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Die Rolle der Thrombozyten bei Atherosklerose, Diabetes mellitus und chronischer Niereninsuffizienz

Ein Versuch, die Resultate der TREAT-Studie zu erklären

The Role of Platelets in Atherosclerosis, Diabetes Mellitus, and Chronic Kidney Disease. An Attempt at Explaining the TREAT Study Results

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Zusammenfassung

Erythropoesestimulierende Arzneimittel (ESA) werden zur Behandlung der renalen Anämie eingesetzt. Nachdem bei der TREAT-Studie (Trial to Reduce Cardiovascular Events with Aranesp Therapy) mit niereninsuffizienten Diabetikern die Apoplexinzidenz in der ESA-Gruppe signifikant höher war als in der Kontrollgruppe, stellt sich die Frage nach der Ursache für dieses Phänomen. Eine entscheidende Rolle dürfte hierbei den Blutplättchen zukommen. Bei der Atherogenese spielen sich komplexe Interaktionen zwischen Plättchen und Monozyten (Plättchen/Monozyten-„Crosstalk“) sowie Endothel ab. Hierbei sind insbesondere bei Diabetes mellitus die Plättchen aktiviert. Bei der Atherogenese sind andere Plättchenpartialfunktionen von Relevanz als jene, die der Cyclooxygenaseinhibitor Acetylsalicylsäure und Antagonisten des Adenosindiphosphatrezeptors P2Y12wie die Thienopyridine hemmen. Stattdessen sind für den Plättchen/Monozyten-„Crosstalk“ Adhäsionsrezeptoren wie Selectine und Integrine von Bedeutung. Zusätzlich bewirken ESA direkt und indirekt eine Plättchenaktivierung. Antagonistisch besteht hierzu bei schwerer chronischer Niereninsuffizienz infolge Thrombozytopathie eine renale Blutungsneigung, die durch adäquate Nierenersatztherapie und ESA-Gabe mit Erreichen eines Hämoglobins (Hb) von 10 g/dl beseitigt werden kann. Wird jedoch ein Hb von 10 g/dl überschritten, führt die noch stärkere ESA-bedingte Plättchenaktivierung zusammen mit der diabetisch verursachten zu einer prothrombotischen Situation, die bei Patienten mit ausgepägter Atherosklerose in akuten atherothrombotischen Komplikationen resultieren kann, für deren Zustandekommen die Plättchen von zentraler Bedeutung sind. Dies wäre eine Hypothese zur Erklärung für die erhöhte Apoplexinzidenz im Rahmen der TREAT-Studie.

Abstract

Erythropoiesis-stimulating agents (ESA) are used to treat renal anemia. The TREAT study (Trial to Reduce Cardiovascular Events with Aranesp Ther- apy) of diabetic patients with chronic kidney disease (CKD) found that the risk of stroke was significantly higher than in the control arm. This raises the question as to what causes this phenomenon. Platelets may play a crucial role in this context. Atherogenesis involves complex interactions between platelets and monocytes (platelet-monocyte crosstalk) and with endothelial cells. Platelets are activated in cases of diabetes mellitus, especially. During atherogenesis, partial functions of platelets other than those inhibited by aspirin, as a cyclooxygenase inhibitor, or by adenosine diphosphate receptor P2Y12antagonists, such as thienopyridines, are of relevance. During platelet-monocyte crosstalk, specifically, an important role is played by adhesion receptors such as selectins and integrins. In addition, ESA cause platelet activation by direct and indirect mechanisms. Antagonistic thereto is a renal bleeding tendency in cases of severe CKD, due to platelet dysfunction, which can be remedied with appropriate renal replacement therapy and administration of ESA in order to reach a hemoglobin (Hb) level of 10 g/dl. However, if the Hb level exceeds 10 g/dl, the even stronger platelet activation caused by ESA, combined with the activation caused by diabetes, leads to a prothrombotic state, which in patients with severe atherosclerosis can result in acute atherothrombotic complications, in the genesis of which platelets play a key role. This would be one hypothesis for explaining the increased incidence of strokes in the TREAT study.

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  1. KfH-Nierenzentrum, Neuwied, Germany

    Norbert Maurin

  2. Internist/Nephrologie, Intensivmedizin KfH-Nierenzentrum Neuwied Engerser, Landstraße 78, 56564, Neuwied, Germany

    Norbert Maurin

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Maurin, N. Die Rolle der Thrombozyten bei Atherosklerose, Diabetes mellitus und chronischer Niereninsuffizienz. Med Klin 105, 339–344 (2010). https://doi.org/10.1007/s00063-010-1062-2

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