Impact of Phosphorus Restriction and Vitamin D-Substitution on Secondary Hyperparathyroidism in a Proteinuric Mouse Model

Background/Aims: Since the discovery of FGF23, secondary hyperparathyroidism (SHPT) in renal disease has been considered to result primarily from phosphorus retention rather than vitamin D deficiency. However, the impact of phosphorus restriction and vitamin D supplementation on SHPT is still ill de...

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Bibliographic Details
Published in:Kidney & blood pressure research 2015-01, Vol.40 (2), p.153-165
Main Authors: Bohnert, Bernhard N., Daniel, Christoph, Amann, Kerstin, Voelkl, Jakob, Alesutan, Ioana, Lang, Florian, Heyne, Nils, Häring, Hans-Ulrich, Artunc, Ferruh
Format: Article
Language:English
Subjects:
Animals
Doxorubicin
Glucuronidase - biosynthesis
Glucuronidase - genetics
Hyperparathyroidism, Secondary - chemically induced
Hyperparathyroidism, Secondary - diet therapy
Hyperparathyroidism, Secondary - drug therapy
Kidney - pathology
Mice
Nephrotic syndrome
Original Paper
Phosphorus
Proteinuria - chemically induced
Proteinuria - diet therapy
Proteinuria - etiology
Renal Insufficiency - prevention & control
SHPT
Vitamin D - therapeutic use
Vitamin D3 24-Hydroxylase - biosynthesis
Vitamin D3 24-Hydroxylase - genetics
Vitamins - therapeutic use
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Summary:Background/Aims: Since the discovery of FGF23, secondary hyperparathyroidism (SHPT) in renal disease has been considered to result primarily from phosphorus retention rather than vitamin D deficiency. However, the impact of phosphorus restriction and vitamin D supplementation on SHPT is still ill defined. Methods: We investigated the development of SHPT in a doxorubicin-induced proteinuric mouse model and tested different treatment strategies including a low phosphorus diet and substitution with native or active vitamin D in 129 S1/SvImJ wild-type mice. Results: Development of SHPT at day 30 was strongly related to the magnitude of induced proteinuria. In mice with a proteinuria 100 mg/mg creatinine) developed marked SHPT (PTH increase 10.1-fold) accompanied by massive increase in FGF23 (27.0-fold increase), hyperphosphatemia (1.8-fold increase), renal failure (7.3-fold urea increase) and depletion of both 25-OH vitamin D and 1,25-OH vitamin D. Substitution with native or active vitamin D was unable to suppress SHPT, whereas a low-phosphorus diet (P i content 0.013%) completely suppressed SHPT in mice with both mild and heavy proteinuria. Conclusions: The development of SHPT resulted from phosphate retention in this proteinuric model and could completely be suppressed with a low-phosphorus diet.
ISSN:1420-4096
1423-0143
DOI:10.1159/000368491