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NDT Advance Access originally published online on April 11, 2008
Nephrology Dialysis Transplantation 2008 23(9):2761-2767; doi:10.1093/ndt/gfn143
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© The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org


Cinacalcet does not affect longitudinal growth but increases body weight gain in experimental uraemia

Kumiko Nakagawa1, Eduardo C. Pérez2, Jun Oh1, Fernando Santos2, Aman Geldyyev3, Marie -L. Gross3, Franz Schaefer1 and Claus P. Schmitt1

1 University Hospital for Pediatric & Adolescent Medicine, University of Heidelberg, Germany 2 Department of Pediatrics, Hospital Universitario Central de Asturias, University of Oviedo, Spain 3 Institute of Pathology, University of Heidelberg, Germany

Correspondence and offprint requests to: Claus Peter Schmitt, Division of Pediatric Nephrology, University Hospital for Pediatric and Adolescent Medicine, Im Neuenheimer Feld 153, 69120 Heidelberg, Germany. Tel: +49-6221-56-39313; Fax: +49-6221-56-4203; E-mail: claus.peter.schmitt{at}med.uni-heidelberg.de



  Abstract

Background. Cinacalcet (CIN) efficiently suppresses parathyroid hormone (PTH) secretion by the activation of the calcium-sensing receptor (CaR). Epiphyseal chondrocytes also express the CaR and its activation promotes cell proliferation and differentiation in vitro. Hence, the impact of CIN on the growth plate function requires assessment before routine administration in children.

Methods. We treated subtotally nephrectomized (SNX) and sham-operated, ad lib and pair-fed Sprague-Dawley rats with CIN (15 mg/kg day) or solvent (S) for 14 days p.o. and assessed whole body and tibia length gain, growth plate morphology, osseous front advance (OFA) (calcein staining) and chondrocyte proliferation rate [5-bromo-2'-deoxyuridine (BrdU) staining].

Results. Total body length gain did not differ after 7 and 14 days (SNX + CIN 2.9 ± 0.6, SNX + S 3.0 ± 0.7; sham + CIN 4.2 ± 0.4, sham + S 4.5 ± 0.4; sham pair-fed + CIN 3.3 ± 0.5, sham pair-fed + S 3.5 ± 0.6 cm/14 days; P = n.s.). Tibia length, the height of the total growth plate and the hypertrophic zone, OFA and chondrocyte proliferation rate were similar with CIN and S. Serum Ca2+ declined with CIN treatment; PTH was 61% lower in CIN- compared to S-treated SNX (P < 0.05). Food intake was similar, whereas body weight gain (21.6 ± 8.7 versus 12.7 ± 11.2 g) and body weight gain per food intake (141 ± 50 versus 77 ± 70 g/kg) improved in CIN- versus S-treated SNX animals (P < 0.05).

Conclusion. CIN treatment does not impact on growth plate chondrocyte function in uraemic rats, but improves food efficiency and body weight gain.

Keywords: calcimimetic agents; calcium receptor; growth plate chondrocyte; longitudinal growth; rats

Received for publication: 2. 7.07
Accepted in revised form: 21. 2.08


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