Die neuen Player in der Pathogenese chronischer Nierenerkrankungen – FGF-23 und Klotho

Der sogenannte „fibroblast growth factor 23“, kurz FGF-23, ist ein zentraler Regulator der Kalzium-Phosphat-Homöostase, da das Hormon zum einen die renale Phosphatexkretion fördert und zum anderen durch die Hemmung der Calcitriolsynthese die intestinale Phosphataufnahme vermindert. In klinischen Studien erwiesen sich erhöhte FGF-23-Spiegel als unabhängiger Prädiktor des kardiovaskulären, des renalen und des Gesamtüberlebens chronisch nierenkranker Menschen. Rezente experimentelle Arbeiten suggerieren einen direkten kardiotoxischen Effekt von FGF-23. Der FGF-23-Korezeptor Klotho wiederum wird als membranständiges Protein in physiologischen Zielorganen von FGF-23 exprimiert. Darüber hinaus existiert eine lösliche Form von Klotho (sKlotho), der eigenständige vaskulo- und renoprotektive Eigenschaften zugesprochen werden. Die potenzielle Eignung von FGF-23 und Klotho als mögliche neue Therapieziele zur Behandlung der „chronic kidney disease – mineral bone disorder“ (CKD-MBD) ist Gegenstand aktueller klinischer und experimenteller Studien.

Fibroblast growth factor 23 (FGF-23) is a central regulator of calcium phosphate homeostasis by increasing renal phosphate excretion and decreasing gastrointestinal phosphate absorption via inhibition of calcitriol synthesis. In clinical trials, elevated FGF-23 levels were associated with impaired cardiovascular, renal and total survival in chronic kidney disease patients. Recent experimental data suggest a direct cardiotoxic effect of FGF-23. The FGF-23 co-receptor Klotho is expressed as a membrane standing form in physiological target organs of FGF-23. Additionally, a soluble form of sKlotho exists, which is thought to exert vasculo- and renoprotective functions. The meaning of FGF-23 and Klotho as potential therapeutic targets in the treatment of Chronic Kidney Disease – Mineral and Bone Disorder remains to be defined in clinical and experimental studies.

Key words

calcium - phosphate - chronic kidney disease (CKD) - FGF-23 - Klotho

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