2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by CHIN, J. Articles by FOX, J. Search for Related Content PubMed PubMed Citation Articles by CHIN, J. Articles by FOX, J.

Activation of the Calcium Receptor by a Calcimimetic Compound Halts the Progression of Secondary Hyperparathyroidism in Uremic Rats

JI CHIN^*, SCOTT C. MILLER^*, MICHIHITO WADA, NOBUO NAGANO, EDWARD F. NEMETH^* and JOHN FOX^*

^* NPS Pharmaceuticals, Inc., Salt Lake City, Utah
Pharmaceutical Development Laboratory, Kirin Brewery Co., Ltd., Takasaki-shi, Gunma, Japan.

Correspondence to Dr. John Fox, NPS Pharmaceuticals, Inc., 420 Chipeta Way, Salt Lake City, UT 84108. Phone: 801-583-4939; Fax: 801-583-4961; E-mail: jfox{at}npsp.com

Abstract. The secondary hyperparathyroidism that develops in rats with chronic renal insufficiency (CRI) can be totally prevented by activation of the parathyroid Ca²⁺ receptor with a calcimimetic compound, when treatment is initiated before parathyroid cell hyperplasia and increased circulating parathyroid hormone levels develop. In clinical practice, however, secondary hyperparathyroidism is usually manifest by the time CRI is diagnosed. This study examined the effects of daily oral gavage or continuous subcutaneous infusion for 8 wk of the calcimimetic NPS R-568 on the progression of established mild or moderate-to-severe secondary hyperparathyroidism in rats with CRI induced by 5/6 nephrectomy. Both oral and infused NPS R-568 completely prevented further hyperplasia but did not reduce total parathyroid cell number below that present at the initiation of treatment. This prevention of cellular proliferation occurred despite increases in plasma phosphate and decreases in Ca²⁺ and 1,25-dihydroxyvitamin D levels, and supports the view that the Ca²⁺ receptor is the dominant regulator of parathyroid cell hyperplasia in addition to parathyroid hormone secretion. The clinical implications of these findings suggest that controlling Ca²⁺ receptor activity with calcimimetic compounds could be sufficient to manage secondary hyperparathyroidism in CRI.

This article has been cited by other articles:

				H. Komaba and M. Fukagawa Regression of parathyroid hyperplasia by calcimimetics--fact or illusion? Nephrol. Dial. Transplant., December 22, 2008; (2008) gfn717v1. [Full Text] [PDF]

				H. Komaba, M. Tanaka, and M. Fukagawa Reply Nephrol. Dial. Transplant., November 5, 2008; (2008) gfn587v1. [Full Text] [PDF]

				E. F. Nemeth Anabolic Therapy for Osteoporosis: Calcilytics IBMS BoneKEy, June 1, 2008; 5(6): 196 - 208. [Abstract] [Full Text] [PDF]

				T. Drueke, D. Martin, and M. Rodriguez Can calcimimetics inhibit parathyroid hyperplasia? Evidence from preclinical studies Nephrol. Dial. Transplant., July 1, 2007; 22(7): 1828 - 1839. [Full Text] [PDF]

				G. J. Strewler A 64-Year-Old Woman With Primary Hyperparathyroidism JAMA, April 13, 2005; 293(14): 1772 - 1779. [Full Text] [PDF]

				M. Xu, S. Choudhary, D. Goltzman, F. Ledgard, D. Adams, G. Gronowicz, B. Koczon-Jaremko, L. Raisz, and C. Pilbeam Do Cyclooxygenase-2 Knockout Mice Have Primary Hyperparathyroidism? Endocrinology, April 1, 2005; 146(4): 1843 - 1853. [Abstract] [Full Text] [PDF]

				M. Mizobuchi, I. Hatamura, H. Ogata, F. Saji, S. Uda, K. Shiizaki, T. Sakaguchi, S. Negi, E. Kinugasa, S. Koshikawa, et al. Calcimimetic Compound Upregulates Decreased Calcium-Sensing Receptor Expression Level in Parathyroid Glands of Rats with Chronic Renal Insufficiency J. Am. Soc. Nephrol., October 1, 2004; 15(10): 2579 - 2587. [Abstract] [Full Text] [PDF]

				H. Ogata, E. Ritz, G. Odoni, K. Amann, and S. R. Orth Beneficial Effects of Calcimimetics on Progression of Renal Failure and Cardiovascular Risk Factors J. Am. Soc. Nephrol., April 1, 2003; 14(4): 959 - 967. [Abstract] [Full Text] [PDF]

				M. Wada and N. Nagano Control of parathyroid cell growth by calcimimetics Nephrol. Dial. Transplant., March 1, 2003; 18(90003): iii13 - 17. [Abstract] [Full Text] [PDF]

				N. Nagano, S. Miyata, S. Obana, N. Kobayashi, M. Abe, N. Fukushima, and M. Wada Sevelamer hydrochloride, a calcium-free phosphate binder, inhibits parathyroid cell proliferation in partially nephrectomized rats Nephrol. Dial. Transplant., March 1, 2003; 18(90003): iii81 - 85. [Abstract] [Full Text] [PDF]

				W. G. Goodman Calcimimetic agents and secondary hyperparathyroidism: treatment and prevention Nephrol. Dial. Transplant., February 1, 2002; 17(2): 204 - 207. [Full Text] [PDF]

				N. Nagano, S. Miyata, S. Obana, M. Ozai, N. Kobayashi, N. Fukushima, S. K. Burke, and M. Wada Sevelamer hydrochloride (Renagel(R)), a non-calcaemic phosphate binder, arrests parathyroid gland hyperplasia in rats with progressive chronic renal insufficiency Nephrol. Dial. Transplant., September 1, 2001; 16(9): 1870 - 1878. [Abstract] [Full Text] [PDF]

				A. Jara, S. Gonzalez, A. J. Felsenfeld, C. Chacon, A. Valdivieso, R. Jalil, and B. Chuaqui Failure of high doses of calcitriol and hypercalcaemia to induce apoptosis in hyperplastic parathyroid glands of azotaemic rats Nephrol. Dial. Transplant., March 1, 2001; 16(3): 506 - 512. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673