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Persistence of 1,25D-induced hypercalciuria in alendronate-treated genetic hypercalciuric stone-forming rats fed a low-calcium diet.
Am J Physiol Renal Physiol. 2014 May 01; 306(9):F1081-7.AJ

Abstract

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.

Authors+Show Affiliations

Research Assistant Professor of Medicine, Univ. of Rochester School of Medicine and Dentistry, Division of Nephrology, Dept. of Medicine, 601 Elmwood Ave., Box 675, Rochester, NY 14642. Kevin_Frick@URMC.Rochester.edu.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24573387

Citation

Frick, Kevin K., et al. "Persistence of 1,25D-induced Hypercalciuria in Alendronate-treated Genetic Hypercalciuric Stone-forming Rats Fed a Low-calcium Diet." American Journal of Physiology. Renal Physiology, vol. 306, no. 9, 2014, pp. F1081-7.
Frick KK, Asplin JR, Culbertson CD, et al. Persistence of 1,25D-induced hypercalciuria in alendronate-treated genetic hypercalciuric stone-forming rats fed a low-calcium diet. Am J Physiol Renal Physiol. 2014;306(9):F1081-7.
Frick, K. K., Asplin, J. R., Culbertson, C. D., Granja, I., Krieger, N. S., & Bushinsky, D. A. (2014). Persistence of 1,25D-induced hypercalciuria in alendronate-treated genetic hypercalciuric stone-forming rats fed a low-calcium diet. American Journal of Physiology. Renal Physiology, 306(9), F1081-7. https://doi.org/10.1152/ajprenal.00680.2013
Frick KK, et al. Persistence of 1,25D-induced Hypercalciuria in Alendronate-treated Genetic Hypercalciuric Stone-forming Rats Fed a Low-calcium Diet. Am J Physiol Renal Physiol. 2014 May 1;306(9):F1081-7. PubMed PMID: 24573387.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Persistence of 1,25D-induced hypercalciuria in alendronate-treated genetic hypercalciuric stone-forming rats fed a low-calcium diet. AU - Frick,Kevin K, AU - Asplin,John R, AU - Culbertson,Christopher D, AU - Granja,Ignacio, AU - Krieger,Nancy S, AU - Bushinsky,David A, Y1 - 2014/02/26/ PY - 2014/2/28/entrez PY - 2014/2/28/pubmed PY - 2014/6/20/medline KW - bone resorption KW - calcium KW - intestinal absorption KW - kidney stones KW - vitamin D SP - F1081 EP - 7 JF - American journal of physiology. Renal physiology JO - Am. J. Physiol. Renal Physiol. VL - 306 IS - 9 N2 - 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. SN - 1522-1466 UR - https://www.unboundmedicine.com/medline/citation/24573387/Persistence_of_125D_induced_hypercalciuria_in_alendronate_treated_genetic_hypercalciuric_stone_forming_rats_fed_a_low_calcium_diet_ L2 - http://www.physiology.org/doi/full/10.1152/ajprenal.00680.2013?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -