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Vitamin D-Metabolismus bei Niereninsuffizienz — Störung eines endokrinen Regelkreises

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Zusammenfassung

In den proximalen Tubulusepithelien der Niere wird der Vitamin D-Metabolit 25(OH)D in das aktive Secosterol 1,25(OH)2D3 umgewandelt. Diese Umwandlung ist bei niereninsuffizienten Patienten beeinträchtigt, jedoch sind möglicherweise nicht alle Vitamin D-abhängigen Störungen bei Niereninsuffizienz allein durch den Ausfall der Synthese von 1,25(OH)2D3 zu erklären.

Bei initialer Niereninsuffizienz, bei der bereits Vitamin D-abhängige Funktionen (calzämische Wirkung von PTH, Calziumabsorption) gestört sind, liegen die 1,25(OH)2D3-Spiegel im Serum geringfügig oberhalb des Normalbereichs. Dieser Befund ist mit einer inadäquaten Antwort der 1-alpha-Hydroxylase auf aktivierende Stimuli (Hyperparathyreoidismus, Hypocalzämie, Hypophosphatämie) und/oder einer möglichen Endorganresistenz gegenüber 1,25(OH)2D3 vereinbar.

Die Osteomalazie bei niereninsuffizienten Patienten ist nicht ausschließlich als Folge der Erniedrigung der Serum-Konzentration eines der bekannten Vitamin D-Metabolite [25(OH)D3; 24,25(OH)2D3; 1,25(OH)2D3] zu erklären. Das schlechte Ansprechen der Osteomalazie urämischer Patienten auf 1,25(OH)2D3 legt die Frage nach der möglichen Wirkung zusätzlicher Vitamin D-Metabolite oder dem Vorhandensein nicht Vitamin D-abhängiger Zusatzfaktoren nahe. Bislang fehlen Informationen zum Verhalten der 1,25(OH)2D3 Rezeptoren und nachgeschalteter Ereignisse an Knochenzellen und Einzelheiten einer möglichen Wechselwirkung zwischen 1,25(OH)2D3 und PTH bleiben noch unklar.

Obwohl ein spezifischer wachstumsfördernder Effekt von 1,25(OH)2D3 auf das Längenwachstum urämischer Kinder beschrieben wurde, zeigten mehrere klinische und experimentelle Untersuchungen keine Normalisierung durch 1,25(OH)2D3 resp. keinen Wirkunterschied zwischen Vitamin D und 1,25(OH)2D3.

Gegenwärtig ist noch unklar, ob Vitamin D-Metabolite, und gegebenenfalls welcher Vitamin D-Metabolit, die PTH-Sekretion der Parathyreoidea hemmen. Die Klärung dieser Frage erscheint dringend für eine optimale medikamentöse Suppression der Parathyreoidea niereninsuffizienter Patienten.

Auch außerhalb der Homöostase des Ca-Pi-Stoff-wechsels spielen Vitamin D-Metabolite eine wichtige Rolle in der Funktion einiger Organe, z.B. Muskel, Hoden, Pankreas etc. Der Ausfall dieser Funktionen ist möglicherweise bedeutsam zum Verständnis des urämischen Syndroms und seiner mangelnden Rückbildung unter Hämodialysebehandlung.

Summary

The vitamin metabolite 25(OH)D is transformed into the active secosterole 1.25(OH)2D3 in the proximal tubular epithelium of the kidney. This transformation is disturbed in patients with renal insufficiency. However, this review shows that presumably not all vitamin D dependent disturbances in patients with renal insufficiency are explicable merely as the consequence of reduced renal synthesis of 1.25(OH)2D3 secondary to nephronal loss.

In incipient renal failure, vitamin D dependent functions (calcemic action of PTH, intestinal absorption of Ca) are disturbed. Yet, circulating 1.25(OH)2D3 levels are slightly elevated. This finding is compatible with an inadequate response of the renal 1-alpha-hydroxylase system to activating stimuli (hyperparathyroidism, hypocalcemia, fasting hypophosphatemia) and/or end-organ resistance to the action of 1.25(OH)2D3.

Osteomalacia in renal insufficiency cannot entirely be explained as the consequence of a reduction of the serum-concentration of any of the known vitamin D metabolites [25(OH)D3; 1.25(OH)2D3; 24.25(OH)2D3]. The relatively poor response of osteomalacia of uremic patients to the administration of 1.25(OH)2D3 leads to the question of whether other vitamin D metabolites or non-vitamin D related factors are important in its genesis. Critical information is lacking with respect to 1.25(OH)2D3 receptors, post receptor events and interaction between vitamin D metabolites and PTH in bone cells of such patients.

A specific action of 1.25(OH)2D3 on longitudinal growth of uremic children has been described. However, several clinical and experimental studies failed to provide evidence of normalization of growth by 1.25(OH)2D3 and failed to show differences in this respect between vitamin D and 1.25(OH)2D3.

Currently, it remains undecided whether vitamin D metabolites affect PTH secretion, and if so which vitamin D metabolite is involved. Clarification of this problem is of paramount importance for therapeutic suppression of the parathyroids of uremic patients.

Vitamin D metabolites play an important role in some organ functions unrelated to homeostasis of Ca-Pi-metabolism (e.g. muscle, testis, pancreas, etc). The loss of such function is of potential importance in the genesis of the uremic syndrome and its imcomplete reversal by hemodialysis.

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Abbreviations

PTH:

Parathormon

iPTH:

immunreaktives Parathormon

cAMP:

zyklisches Adenosinmonophosphat

1,25(OH)2D3 :

1,25(OH)2 Vitamin D3

Ca:

Calcium

Pi:

Phosphat

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  1. Medizinische Universitätsklinik, Bergheimer Str. 59, D-6900, Heidelberg, Bundesrepublik Deutschland

    E. Ritz, W. Kreusser, R. Boland & J. Bommer

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  1. E. Ritz
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Ritz, E., Kreusser, W., Boland, R. et al. Vitamin D-Metabolismus bei Niereninsuffizienz — Störung eines endokrinen Regelkreises. Klin Wochenschr 57, 1053–1059 (1979). https://doi.org/10.1007/BF01479991

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