Journal Article

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

Kumiko Nakagawa, Eduardo C. Pérez, Jun Oh, Fernando Santos, Aman Geldyyev, Marie -L. Gross, Franz Schaefer and Claus P. Schmitt

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 23, issue 9, pages 2761-2767
Published in print September 2008 | ISSN: 0931-0509
Published online April 2008 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfn143
Cinacalcet does not affect longitudinal growth but increases body weight gain in experimental uraemia

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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

Journal Article.  4419 words.  Illustrated.

Subjects: Nephrology

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