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„Tissue inhibitor of metalloproteinase 2“ und „insulin-like growth factor-binding protein 7“

Neue Biomarkerkombination zur Früherkennung der akuten Nierenschädigung in der Herzchirurgie

Tissue inhibitor of metalloproteinase 2 and insulin-like growth factor-binding protein 7

New biomarker combination for early recognition of acute kidney injury in cardiac surgery

  • Perioperative Medizin
  • Published:
Zeitschrift für Herz-,Thorax- und Gefäßchirurgie Aims and scope

Zusammenfassung

Die akute Nierenschädigung („acute kidney injury“, AKI) tritt mit einer Inzidenz bis zu 30 % nach kardiochirurgischen Eingriffen auf, bei etwa 1 % der Patienten als dialysepflichtiges Nierenversagen, weshalb der Begriff „cardiac surgery-associated acute kidney injury“ (CSA-AKI) geprägt wurde. Die AKI-assoziierte Mortalität beträgt zwischen 15 % und 30 %, und eine CSA-AKI erhöht die Mortalität, unabhängig von der Komorbidität. Patienten mit AKI sollten schnell identifiziert werden, um früh prophylaktische oder therapeutische Interventionen einzuleiten und eine weitere Nierenschädigung zu vermeiden. Serum-Kreatinin-Konzentration und Diurese als Goldstandard in der Diagnose und der Definition der AKI sind für diese frühe Identifikation nicht geeignet. Auch viele neue Biomarker, wie Neutrophilengelatinase-assoziiertes Lipocalin (NGAL) oder Cystatin C haben sich nach initial vielversprechenden Studienergebnissen nicht in der klinischen Routine durchsetzen können. In mehreren multizentrischen Studien zeigten sich „insulin-like growth factor-binding protein 7“ (IGFBP7) und „tissue inhibitor of metalloproteinase 2“ (TIMP2) als Induktoren eines Zellzyklusarrests allen anderen der 340 untersuchten Biomarker im Hinblick auf die Vorhersage einer AKI überlegen. Auch rein kardiochirurgische Arbeiten bestätigen die hohe Sensitivität und Spezifität in der Früherkennung einer drohenden AKI. Erste prospektiv-randomisierte Studien belegen, dass die frühe Erkennung des AKI und die zeitgerechte Einleitung präventiver oder therapeutischer Interventionen, basierend auf diesen vielversprechenden Biomarkern, die Progression des AKI senken können.

Abstract

Acute kidney injury (AKI) occurs in up to 30% of patients after cardiac surgery and in approximately 1% results in kidney failure necessitating dialysis. This has given rise to the term cardiac surgery-associated AKI (CSA-AKI). The mortality associated with AKI is 15–30% and CSA-AKI increases the mortality independent of comorbidities. Patients with AKI must be rapidly identified in order to initiate prophylactic or therapeutic interventions at an early stage and avoid further renal damage. Serum creatinine concentrations and diuresis, which are the gold standard in the diagnosis and definition of AKI, are not suitable for this early recognition. Following very promising results of initial studies many new biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C have not become established in the clinical routine. In many multicentric studies insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinase 2 (TIMP2), which are inductors of cell cycle arrest, were found to be superior to all of the other 340 biomarkers investigated with respect to prediction of AKI. Even studies purely involving cardiothoracic surgery confirmed the high sensitivity and specificity in the early recognition of impending AKI. A recently published randomized trial showed that early recognition of AKI and timely initiation of preventive or therapeutic interventions based on these promising biomarkers, can inhibit the progression of AKI.

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Authors and Affiliations

  1. Klinik für Intensivmedizin, Imland Klinik Rendsburg, Lilienstr. 22–28, 24768, Rendsburg, Deutschland

    K. Pilarczyk & N. Haake

  2. Klinik für Herz- und Gefäßchirurgie, Universitätsklinikum Schleswig-Holstein, Campus Kiel, Kiel, Deutschland

    B. Panholzer, A. Haneya & J. Cremer

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Correspondence to K. Pilarczyk.

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Interessenkonflikt

Die Fa. Astute Medical hat wissenschaftliche Arbeiten zum Einsatz von TIMP2 und IGFBP7 als neuer Biomarker zur Früherkennung der AKI in der Herzchirurgie von K. Pilarczyk, B. Panholzer, A. Haneya und J. Cremer finanziell unterstützt. N. Haake gibt an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Pilarczyk, K., Panholzer, B., Haneya, A. et al. „Tissue inhibitor of metalloproteinase 2“ und „insulin-like growth factor-binding protein 7“. Z Herz- Thorax- Gefäßchir 31, 190–199 (2017). https://doi.org/10.1007/s00398-017-0142-5

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  • DOI: https://doi.org/10.1007/s00398-017-0142-5

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