Vitamin D and Calcium Supplementation Accelerates Randall's Plaque Formation in a Murine Model.

Abstract

Most kidney stones are made of calcium oxalate crystals. Randall's plaque, an apatite deposit at the tip of the renal papilla, is considered to at the origin of these stones. Hypercalciuria may promote Randall's plaque formation and growth. We analyzed whether long-term exposure of Abcc6-/- mice (a murine model of Randall's plaque) to vitamin D supplementation, with or without a calcium-rich diet, would accelerate the formation of Randall's plaque. Eight groups of mice (including Abcc6-/- and wild type) received vitamin D alone (100,000 UI/kg every 2 weeks), a calcium-enriched diet alone (calcium gluconate 2 g/L in drinking water), both vitamin D supplementation and a calcium-rich diet, or a standard diet (controls) for 6 months. Kidney calcifications were assessed by 3-dimensional microcomputed tomography, μ-Fourier transform infrared spectroscopy, field emission-scanning electron microscopy, transmission electron microscopy, and Yasue staining. At 6 months, Abcc6-/- mice exposed to vitamin D and calcium supplementation developed massive Randall's plaque when compared with control Abcc6-/- mice (P < 0.01). Wild-type animals did not develop significant calcifications when exposed to vitamin D. Combined administration of vitamin D and calcium significantly accelerates Randall's plaque formation in a murine model. This original model raises concerns about the cumulative risk of vitamin D supplementation and calcium intakes in Randall's plaque formation.

• Authors: Elise Bouderlique, Ellie Tang, Joëlle Perez, Amélie Coudert, Dominique Bazin, Marie-Christine Verpont, Christophe Duranton, Isabelle Rubera, Jean-Philippe Haymann, Georges Leftheriotis, Ludovic Martin, Michel Daudon, Emmanuel Letavernier
• Journal: The American journal of pathology (Am J Pathol) Vol. 189 Issue 11 Pg. 2171-2180 (11 2019) ISSN: 1525-2191 [Electronic] United States
• PMID: 31449775 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Abcc6 protein, mouse
• Calcium, Dietary
• Multidrug Resistance-Associated Proteins
• Vitamin D

Topics

• Animals
• Calcinosis (chemically induced, metabolism, pathology)
• Calcium, Dietary (administration & dosage, adverse effects)
• Dietary Supplements (adverse effects)
• Disease Models, Animal
• Disease Progression
• Female
• Kidney Calculi (chemically induced, metabolism, pathology)
• Kidney Medulla (metabolism, pathology)
• Mice
• Mice, 129 Strain
• Mice, Inbred C57BL
• Mice, Knockout
• Multidrug Resistance-Associated Proteins (genetics)
• Time Factors
• Vitamin D (administration & dosage, adverse effects)