH Aachen University, Germany
                [ 3 ]Department of Intensive Care and Intermediate Care, University Hospital Aachen, RWTH Aachen University, Germany
                [ 4 ]Department of Anesthesiology, University Hospital Aachen, RWTH Aachen University, Germany
                Author notes
                Dr. med. Alexander Gombert PD, European Vascular Center Aachen-Maastricht, Department of Vascular Surgery, University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany, E-mail agombert@ 123456ukaachen.de
                Author information
                https://orcid.org/0000-0002-8451-2913
                Article
                vas_50_2_101
                10.1024/0301-1526/a000902
                8204b9cf-5bc0-4fca-b47c-8e260bfd51bd
                Copyright @ 2020
                History
                : May 28, 2020
                : July 29, 2020
                Categories
                Original communication

                Medicine
                intensive care unit,IGFBP7,AKI,TIMP-2,biomarker,TAAA-repair
                Medicine
                intensive care unit, IGFBP7, AKI, TIMP-2, biomarker, TAAA-repair

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