Hypercalcemia secondary to persistent hyperparathyroidism in kidney transplant patients: analysis after a year with cinacalcet.

INTRODUCTION: The most common cause of hypercalcemia in patients with transplanted kidneys is persistent hyperparathyroidism, which presents in 10%-30% of patients with functioning renal grafts. In these patients, the treatment of vitamin D-resistant hyperparathyroidism traditionally required parathyroidectomy. Calcimimetic agents represent a new therapeutic alternative; they inhibit parathyroid hormone (PTH) secretion, increasing the sensitivity of the calcium-sensitive receptor in the parathyroid gland. The objective of this study is to evaluate the efficacy of cinacalcet in renal transplant patients with persistent hyperparathyroidism. METHODS: Cinacalcet 30 mg/day was prescribed to 17 renal transplant patients (6 women, 11 men) with a mean age of 49 years and hypercalcemia secondary to persistent hyperparathyroidism. The treatment started 58.17 ± 35.16 months posttransplant, with 1 year of follow-up. RESULTS: Calcium in serum fell from 10.5 ± 0.74 to 9.4 ± 0.84 mg/dL (p<0.001), whereas phosphorous levels were not significantly altered. The fall in PTH was from 204.79 ± 78 to 148.55 ± 56 pg/mL (p<0.011). Kidney function remained stable, and immunosuppressant drug levels remained unchanged. The dose of cinacalcet was increased to 60 mg in 2 patients. No significant adverse effects were described, and none of the patients had to suspend the treatment. CONCLUSIONS: Calcimimetic agents represent a therapeutic alternative in transplant patients with persistent hyperparathyroidism, as they correct hypercalcemia and reduce PTH levels with no adverse effects on kidney function. Prospective, controlled studies should be designed to evaluate the long-term effects and evolution after suspension of the treatment.

Treatment with intermittent calcitriol and calcium reduces bone loss after renal transplantation.

BACKGROUND: Bone loss occurs during the first 6 months after renal transplantation (RT), and corticosteroid therapy plays an important role. Although calcium plus vitamin D administration prevents corticosteroid-induced osteoporosis, its use in RT recipients is limited by the risk of hypercalcemia. METHODS: This double-blind, randomized, and controlled prospective intervention trial examined the effect of intermittent calcitriol (0.5 microg/48 h) during the first 3 months after RT, plus oral calcium supplementation (0.5 g/day) during 1 year with calcium supplementation alone. The primary outcome measure was the change in bone mineral density (BMD) at 3 and 12 months after RT; we also explored whether the effect of calcitriol on BMD was different among vitamin D receptor (VDR) genotypes (BsmI). Forty-five recipients were randomized to calcitriol therapy (CT) and 41 were randomized to placebo (PL). RESULTS: Both groups had a similar degree of pre-existing hyperparathyroidism (197 +/- 229 vs. 191 +/- 183 pg/mL), but a more pronounced decrease of parathyroid hormone (PTH) levels after RT was observed in CT patients (at 3 months: 61.4 +/- 42.2 vs. 85.7 +/- 53.1 pg/mL, P= 0.02; at 12 months: 67.3 +/- 33.7 vs. 82.6 +/- 37 pg/mL; P= 0.08). CT patients preserved their BMD at the total hip significantly better than those on PL (3 months: 0.04 +/- 3.3 vs. -1.93 +/- 3.2%, P= 0.01; 12 months: 0.32 +/- 4.8 vs. -2.17 +/- 4.4%, P= 0.03); significant differences were noted at the intertrochanter, trochanter, and Ward's triangle. Differences did not reach significance at the femoral neck. Two CT patients (4.4%) and 4 PL patients (9.8%) developed a hypercalcemic episode during the first 3 months after RT. The effect of CT on BMD at 3 months was more prominent in recipients with the at-risk allele of the VDR gene (P= 0.03). CONCLUSION: Therapy with low-dose calcium supplements during 1 year, plus intermittent calcitriol for 3 months after RT, is safe, decreases PTH levels more rapidly, and prevents bone loss at the proximal femur; a more pronounced effect is seen in recipients with at least one at-risk allele of the VDR genotype.