Intravenous calcitriol for treatment of hyperparathyroidism in children on hemodialysis
This double-blind, placebo-controlled study evaluated the safety and efficacy of intravenous (IV) calcitriol (Calcijex) for treatment of secondary hyperparathyroidism (2°HPT) in pediatric end-stage renal disease (ESRD) patients on hemodialysis (HD). After a 2 to 6-week washout period of all vitamin D compounds, patients with two consecutive PTH values >400 pg mL−1, calcium levels ≤10.5 mg dL−1 and calcium×phosphorus product values ≤70 mg2 dL−2 were eligible for the treatment phase. Patients received a bolus injection of calcitriol or placebo three times a week, immediately after dialysis for up to 12 weeks. Initial doses (0.5–1.5 μg) were based on the severity of 2ºHPT. The dose was increased every two weeks by 0.25 μg until there was at least a 30% decrease in PTH from baseline, or Ca>11.0 mg dL−1, or Ca×P>75 mg2 dL−2. Overall, 11/21 (52%) patients in the calcitriol group had two consecutive ≥30% decreases from baseline in serum PTH compared with 5/26 (19%) patients in the placebo group (P=0.03). The mean total alkaline phosphatase decreased from 274 to 232 IU L−1 in the calcitriol group and increased from 547 to 669 IU L−1 in the placebo group (P=0.002). The mean bone-specific alkaline phosphatase decreased from 72.5 to 68 μg L−1 in the calcitriol group and increased from 105.3 to 148.5 μg L−1 in the placebo group (P=0.03). The incidence of two consecutive occurrences of elevated calcium×phosphorus (Ca×P>75 mg2 dL−2) product was higher in the calcitriol group than in the placebo group (P=0.01). Two consecutive occurrences of phosphorus >6.5 mg dL−1 occurred in 71% of the calcitriol group and 46% of the placebo group (P=0.14). Calcium levels >10.5 mg dL−1 were more common in the calcitriol group than in the placebo group (P=0.01). There was a direct relationship between serum phosphorus concentration and the percentage change in PTH from baseline in both the calcitriol group (r=0.46; P<0.0001) and the placebo group (r=0.21; P=0.0005). This study demonstrates that IV calcitriol, at initial doses of 0.5–1.5 μg, effectively reduces PTH levels in pediatric HD patients and that patients should be closely monitored for hyperphosphatemia and elevated Ca×P product.