Impact of phosphorus restriction and vitamin D-substitution on secondary hyperparathyroidism in a proteinuric mouse model.

Abstract

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, SHPT was mild (PTH increase 2.4-fold), and serum levels of FGF23, phosphate and urea remained almost stable, whereas mice with heavy 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 (Pi 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.

• Authors: Bernhard N Bohnert, Christoph Daniel, Kerstin Amann, Jakob Voelkl, Ioana Alesutan, Florian Lang, Nils Heyne, Hans-Ulrich Häring, Ferruh Artunc
• Journal: Kidney & blood pressure research (Kidney Blood Press Res) Vol. 40 Issue 2 Pg. 153-65 ( 2015) ISSN: 1423-0143 [Electronic] Switzerland
• PMID: 25871296 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• Fgf23 protein, mouse
• Vitamins
• Vitamin D
• Phosphorus
• Fibroblast Growth Factor-23
• Doxorubicin
• Cyp24a1 protein, mouse
• Vitamin D3 24-Hydroxylase
• Glucuronidase
• Klotho Proteins

Topics

• Animals
• Doxorubicin
• Fibroblast Growth Factor-23
• Glucuronidase (biosynthesis, genetics)
• Hyperparathyroidism, Secondary (chemically induced, diet therapy, drug therapy)
• Kidney (pathology)
• Klotho Proteins
• Mice
• Phosphorus
• Proteinuria (chemically induced, diet therapy, etiology)
• Renal Insufficiency (prevention & control)
• Vitamin D (therapeutic use)
• Vitamin D3 24-Hydroxylase (biosynthesis, genetics)
• Vitamins (therapeutic use)