NDT Advance Access first published online on April 19, 2008
This version published online on April 23, 2008
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfn191
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Calcium-mediated parathyroid hormone release changes in patients treated with the calcimimetic agent cinacalcet
1 Nephrology Service, Valdecilla University Hospital, University of Cantabria, Santander, Spain 2 Centre for Nephrology, The Royal Free and University College Medical School, London, UK 3 Endocrinology Service, Valdecilla University Hospital, University of Cantabria, Santander, Spain
Correspondence and offprint requests to: Angel L. M. de Francisco, Servicio de Nefrología, Hospital Universitario Valdecilla, Avda Valdecilla, s/n, Santander, 39008, Spain. Tel: +34-942-202-738; Fax: +34-942-320-415; E-mail: martinal{at}unican.es
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Abstract |
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Background. The parathyroid-calcium (Ca2+-PTH) curve expresses modulation of parathyroid hormone (PTH) secretion by the parathyroid gland as a function of changing extracellular Ca2+ concentration. Patients with hyperparathyroidism (HPT) show a rightward shift of the curve compared with controls, suggesting a reduced sensitivity of parathyroid cells to Ca2+. Increasing the sensitivity of the parathyroid gland to extracellular Ca2+ by manipulation of the Ca2+-sensing receptor (CaR) may have therapeutic potential. Calcimimetics allosterically modify CaR and render it more sensitive to extracellular Ca2+, accounting for the simultaneous reduction of Ca2+ and PTH seen in most patients.
Methods. The Ca2+-PTH curve was evaluated in 10 haemodialysis patients, with baseline intact PTH levels >300 pg/ml in two haemodialysis sessions, one before and the other after (range, 9–22 weeks) cinacalcet treatment. In each session a 2-h low-dialysate Ca2+ concentration was used to induce hypocalcaemia and maximally stimulate PTH secretion, followed immediately by a 2-h high-dialysate Ca2+ concentration to induce hypercalcaemia and maximally inhibit PTH secretion.
Results. Significant decreases in ionized Ca2+ and intact PTH were observed following cinacalcet treatment. Cinacalcet treatment also led to a decrease in the set point for Ca2+ and to a leftward shift of the Ca2+-PTH curve. Significant differences were present in all segments of the Ca2+-PTH curves.
Conclusion. The pathological rightward shift of the Ca2+-PTH curve seen in many HPT patients may be reversed by cinacalcet treatment.
Keywords: calcimimetic; calcium sensing receptor; calcium; cinacalcet; hyperparathyroidism; parathyroid hormone; Ca2+-PTH curve
Received for publication: 28. 8.07
Accepted in revised form: 12. 3.08
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