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.
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: Daniel Essigke; Bernhard N Bohnert; Andrea Janessa; Matthias Wörn; Kingsley Omage; Hubert Kalbacher; Andreas L Birkenfeld; Thomas H Bugge; Roman Szabo; Ferruh Artunc Journal: Pflugers Arch Date: 2022-03-21 Impact factor: 4.458
Authors: Ferruh Artunc; Bernhard N Bohnert; Jonas C Schneider; Tobias Staudner; Florian Sure; Alexandr V Ilyaskin; Matthias Wörn; Daniel Essigke; Andrea Janessa; Nis V Nielsen; Andreas L Birkenfeld; Michael Etscheid; Silke Haerteis; Christoph Korbmacher; Sandip M Kanse Journal: Pflugers Arch Date: 2021-12-06 Impact factor: 4.458
Authors: Bernhard N Bohnert; Irene Gonzalez-Menendez; Thomas Dörffel; Jonas C Schneider; Mengyun Xiao; Andrea Janessa; M Zaher Kalo; Birgit Fehrenbacher; Martin Schaller; Nicolas Casadei; Kerstin Amann; Christoph Daniel; Andreas L Birkenfeld; Florian Grahammer; Lahoucine Izem; Edward F Plow; Leticia Quintanilla-Martinez; Ferruh Artunc Journal: Dis Model Mech Date: 2021-09-15 Impact factor: 5.758