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Published ahead of print on May 14, 2008
Clinical Journal of the American Society of Nephrology
© 2008 American Society of Nephrology
doi: 10.2215/CJN.00240108
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Received January 15, 2008
Accepted on April 11, 2008

ORIGINAL ARTICLES

RANKL Is a Mediator of Bone Resorption in Idiopathic Hypercalciuria

Samirah Abreu Gomes *, Luciene Machado dos Reis {dagger}, Irene Lourdes Noronha {dagger}, Vanda Jorgetti {dagger}, and Ita Pfeferman Heilberg *1

*Nephrology Division, Universidade Federal de São Paulo, and {dagger}Nephrology Division, Universidade de São Paulo, São Paulo, Brazil


1 To whom correspondence should be addressed. E-mail: ipheilberg{at}nefro.epm.br.


   Abstract

Background and objectives: This study aimed to determine the expression of osteoprotegerin, receptor activator of nuclear factor {kappa}B ligand, interleukin-1{alpha}, transforming growth factor-{beta}, and basic fibroblast growth factor in stone-forming patients with idiopathic hypercalciuria.

Design, setting, participants, & measurements: Immunohistochemical analysis was performed in undecalcified bone samples previously obtained from 36 transiliac bone biopsies of patients who had idiopathic hypercalciuria and whose histomorphometry had shown lower bone volume, increased bone resorption, and prolonged mineralization lag time.

Results: Bone expression of receptor activator of nuclear factor {kappa}B ligand and osteoprotegerin was significantly higher in patients with idiopathic hypercalciuria versus control subjects. Transforming growth factor-{beta} immunostaining was lower in patients with idiopathic hypercalciuria than in control subjects and correlated directly with mineralization surface. Interleukin-1{alpha} and basic fibroblast growth factor staining did not differ between groups. Receptor activator of nuclear factor {kappa}B ligand bone expression was significantly higher in patients who had idiopathic hypercalciuria and exhibited higher versus normal bone resorption.

Conclusion: A higher expression of receptor activator of nuclear factor {kappa}B ligand in bone tissue suggests that increased bone resorption in patients with idiopathic hypercalciuria is mediated by receptor activator of nuclear factor {kappa}B ligand. Osteoprotegerin bone expression might have been secondarily increased in an attempt to counteract the actions of receptor activator of nuclear factor {kappa}B ligand. The low bone expression of transforming growth factor-{beta} could contribute to the delayed mineralization found in such patients.







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