Calcium-mediated parathyroid hormone release changes in patients treated with the calcimimetic agent cinacalcet.
BACKGROUND
The parathyroid-calcium (Ca(2+)-PTH) curve expresses modulation of parathyroid hormone (PTH) secretion by the parathyroid gland as a function of changing extracellular Ca(2+) concentration. Patients with hyperparathyroidism (HPT) show a rightward shift of the curve compared with controls, suggesting a reduced sensitivity of parathyroid cells to Ca(2+). Increasing the sensitivity of the parathyroid gland to extracellular Ca(2+) by manipulation of the Ca(2+)-sensing receptor (CaR) may have therapeutic potential. Calcimimetics allosterically modify CaR and render it more sensitive to extracellular Ca(2+), accounting for the simultaneous reduction of Ca(2+) and PTH seen in most patients.


METHODS
The Ca(2+)-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 Ca(2+) concentration was used to induce hypocalcaemia and maximally stimulate PTH secretion, followed immediately by a 2-h high-dialysate Ca(2+) concentration to induce hypercalcaemia and maximally inhibit PTH secretion.


RESULTS
Significant decreases in ionized Ca(2+) and intact PTH were observed following cinacalcet treatment. Cinacalcet treatment also led to a decrease in the set point for Ca(2+) and to a leftward shift of the Ca(2+)-PTH curve. Significant differences were present in all segments of the Ca(2+)-PTH curves.


CONCLUSIONS
The pathological rightward shift of the Ca(2+)-PTH curve seen in many HPT patients may be reversed by cinacalcet treatment.
de Francisco
Angel L M
AL
Servicio de Nefrología, Hospital Universitario Valdecilla, Avda Valdecilla, s/n, Santander, 39008, Spain. martinal@unican.es
Izquierdo
Maria
M
Cunningham
John
J
Piñera
Celestino
C
Palomar
Rosa
R
Fresnedo
Gema Fernandez
GF
Amado
Jose A
JA
Unzueta
Mayte Garcia
MG
Arias
Manuel
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002118:Calcium / Q000502:physiology*; D000069449:Cinacalcet; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D009395:Nephritis, Interstitial / Q000378:metabolism; D009400:Nephrosclerosis / Q000378:metabolism; D010281:Parathyroid Hormone / Q000378:metabolism*; D007690:Polycystic Kidney Diseases / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000502:physiology*; D006435:Renal Dialysis
D009281:Naphthalenes; D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D002118:Calcium; D000069449:Cinacalcet