2008 JASN IMPACT FACTOR 7.505	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: ASN.2008111195v1 20/8/1705    most recent 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 Renkema, K. Y. Articles by Hoenderop, J. G. Search for Related Content PubMed PubMed Citation Articles by Renkema, K. Y. Articles by Hoenderop, J. G. Related Collections Related Articles

The Calcium-Sensing Receptor Promotes Urinary Acidification to Prevent Nephrolithiasis

Kirsten Y. Renkema^*, Ana Velic, Henry B. Dijkman, Sjoerd Verkaart^*, Annemiete W. van der Kemp^*, Marta Nowik, Kim Timmermans^*, Alain Doucet, Carsten A. Wagner, René J. Bindels^* and Joost G. Hoenderop^*

*Department of Physiology, Nijmegen Centre for Molecular Life Sciences, and
Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands;
Institute of Physiology and Zürich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; and
Laboratoire de Physiologie et Génomique Rénales, CNRS/UPMC UMR 7134, Institut des Cordeliers, Paris, France

Correspondence: Dr. Joost G. Hoenderop, Physiology 286, Radboud University Nijmegen Medical Centre, P.O. Box 9101, NL-6500 HB Nijmegen, Netherlands. Phone: +31-24-3610580; Fax: +31-24-3616413; E-mail: j.hoenderop{at}ncmls.ru.nl

Received for publication November 21, 2008. Accepted for publication March 10, 2009.

Hypercalciuria increases the risk for urolithiasis, but renal adaptive mechanisms reduce this risk. For example, transient receptor potential vanilloid 5 knockout (TPRV5^–/–) mice lack kidney stones despite urinary calcium (Ca²⁺) wasting and hyperphosphaturia, perhaps as a result of their significant polyuria and urinary acidification. Here, we investigated the mechanisms linking hypercalciuria with these adaptive mechanisms. Exposure of dissected mouse outer medullary collecting ducts to high (5.0 mM) extracellular Ca²⁺ stimulated H⁺-ATPase activity. In TRPV5^–/– mice, activation of the renal Ca²⁺-sensing receptor promoted H⁺-ATPase–mediated H⁺ excretion and downregulation of aquaporin 2, leading to urinary acidification and polyuria, respectively. Gene ablation of the collecting duct-specific B1 subunit of H⁺-ATPase in TRPV5^–/– mice abolished the enhanced urinary acidification, which resulted in severe tubular precipitations of Ca²⁺-phosphate in the renal medulla. In conclusion, activation of Ca²⁺-sensing receptor by increased luminal Ca²⁺ leads to urinary acidification and polyuria. These beneficial adaptations facilitate the excretion of large amounts of soluble Ca²⁺, which is crucial to prevent the formation of kidney stones.

Related Articles

This Month's Highlights
J. Am. Soc. Nephrol. 2009 20: A12. [Full Text] [PDF]

This article has been cited by other articles:

				G. Vezzoli, A. Terranegra, T. Arcidiacono, G. Gambaro, L. Milanesi, E. Mosca, L. Soldati, and On behalf of GENIAL network (Genetics and Environm Calcium kidney stones are associated with a haplotype of the Calcium-sensing receptor gene regulatory region Nephrol. Dial. Transplant., January 12, 2010; (2010) gfp760v1. [Abstract] [Full Text] [PDF]

				E. M. Worcester and F. L. Coe Does Idiopathic Hypercalciuria Trigger Calcium-Sensing Receptor-Mediated Protection from Urinary Supersaturation? J. Am. Soc. Nephrol., August 1, 2009; 20(8): 1657 - 1659. [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673