Pathogenese des renalen sekundären Hyperparathyreoidismus

H. Reichel

doi:10.1055/s-0037-1619856

Osteologie, Inhaltsverzeichnis

Osteologie 2008; 17(03): 113-118
DOI: 10.1055/s-0037-1619856

Renale Osteopathie

Schattauer GmbH

Pathogenese des renalen sekundären Hyperparathyreoidismus

Pathogenesis of renal secondary hyperparathyroidism

H. Reichel

¹Nephrologisches Zentrum, Villingen-Schwenningen

› Institutsangaben

Abstract

Zusammenfassung

Ein renaler sekundärer Hyperparathyreoidismus (sHPT) wird bei der Mehrzahl der Patienten mit chronischer Nierenerkrankung diagnostiziert. Neben ossären Beschwerden ist der ausgeprägte sHPT mit extraossären klinischen Komplikationen wie erhöhter kardiovaskulärer Morbidität und Mortalität assoziiert. Die Pathogenese des renalen sHPT ist komplex und umfasst mehrere Faktoren. Der Mangel des renal synthetisierten aktiven Vitamin-D-Hormons Calcitriol führt zu gesteigerter PTH-Synthese und Förderung der Parathyreoidea-Proliferation (d. h. Vergrößerung des Pools PTH-sezernierender Zellen). Durch direkte Effekte auf die Parathyreoideae und indirekte Effekte ist die Hyperphosphatämie durch Steigerung der PTH-Synthese und Parathyreoidea-Proliferation maßgeblich an der Entwicklung des sHPT beteiligt. Hypokalzämie und verminderte Aktivierung des Kalzium-Sensing-Rezeptors (CaR) resultieren in verminderter Kalziumsensitivität der Parathyreoideae, gesteigerter PTH-Synthese und gesteigerter Parathyreoidea-Proliferation. Eine mit zunehmender Dauer der Urämie progrediente noduläre Parathyreoidea-Hyperplasie begünstigt die Entwicklung eines autonomen HPT. Bei nodulärer Hyperplasie sind der Vitamin-D-Rezeptorbestand und der CaR-Bestand der Parathyreoideazelle vermindert; häufiger bestehen chromosomale Veränderungen, die monoklonales Wachstum induzieren. Weitere Faktoren, die an der Pathogenese des sHPT beteiligt sind, umfassen skelettäre PTH-Resistenz, Mangel an nativem Vitamin D, metabolische Azidose und möglicherweise ein Anstieg von zirkulierendem FGF-23.

Summary

The majority of patients with chronic renal disease will develop renal secondary hyperparathyroidism (sHPT). Pronounced sHPT is associated, besides osseous symptoms, with extraosseous complications, namely increased cardiovascular morbidity and mortality. Pathogenesis of renal sHPT is complex. Reduced renal synthesis of the active vitamin D hormone calcitriol results in increased PTH-synthesis and parathyroid proliferation (i. e. an increase in the pool of PTH-secreting cells). Hyperphosphatemia stimulates PTH-synthesis and parathyroid proliferation through direct effects on the parathyroids and through indirect effects. Hypocalcemia and reduced activation of the parathyroid calcium-sensing receptor (CaR) cause decreased calcium-sensitivity of parathyroid glands, enhanced PTH-synthesis and parathyroid proliferation. Nodular parathyroid hyperplasia which occurs more frequently with increasing duration of uremia favors development of autonomous HPT. Nodular hyperplasia is associated with reduced vitamin D receptor and CaR expression and with chromosomal alterations which favor monoclonal growth. Additional factors which are involved in pathogenesis of sHPT comprise skeletal PTH-resistance, deficiency of native vitamin D, metabolic acidosis and possibly increased circulating FGF-23.

Schlüsselwörter

Renaler sekundärer Hyperparathyreoidismus - Calcitriol - Parathormon - Hyperphosphatämie - Hypokalzämie

Keywords

Renal secondary hyperparathyroidism - calcitriol - parathyroid hormone - hyperphosphatemia - hypocalcemia

Volltext

Referenzen

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