Perioperative Untersuchungen der Urinkonzentrationen von TIMP-2 und IGFBP7 als prädiktive Biomarker für akute Nierenschädigungen nach kardiochirurgischen Operationen an der Herz-Lungen-Maschine

Die akute Nierenschädigung (ANS) ist eine häufige Komplikation im Rahmen kardiochirurgischer Operationen an der Herz-Lungen-Maschine mit einer deutlichen Verschlechterung der Prognose. In dieser Studie wurden die Konzentrationen der Proteine TIMP-2 (tissue inhibitor of metalloproteinases-2) und IGFB...

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Bibliographic Details
Main Author: Beckers, Julius
Contributors: Vogt, Sebastian (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2019
Online Access:PDF Full Text
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Table of Contents: Acute kidney injury (AKI) is a frequent complication associated with on-pump cardiac surgery with a considerable deterioration of the prognosis. The urinary concentrations of TIMP-2 (tissue inhibitor of metalloproteinases-2) und IGFBP7 (insulin-like growth factor binding protein) as predictors for AKI were studied. Fifty patients for on-pump cardiac surgery were enrolled in the study. Urinary samples were taken preoperatively, intraoperatively at 30 and 60 minutes after aortic clamping and 0 ,6 ,12 and 24 hours after admission to the intensive care unit (ICU), respectively. The parameters were examined using the NephroCheck® Testkit and calculated as a product of [TIMP-2] and [IGFBP7]. Additionally, urinary dilution parameters like osmolality, urea, uric acid and creatinine were measured. The primary endpoint – AKI – was defined by KDIGO-Guidelines using serum creatinine concentrations and weight-adjusted urine production per hour. 28 percent of the patients developed AKI at KDIGO stage 1. Significant subgroup differences for [TIMP-2] × [IGFBP7] were shown at 0 and 24 hours after admission to ICU. This study addressed the efficient cut-off levels for early detection of AKI. The cut-off at 0 hours was amounted to 0,07 with a sensitivity of 84,6% and a specificity of 55,6%. At 24 hours this cut-off was 0,35 with a sensitivity of 53,8% and a specificity of 88,2%. The corresponding receiver operating characteristic (ROC) curves demonstrated areas under the curve (AUC) of 0,725 and 0,718. Suggested cut-offs at 0,3 and 2,0 could not be confirmed. For ([TIMP-2] × [IGFBP7] )/osmolality ideal cut-offs showed sensitivities and specificities of 81,8% and 66,7% at 0 hours and of 83,3% and 73,5% at 24 hours. The AUCs of the ROC-curves amounted to 0,739 and 0,767, respectively. Serum creatinine reached its peak 48 hours after admission to ICU. [TIMP-2]× [IGFBP7] is suitable for postoperative risk assessment of AKI, although previous cut-off data could not be confirmed. Correlation with urinary dilution – as suggested in ([TIMP-2] × [IGFBP7] )/Osmolalität – may simplify the identification of universal cut-offs.