title: Calcium and vitamin D have a synergistic role in a rat model of kidney stone disease.
abstract: Vitamin D supplementation in humans should be accompanied by calcium administration to avoid bone demineralization through vitamin D receptor signaling. Here we analyzed whether long-term exposure of rats to vitamin D supplementation, with or without a calcium-rich diet, would promote kidney stone formation. Four groups of rats received vitamin D alone (100,000 UI/kg/3 weeks), a calcium-enriched diet alone, both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Serum and urine parameters and crystalluria were monitored. Kidney stones were assessed by 3-dimensional micro-computed tomography, infrared spectroscopy, von Kossa/Yasue staining, and field emission scanning electron microscopy. Although serum calcium levels were similar in the 4 groups, rats receiving vitamin D had a progressive increase in urinary calcium excretion over time, especially those receiving both calcium and vitamin D. However, oral calcium supplementation alone did not increase urinary calcium excretion. At 6 months, rats exposed to both calcium and vitamin D, but not rats exposed to calcium or vitamin D alone, developed significant apatite kidney calcifications (mean volume, 0.121 mm(3)). Thus, coadministration of vitamin D and increased calcium intake had a synergistic role in tubular calcifications or kidney stone formation in this rat model. Hence, one should be cautious about the cumulative risk of kidney stone formation in humans when exposed to both vitamin D supplementation and high calcium intake.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 6, UMR S 1155, Paris, France; INSERM, UMR S 1155, Paris, France; Physiology Unit, AP-HP, Hôpital Tenon, Paris, France. Electronic address: emmanuel.letavernier@tnn.aphp.fr.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Letavernier
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 6, UMR S 1155, Paris, France; INSERM, UMR S 1155, Paris, France; Urology Unit, AP-HP, Hôpital Saint-Louis, Paris, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Verrier
authors.affiliation: AST-RX Platform, UMR Centre de Recherche sur la Paléobiodiversité et les Paléoenvironnements (CR2P, UMR 7207), Sorbonne Universités-MNHN, CNRS, UPMC Univ Paris 6, Muséum national d'Histoire naturelle, Paris, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Goussard
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 6, UMR S 1155, Paris, France; INSERM, UMR S 1155, Paris, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Perez
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 6, UMR S 1155, Paris, France; INSERM, UMR S 1155, Paris, France.
authors.forename: Léa
authors.initials: L
authors.lastname: Huguet
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 6, UMR S 1155, Paris, France; INSERM, UMR S 1155, Paris, France; Physiology Unit, AP-HP, Hôpital Tenon, Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Haymann
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 6, UMR S 1155, Paris, France; INSERM, UMR S 1155, Paris, France; Physiology Unit, AP-HP, Hôpital Tenon, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Baud
authors.affiliation: Laboratoire de Physique des Solides, CNRS UMR 8502, Université Paris Sud XI, Orsay, France; CNRS, Laboratoire de Chimie de la Matière Condensée de Paris, UPMC, Collège de France, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Bazin
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 6, UMR S 1155, Paris, France; INSERM, UMR S 1155, Paris, France; Physiology Unit, AP-HP, Hôpital Tenon, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Daudon
mesh_terms: D000818:Animals; D001031:Apatites / Q000378:metabolism; D018488:Bone Demineralization, Pathologic / Q000209:etiology; D002136:Calcium, Dietary / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D019587:Dietary Supplements / Q000009:adverse effects*; D004195:Disease Models, Animal; D004357:Drug Synergism; D007669:Kidney Calculi / Q000097:blood / Q000737:chemistry / Q000209:etiology* / Q000652:urine; D008297:Male; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000378:metabolism; D065667:Renal Elimination; D017550:Spectroscopy, Fourier Transform Infrared; D014807:Vitamin D / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D001031:Apatites; D002136:Calcium, Dietary; D018167:Receptors, Calcitriol; D014807:Vitamin D
keywords: calcium; rat; urolithiasis; vitamin D