Persistence of 1,25D-induced hypercalciuria in alendronate-treated genetic hypercalciuric stone-forming rats fed a low-calcium diet
| Autor: | Nancy Krieger, Ignacio Granja, John R. Asplin, Christopher D. Culbertson, David A. Bushinsky, Kevin K. Frick |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Calcitriol Genotype Physiology Hypercalciuria chemistry.chemical_element Calcium Kidney Intestinal absorption Bone resorption Rats Sprague-Dawley Kidney Calculi Bone Density Internal medicine medicine Animals Bone Resorption Intestinal Mucosa Alendronate Bone Density Conservation Agents Reabsorption medicine.disease Rats Calcium Dietary Disease Models Animal medicine.anatomical_structure Endocrinology Phenotype chemistry Intestinal Absorption Kidney stones hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | American journal of physiology. Renal physiology. 306(9) |
| ISSN: | 1522-1466 |
| Popis: | Genetic hypercalciuric stone-forming (GHS) rats demonstrate increased intestinal Ca absorption, increased bone resorption, and reduced renal tubular Ca reabsorption leading to hypercalciuria and all form kidney stones. GHS have increased vitamin D receptors (VDR) at these sites of Ca transport. Injection of 1,25(OH)2D3 (1,25D) leads to a greater increase in urine (u)Ca in GHS than in control Sprague-Dawley (SD), possibly due to the additional VDR. In GHS the increased uCa persists on a low-Ca diet (LCD) suggesting enhanced bone resorption. We tested the hypothesis that LCD, coupled to inhibition of bone resorption by alendronate (alen), would eliminate the enhanced 1,25D-induced hypercalciuria in GHS. SD and GHS were fed LCD and half were injected daily with 1,25D. After 8 days all were also given alen until euthanasia at day 16. At 8 days, 1,25D increased uCa in SD and to a greater extent in GHS. At 16 days, alen eliminated the 1,25D-induced increase in uCa in SD. However, in GHS alen decreased, but did not eliminate, the 1,25D-induced hypercalciuria, suggesting maximal alen cannot completely prevent the 1,25D-induced bone resorption in GHS, perhaps due to increased VDR. There was no consistent effect on mRNA expression of renal transcellular or paracellular Ca transporters. Urine CaP and CaOx supersaturation (SS) increased with 1,25D alone in both SD and GHS. Alen eliminated the increase in CaP SS in SD but not in GHS. If these results are confirmed in humans with IH, the use of bisphosphonates, such as alen, may not prevent the decreased bone density observed in these patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|