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Increased Osteoblastic Activity and Expression of Receptor Activator of NF-B Ligand in Nonuremic Nephrotic Syndrome

Michael Freundlich^*, Evelyn Alonzo, Ezequiel Bellorin-Font and Jose R. Weisinger

^* Department of Pediatrics, University of Miami, Miami, and Pediatric Specialty Center, Hollywood, Florida; and Division of Nephrology, Hospital Universitario de Caracas and Universidad Central de Venezuela, Caracas, Venezuela

Address correspondence to: Dr. Michael Freundlich, 8940 N. Kendall Drive, #603 E, Miami, FL 33176. Phone: 305-271-4211; Fax: 305-538-0907; E-mail: mfmefex{at}pol.net

Received for publication December 8, 2004. Accepted for publication March 31, 2005.

Patients with nephrotic syndrome (NS), even with normal GFR, often display altered mineral homeostasis and abnormal bone histology. However, the latter, mostly osteomalacia and increased bone resorption, cannot be readily explained by the prevalent concentrations of parathyroid hormone and vitamin D metabolites. The transmembrane receptor activator of NF-B ligand (RANKL) of osteoblasts is essential for osteoclast formation and differentiation. Osteoblasts activity and the expression of RANKL were tested in cultures of normal human osteoblasts with sera obtained from patients with NS and normal GFR (129 ± 26 ml/min per 1.73 m²) during relapse and remission of their NS. Osteoblasts that were cultured in vitro with sera during relapse displayed elevated concentrations of alkaline phosphatase (AP) and increased expression of RANKL. By contrast, during remission, AP concentrations were significantly lower (P < 0.05) and RANKL expression notably attenuated or absent. AP correlated with the proteinuria (r = 0.5, P < 0.05) and was not significantly affected by the therapeutic administration of corticosteroids. Whereas parathyroid hormone levels were normal (35 ± 21 pg/ml), the serum markers of bone formation (osteocalcin and bone-specific alkaline phosphatase) were lower during relapse compared with remission. Thus, sera from patients with NS and normal GFR stimulate the activity of osteoblasts and upregulate their expression of RANKL. These alterations, more prominent during clinically active NS, are transient and reversible upon remission. These disturbances of bone biology may play an important pathogenic role in the abnormal bone histology observed in patients with NS even before a decline in GFR occurs.

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				S. A. Gomes, L. M. dos Reis, I. L. Noronha, V. Jorgetti, and I. P. Heilberg RANKL Is a Mediator of Bone Resorption in Idiopathic Hypercalciuria Clin. J. Am. Soc. Nephrol., September 1, 2008; 3(5): 1446 - 1452. [Abstract] [Full Text] [PDF]

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