The calcimimetic cinacalcet normalizes serum calcium in renal transplant patients with persistent hyperparathyroidism

Background. Treatment of persistent hyperparathyroidism in renal transplant patients resistant to calcium and vitamin D sterols is limited and often requires parathyroldectomy. Given the potential hazards linked to surgery, an alternative approach to manage excess parathyroid hormone (PTH) secretion is needed. Calcimimetics inhibit PTH secretion by modulating the calcium-sensing receptor in the parathyroid. Lowering of the serum calcium concentration with the calcimimetic cinacalcet has previously been demonstrated in patients with primary hyperparathyroidism or with secondary hyperparathyroidism on dialysis. Here we present the first clinical observations of a calcimimetic in patients with persistent hyperparathyroidism. Methods. A 30 mg dose of cinacalcet was prescribed once daily for 3 months to seven female and seven male stable renal transplant patients, aged 23-65 years, 7 months to 14 years after transplantation, with a serum creatinine ranging from 89 to 229 mu mol/l and persistent hyperparathyroidism. Concomitant medication included cyclosporin and low-dose prednisone in all patients. Results. On cinacalcet, serum calcium decreased and normalized in all but two patients (baseline 2.72 +/- 0.03 mmol/l; 1 month 2.42 +/- 0.04 mmol/l, P < 0.001), whereas serum PTH and phosphate levels did not change significantly. A slight reduction in renal function, as assessed by serum creatinine concentration, was observed at months 2 and 3 (P < 0.05). An immunoglobulin-deficient patient developed colitis after 1 week of treatment and cinacalcet was withdrawn. No patient stopped cinacalcet because of other presumed side effects. Conclusion. Calcimimetics are a promising therapy in renal transplant patients with persistent hyperparathyroidism. Prospective controlled studies must now be designed focusing on functionally relevant musculoskeletal end-points and allowing the exclusion of negative effects on long-term renal and general outcome of such patients.