Cinacalcet decreases bone formation rate in hypercalcemic hyperparathyroidism after kidney transplantation.

BACKGROUND/AIMS: Cinacalcet reduces serum calcium in kidney transplant recipients with hypercalcemic hyperparathyroidism. Its effect on bone, however, has not been investigated in this population. METHODS: We prospectively examined bone turnover, histomorphometry and density as well as serum bone biomarkers in 10 transplant recipients before and after treatment with cinacalcet. RESULTS: After 18-24 months of treatment with cinacalcet, bone formation decreased in 7, increased in 2, and remained zero in 1 patient (p = 0.11). Trabecular bone volume was maintained. Trabecular number decreased (p = 0.03), but trabecular thickness was unchanged (p = 0.17). Osteoid decreased (p = 0.02) and osteoblast surface increased (p = 0.02). Bone mineral density of the femur remained stable in 1 patient, decreased in 2 patients, but increased in 7 patients (p = 0.153). Serum calcium concentration (p = 0.005), iPTH (p = 0.01) and calcitonin concentration decreased (p = 0.03), while 25(OH) vitamin D(3) increased (p = 0.02). No fractures were reported. Graft function remained stable. CONCLUSION: While cinacalcet might decrease bone formation rate, it did not change bone volume, and bone mineral density of the femur increased. Therefore, the use of cinacalcet in hypercalcemic hyperparathyroidism might be safe with regard to the bone disease present after kidney transplantation.

Cinacalcet increases calcium excretion in hypercalcemic hyperparathyroidism after kidney transplantation.

BACKGROUND: Cinacalcet reduces serum calcium in kidney transplant recipients with hypercalcemic hyperparathyroidism. The mechanism of action is not fully understood. We hypothesized that cinacalcet increases renal elimination of calcium, thereby improving hypercalcemia in kidney transplant recipients. METHODS: We prospectively examined the effect of cinacalcet (30 mg/d) during the first 6 weeks of treatment on serum and 24 hrs urinary calcium concentration and calculated fractional calcium excretion in 32 patients with sustained hypercalcemic hyperparathyroidism (Ca >2.6 mmol/L [10.4 mg/dL], intact parathyroid hormone >60 pg/mL). Secondary endpoints were serum phosphate and tubular maximum of phosphate corrected for glomerular filtration rate, intact parathyroid hormone and serum creatinine. RESULTS: Serum calcium concentrations decreased in all patients (from 2.77 to 2.51 mmol/L; P<0.0001), fractional calcium excretion increased rapidly in the first 2 weeks of treatment from 1.06 to 1.78% (P<0.0001), and decreased thereafter to 1.37% (P<0.05 vs. early treatment). Simultaneously serum phosphate and tubular maximum of phosphate corrected for glomerular filtration rate increased significantly from 0.79 to 0.85 to 0.88 mmol/L (P<0.05), and from 0.52 to 0.61 (P<0.005) and 0.62 (P<0.0001 vs. baseline), respectively. Intact parathyroid hormone did not decrease significantly. Serum creatinine remained stable. CONCLUSION: We provide evidence that the calcium lowering effect of cinacalcet in patients with persistent hyperparathyroidism after kidney transplantation is caused, at least in part, by increased urinary calcium excretion.

Reversibility of 'secondary hypercalcitoninemia' after kidney transplantation.

Whether the increase of calcitonin (CT) concentration in patients with chronic kidney disease (CKD) is reversible or not after kidney transplantation is not known. We examined the effect of kidney transplantation on basal and pentagastrin-stimulated CT in CKD patients with elevated screening CT levels. Before transplantation, the median basal CT concentration of 17 patients was 31 pg/mL (13-76), and decreased to 8 pg/mL (4-28) at 23 months (2-34) after kidney transplantation (p < 0.00005). The maximum concentration of pentagastrin-stimulated CT was 63 pg/mL (25-110) before transplantation and decreased to 20 pg/mL (8-91) (p < 0.00005) thereafter. There was a linear association between CT and calcium as well as between phosphorus and parathyroid hormone at the time of screening. After transplantation, CT correlated with serum creatinine. Therefore, the increase of CT concentration in patients with impaired kidney function presumably reflects 'secondary hypercalcitoninemia' due to C-cell hyperactivity.