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Effect of cinacalcet on urine calcium excretion and supersaturation in genetic hypercalciuric stone-forming rats.
Kidney Int. 2006 May; 69(9):1586-92.KI

Abstract

Idiopathic hypercalciuria is the most common metabolic abnormality in patients with nephrolithiasis. Through successive inbreeding, we have developed a strain of rats whose urine calcium (UCa) excretion is approximately 8-10-fold greater than that of control rats and who spontaneously form kidney stones. We have termed these rats genetic hypercalciuric stone-forming (GHS) rats. The physiology of the hypercalciuria in the GHS rats closely parallels that of man. We have recently shown that the GHS rat kidneys have an increased number of receptors for calcium (CaR) compared to Sprague-Dawley rats, the strain of rats originally bred to develop the GHS rats. Calcimimetics, such as cinacalcet (Cin), increase the sensitivity of the CaR to Ca. The effects of Cin on UCa are complex and difficult to predict. We tested the hypothesis that Cin would alter urinary (U) Ca and supersaturation with respect to calcium hydrogen phosphate (CaHPO(4)) and calcium oxalate (CaOx). GHS or control rats were fed a normal Ca diet (0.6% Ca) for 28 days with Cin (30 mg/kg/24 h) added to the diet of half of each group for the last 14 days. The protocol was then repeated while the rats were fed a low Ca (0.02% Ca) diet. We found that Cin led to a marked reduction in circulating parathyroid hormone and a modest reduction in serum Ca. Cin did not alter UCa when the GHS rats were fed the normal Ca diet but lowered UCa when they were fed the low Ca diet. However, Cin did not alter U supersaturation with respect to either CaOx or CaHPO(4) on either diet. If these findings in GHS rats can be confirmed in man, it suggests that Cin would not be an effective agent in the treatment of human idiopathic hypercalciuria and resultant stone formation.

Authors+Show Affiliations

Nephrology Division, Department of Medicine, University of Rochester School of Medicine, Rochester, New York, USA. David_Bushinsky@URMC.Rochester.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

16557225

Citation

Bushinsky, D A., et al. "Effect of Cinacalcet On Urine Calcium Excretion and Supersaturation in Genetic Hypercalciuric Stone-forming Rats." Kidney International, vol. 69, no. 9, 2006, pp. 1586-92.
Bushinsky DA, Laplante K, Asplin JR. Effect of cinacalcet on urine calcium excretion and supersaturation in genetic hypercalciuric stone-forming rats. Kidney Int. 2006;69(9):1586-92.
Bushinsky, D. A., Laplante, K., & Asplin, J. R. (2006). Effect of cinacalcet on urine calcium excretion and supersaturation in genetic hypercalciuric stone-forming rats. Kidney International, 69(9), 1586-92.
Bushinsky DA, Laplante K, Asplin JR. Effect of Cinacalcet On Urine Calcium Excretion and Supersaturation in Genetic Hypercalciuric Stone-forming Rats. Kidney Int. 2006;69(9):1586-92. PubMed PMID: 16557225.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of cinacalcet on urine calcium excretion and supersaturation in genetic hypercalciuric stone-forming rats. AU - Bushinsky,D A, AU - Laplante,K, AU - Asplin,J R, PY - 2006/3/25/pubmed PY - 2006/6/22/medline PY - 2006/3/25/entrez SP - 1586 EP - 92 JF - Kidney international JO - Kidney Int. VL - 69 IS - 9 N2 - Idiopathic hypercalciuria is the most common metabolic abnormality in patients with nephrolithiasis. Through successive inbreeding, we have developed a strain of rats whose urine calcium (UCa) excretion is approximately 8-10-fold greater than that of control rats and who spontaneously form kidney stones. We have termed these rats genetic hypercalciuric stone-forming (GHS) rats. The physiology of the hypercalciuria in the GHS rats closely parallels that of man. We have recently shown that the GHS rat kidneys have an increased number of receptors for calcium (CaR) compared to Sprague-Dawley rats, the strain of rats originally bred to develop the GHS rats. Calcimimetics, such as cinacalcet (Cin), increase the sensitivity of the CaR to Ca. The effects of Cin on UCa are complex and difficult to predict. We tested the hypothesis that Cin would alter urinary (U) Ca and supersaturation with respect to calcium hydrogen phosphate (CaHPO(4)) and calcium oxalate (CaOx). GHS or control rats were fed a normal Ca diet (0.6% Ca) for 28 days with Cin (30 mg/kg/24 h) added to the diet of half of each group for the last 14 days. The protocol was then repeated while the rats were fed a low Ca (0.02% Ca) diet. We found that Cin led to a marked reduction in circulating parathyroid hormone and a modest reduction in serum Ca. Cin did not alter UCa when the GHS rats were fed the normal Ca diet but lowered UCa when they were fed the low Ca diet. However, Cin did not alter U supersaturation with respect to either CaOx or CaHPO(4) on either diet. If these findings in GHS rats can be confirmed in man, it suggests that Cin would not be an effective agent in the treatment of human idiopathic hypercalciuria and resultant stone formation. SN - 0085-2538 UR - https://www.unboundmedicine.com/medline/citation/16557225/Effect_of_cinacalcet_on_urine_calcium_excretion_and_supersaturation_in_genetic_hypercalciuric_stone_forming_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(15)51721-3 DB - PRIME DP - Unbound Medicine ER -