Calcium Deficiency Reduces Circulating Levels of FGF23 : Journal of the American Society of Nephrology (original) (raw)

Basic Research

Rodriguez-Ortiz, María E.*; Lopez, Ignacio†; Muñoz-Castañeda, Juan R.*; Martinez-Moreno, Julio M.*; Ramírez, Alan Peralta‡; Pineda, Carmen†; Canalejo, Antonio§; Jaeger, Philippe‖; Aguilera-Tejero, Escolastico†; Rodriguez, Mariano¶; Felsenfeld, Arnold**; Almaden, Yolanda*

*Research Unit, IMIBIC, Hospital Universitario Reina Sofia, Cordoba, Spain;

†Department of Medicina y Cirugia Animal, Universidad de Cordoba, Cordoba, Spain;

‡Escuela de Medicina Veterinaria, UNAN-León, Nicaragua and Fundación Carolina, Spain;

§Department of Biologia Ambiental y Salud Publica, Universidad de Huelva, Huelva, Spain;

‖Centre for Nephrology, University College of London, London, United Kingdom;

¶Servicio de Nefrologia, Red in Ren, IMIBIC, Hospital Universitario Reina Sofia, Cordoba, Spain; and

**Department of Medicine, Veterans Affairs Greater Los Angeles Healthcare System and the David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California

Correspondence: Dr. Mariano Rodriguez, Unidad de Investigación, Hospital Universitario Reina Sofia, Avda Menendez Pidal s/n, Cordoba 14004, Spain. Email: [email protected]

Received October 20, 2011

Accepted March 30, 2012

Abstract

Fibroblast growth factor (FGF) 23 inhibits calcitriol production, which could exacerbate calcium deficiency or hypocalcemia unless calcium itself modulates FGF23 in this setting. In Wistar rats with normal renal function fed a diet low in both calcium and vitamin D, the resulting hypocalcemia was associated with low FGF23 despite high parathyroid hormone (PTH) and high calcitriol levels. FGF23 correlated positively with calcium and negatively with PTH. Addition of high dietary phosphorus to this diet increased FGF23 except in rats with hypocalcemia despite high PTH levels. In parathyroidectomized rats, an increase in dietary calcium for 10 days increased serum calcium, with an associated increase in FGF23, decrease in calcitriol, and no change in phosphorus. Also in parathyroidectomized rats, FGF23 increased significantly 6 hours after administration of calcium gluconate. Taken together, these results suggest that hypocalcemia reduces the circulating concentrations of FGF23. This decrease in FGF23 could be a response to avoid a subsequent reduction in calcitriol, which could exacerbate hypocalcemia.