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Was gibt es Neues in der CKD-MBD-Pathogenese?

What’s new in CKD-MBD pathogenesis?

  • Leitthema
  • Published:
Der Nephrologe Aims and scope

Zusammenfassung

In den letzten Jahren wurde unser pathophysiologisches Verständnis des Kalzium-Phosphat-Haushalts durch die Entdeckung von Klotho und FGF-23 revolutioniert: In Anwesenheit des Korezeptors Klotho bindet FGF-23 an den FGF-Rezeptor auf renalen Zielzellen und bewirkt eine vermehrte renale Phosphatausscheidung sowie eine verminderte Bildung von Calcitriol, wodurch eine negative Phosphatbilanz resultiert. Trotz dieser vermeintlich protektiven Eigenschaft waren in zahlreichen Kohortenstudien erhöhte FGF-23-Plasmaspiegel prädiktiv für kardiovaskuläre Ereignisse und Todesfälle. In Einklang wurde in experimentellen Arbeiten eine direkte, Klotho-unabhängige myokardtoxische Wirkung von FGF-23 beschrieben. Neben der membranständigen Form von Klotho, die als Korezeptor von FGF-23 dient, existiert eine lösliche Form von Klotho (sKlotho). sKlotho wurde mit parakrinen und endokrinen protektiven Effekten assoziiert, deren genaue biologische Bedeutung allerdings noch inkomplett verstanden ist, allerdings zumindest experimentell den Effekten von FGF-23 ähnelt.

Abstract

Knowledge on the pathophysiology of calcium phosphate metabolism has recently been revolutionized by the discovery of Klotho and fibroblast growth factor (FGF) 23. In the presence of its co-receptor Klotho, FGF-23 binds to receptors on renal cells resulting in an increased renal phosphate excretion and reduced synthesis of calcitriol leading subsequently to a negative phosphate balance. Despite these seemingly protective effects, numerous cohort studies identified elevated FGF-23 as a strong predictor of increased cardiovascular morbidity and mortality. In line with these findings experimental studies recently revealed a direct Klotho-independent toxic effect of FGF-23 on myocardial cells. In addition to the membrane bound form, which serves as the FGF-23 co-receptor, a secreted soluble variant (sKlotho) was recently discovered which has been associated with paracrine and endocrine protective functions. Although the biological relevance of sKlotho remains to be elucidated its effects are at least experimentally similar to those of FGF-23.

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Interessenkonflikt

Die korrespondierende Autorin weist auf folgende Beziehungen hin: GHH hat Vortragshonrare von der Fa. Shire erhalten. DF hat Vortrags- und Beraterhonorare von Amgen, Abbott, Sanofi-enzyme, Shire und FMC erhalten. SS: kein Interessenkonflikt.

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  1. Klinik für Innere Medizin IV – Nieren- und Hochdruckkrankheiten, Universitätsklinikum des Saarlandes, Homburg/Saar, Deutschland

    S. Seiler, G.H. Heine & D. Fliser

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  1. S. Seiler
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  2. G.H. Heine
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  3. D. Fliser
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Correspondence to S. Seiler.

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Seiler, S., Heine, G. & Fliser, D. Was gibt es Neues in der CKD-MBD-Pathogenese?. Nephrologe 8, 13–20 (2013). https://doi.org/10.1007/s11560-012-0646-7

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