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.


CONCLUSIONS
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.
Department of Medicine III, Division of Nephrology and Dialysis, Medical University Vienna, Vienna, Austria. kyra.borchhardt@meduniwien.ac.at
Kyra A
KA
Borchhardt
Harald
H
Heinzl
Elisabeth
E
Mayerwöger
Walter H
WH
Hörl
Martin
M
Haas
Gere
G
Sunder-Plassmann
D000328:Adult; D000368:Aged; D002118:Calcium / Q000097:blood / Q000652:urine*; D000069449:Cinacalcet; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D006961:Hyperparathyroidism / Q000188:drug therapy* / Q000209:etiology / Q000652:urine; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007674:Kidney Diseases / Q000145:classification / Q000150:complications / Q000601:surgery; D007676:Kidney Failure, Chronic / Q000601:surgery; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000188:drug therapy / Q000652:urine
D007166:Immunosuppressive Agents; D009281:Naphthalenes; D002118:Calcium; D000069449:Cinacalcet