Intravenous calcitriol for treatment of hyperparathyroidism in children on hemodialysis.
This double-blind, placebo-controlled study evaluated the safety and efficacy of intravenous (i.v.) calcitriol (Calcijex) for treatment of secondary hyperparathyroidism (secondary 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 < or = 10.5 mg dL(-1) and calcium x phosphorus product values < or = 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 microg) were based on the severity of secondary HPT. The dose was increased every two weeks by 0.25 microg until there was at least a 30% decrease in PTH from baseline, or Ca > 11.0 mg dL(-1), or Ca x P > 75 mg2 dL(-2). Overall, 11/21 (52%) patients in the calcitriol group had two consecutive > or = 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 microg L(-1) in the calcitriol group and increased from 105.3 to 148.5 microg L(-1) in the placebo group (P=0.03). The incidence of two consecutive occurrences of elevated calcium x phosphorus (Ca x 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 i.v. calcitriol, at initial doses of 0.5-1.5 microg, effectively reduces PTH levels in pediatric HD patients and that patients should be closely monitored for hyperphosphatemia and elevated Ca x P product.
Greenbaum
Larry A
LA
Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA. lgreen@mcw.edu
Grenda
Ryszard
R
Qiu
Ping
P
Restaino
Irene
I
Wojtak
Amy
A
Paredes
Ana
A
Benador
Nadine
N
Melnick
Joel Z
JZ
Williams
Laura A
LA
Salusky
Isidro B
IB
D000085:Acetates / Q000008:administration & dosage; D000293:Adolescent; D002117:Calcitriol / Q000008:administration & dosage* / Q000009:adverse effects; D002118:Calcium / Q000097:blood; D002119:Calcium Carbonate / Q000008:administration & dosage; D002120:Calcium Channel Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D017610:Calcium Compounds; D002648:Child; D002675:Child, Preschool; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000188:drug therapy / Q000209:etiology; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood; D006435:Renal Dialysis
D000085:Acetates; D002120:Calcium Channel Agonists; D017610:Calcium Compounds; D010281:Parathyroid Hormone; D010710:Phosphates; D002117:Calcitriol; D002119:Calcium Carbonate; D002118:Calcium; C120662:calcium acetate