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.