Phosphatregulation und kardiovaskuläre Konsequenzen – Was ist bei chronisch nierenerkrankten Patienten zu beachten?

Chronisch nierenerkrankte Patienten leiden häufig unter einer Störung des Phosphathaushaltes. Mit zunehmendem Funktionsverlust der Niere kommt es zu einer Phosphatretention und einem progredienten Anstieg des Fibroblasten-Wachstums-Faktor-23 (FGF-23), einem Hormon, das den Serum-Phosphat-Haushalt reguliert. Erhöhte Serum-Phosphat- und FGF-23-Spiegel sind mit einem erhöhten Risiko für die Gesamtsterblichkeit und dem Auftreten kardiovaskulärer Ereignisse assoziiert. Interessanterweise besteht eine vom Phosphatspiegel unabhängige Assoziation zwischen erhöhten FGF-23-Spiegeln und kardiovaskulärer Morbidität und Mortalität. Besonders ausgeprägt ist die Assoziation zwischen erhöhten FGF-23-Spiegeln und Herzinsuffizienz. Basierend auf diesen Beobachtungen lässt sich vermuten, dass erhöhte Serum-Phosphat- und FGF-23-Spiegel unabhängig voneinander das kardiovaskuläre Risiko beeinflussen können. Tatsächlich konnte in tierexperimentellen Studien gezeigt werden, dass erhöhte Serum-Phosphat-Spiegel über eine frühzeitige Endothelschädigung und eine akzelerierte vaskuläre Kalzifikation gefäßschädigend wirken. Erhöhte FGF-23-Spiegel hingegen scheinen primär die Entwicklung einer linksventrikulären Hypertrophie zu triggern. Aufgrund dieser potenziell unterschiedlichen Schädigungsmuster sollten zukünftige Behandlungskonzepte möglichst beide Serumfaktoren senken, um das hohe kardiovaskuläre Risiko nierenerkrankter Patienten zu reduzieren.

Hyperphosphatemia is a hallmark of renal disease. When chronic kidney disease progresses, decreasing kidney function leads to phosphate retention and an increase in serum levels of fibroblast growth factor 23 (FGF-23). FGF-23 is an endocrine hormone that regulates phosphate metabolism. In renal patients, high levels of serum phosphate and FGF-23 are associated with an increased risk of cardiovascular events and mortality. Interestingly, recent studies have noted phosphate-independent associations between higher FGF-23 levels and cardiovascular morbidity and mortality. In these studies, FGF-23 was strongly associated with myocardial hypertrophy and failure events. On the other hand, higher serum phosphate levels are also associated with cardiovascular risk independently of FGF-23 levels in patients with and without kidney disease. Considering these observations, one can assume that serum phosphate and FGF-23 may function independently from each other to affect the cardiovascular system. Animal studies could demonstrate that increasing phosphate concentrations lead to endothelial dysfunction and progressive vascular calcification, while high FGF-23 levels seem to trigger the development of heart hypertrophy. Because of these potentially distinct mechanisms of cardiovascular damage, future therapeutic interventions should target both serum factors simultaneously to further reduce the cardiovascular burden among these high-risk patients.

Key words

chronic kidney disease - hyperphosphatemia - fibroblast growth factor 23 - endothelial dysfunction - vascular calcification - heart hypertrophy

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