Calcitriol oral pulse therapy in children with renal osteodystrophy (original) (raw)
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The Journal of Pediatrics, 1987
Renal osteodystrophy is a common and incapacitating complication of chronic renal failure in children. Standard therapy with oral calcium supplements, phosphate binders, and vitamin D preparations is often inadequate to control progressive bone disease. We report the use of parenteral calcitriol therapy in two children, aged 2 and 15 years, respectively, with chronic renal failure. This treatment effectively suppressed secondary hyperparathyroidism in both patients, causing a nearly 50% reduction in circulating parathyroid hormone level and a parallel decline in serum alkaline phosphatase activity. In the younger patient, therapy was associated with healing of subperiosteal bone resorption and accelerated growth velocity. These findings indicate that parenteral administration of calcitriol may be an effective treatment option in some patients with refractory renal osteodystrophy and secondary hyperparathyroidism.
“High–dose” calcitriol for control of renal osteodystrophy in children on CAPD
Kidney International, 1987
"High-dose" calcitriol for control of renal osteodystrophy in children on CAPD. High doses of calcitriol were used prospectively for 11 to 29 months to raise serum calcium levels in an effort to control renal osteodystrophy in 16 children undergoing CAPD. Serum Ca, P, iPTH and alkaline phosphatase were measured monthly; hand radiographs were obtained every six months, and a semiquantitative score of bone abnormalities was evaluated by two independent observers. During the study, serum Ca increased from 9.9 0.9 to 11.0 0.6 mgldl (P < 0.001); serum iPTH decreased by 113 131 dEq/ml (P < 0.005); serum P was unchanged; and serum alkaline phosphatase fell by 33 46% (P < 0.02), 530 397 to 204 551 lU/liter. The radiographic score fell from 4.8 4.6 to 0.9 1.2 (P <0.005). The average and maximal doses of calcitriol were 0.61 0.37 and 0.95 0.56 fLg/day or 28 18 and 46 28 ng/kg body wt/day, respectively. Transient and asymptomatic hypercalcemia occurred in nine patients and two patients had reversible conjunctivitis in association with the hypercalcemia. Thus, "high dose" calcitriol prevented or controlled progression of hyperparathyroid bone disease in most pediatric CAPD patients. The failure to suppress PTH or reverse secondary hyperparathyroidism until the serum Ca rose to 10.5 to 11.0 mg/dl could reflect an increase in the "set point" for PTH suppression by serum calcium in many uremic children.
Intravenous calcitriol for treatment of hyperparathyroidism in children on hemodialysis
Pediatric Nephrology, 2005
This double-blind, placebo-controlled study evaluated the safety and efficacy of intravenous (IV) calcitriol (Calcijex) for treatment of secondary hyperparathyroidism (2HPT) 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 calciumphosphorus product values 70 mg 2 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 mg) were based on the severity of 2ºHPT. The dose was increased every two weeks by 0.25 mg until there was at least a 30% decrease in PTH from baseline, or Ca>11.0 mg dL 1 , or CaP>75 mg 2 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 mg L 1 in the calcitriol group and increased from 105.3 to 148.5 mg L 1 in the placebo group (P=0.03). The incidence of two consecutive occurrences of elevated calciumphosphorus (CaP>75 mg 2 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 mg, effectively reduces PTH levels in pediatric HD patients and that patients should be closely monitored for hyperphosphatemia and elevated CaP product.
International Urology and Nephrology, 2000
Objectives: In this prospective study, the effect of calcitriol therapy on bone mineral density and osteopenia in patients with severe secondary hyperparathyroidism has been investigated. Materials and methods: The study was carried out on 24 chronic dialysis patients consisting of 13 boys and 11 girls, aged between 8-18 years. Patients were divided into 3 groups according to the severity of hyperparathyroidism and therapy regimens. Group I consisted of 5 patients with normal parathormon levels who did not receive calcitriol therapy. In group II and III, there were patients with secondary hyperparathyroidism. Group II consisted of 10 patients receiving oral calcitriol therapy. Group III consisted of 9 patients receiving intravenous (IV) calcitriol. Bone mineral density was measured by dual energy x-ray absorptiometry. Osteopenia was defined as a Z-score worse than −2. Bone mineral density was assessed as baseline and at the end of one year. Results: A significant improvement was observed in Z-score in the group III whereas the mean value of Z-score tended to be worse in group I and it was not significantly different in group II from the initial values. The better Z-score in group III was associated with more effective stabilization of alkaline phosphatase level and bone specific alkaline phosphatases (BAP) concentrations. Conclusion: Significant improvement of Z-score in group III suggested the beneficial role in IV administration of calcitriol in chronic dialysis patients.
Pediatric Nephrology, 2006
Childhood renal osteodystrophy (ROD) is the consequence of disturbances of the calcium-regulating hormones vitamin D and parathyroid hormone (PTH) as well as of the somatotroph hormone axis associated with local modulation of bone and growth cartilage function. The resulting growth retardation and the potentially rapid onset of ROD in children are different from ROD in adults. The biochemical changes of ROD as well as its prevention and treatment affect calcium and phosphorus homeostasis and are directly associated with the development of cardiovascular disease in pediatric renal patients. The aims of the clinical and biochemical surveillance of pediatric patients with CRF or on dialysis are prevention of hyperphosphatemia, avoidance of hypercalcemia and keeping the calcium phosphorus product below 5 mmol 2 /l 2 . The PTH levels should be within the normal range in chronic renal failure (CRF) and up to 2-3 times the upper limit of normal levels in dialysed children. Prevention of ROD is expected to result in improved growth and less vascular calcification.
Low-dose intravenous calcitriol treatment of secondary hyperparathyroidism in hemodialysis patients
Kidney International, 1992
Low-dose intravenous calcitriol treatment of secondary hyperparathy. roidism in hemodialysis patients. Intravenous calcitriol is known to directly suppress P1'H secretion and release. We evaluated the effect of four months of treatment with low-dose intravenous calcitriol on PTH levels in 83 hemodialysis patients. The criteria for including patients in the study were a serum P'FH levels at least four times the normal limit, a serum total calcium less than 10 mg/dl and good control of the serum phosphorus level. All patients underwent standard bicarbonate or acetate dialysis; dialysate calcium level was maintained at the usual 3.5 mEq/liter concentration. Initial calcitriol dose was 0.87 0.02 (5EM) .tg (0.015 jzg/kg body wt) thrice weekly at the end of dialysis, and it was reduced in case of hypercalcemia or elevated calcium-phosphate product. Seven out of 83 patients dropped out during treatment. Among the 76 patients who completed the study, 58 (76%) showed a highly significant decrease of intact PTH levels (average reduction 48%) and of alkaline phosphatase levels after four months of therapy. Total serum calcium increased slightly but significantly in the responder group but remained unchanged in the non-responders. No significant changes in ionized calcium levels could be detected, even in responders. Treatment was well tolerated by patients, but 60% of them had transient episodes of hyperphosphatemia. Mean serum phosphate was 4.95 mg/dl at the beginning of the study. It increased significantly after four months of treatment in patients who showed a decrease of PTH levels, although it remained within acceptable limits, below 5.5 mg/dl. Twenty-eight of 76 patients (37%) reduced the dose of calcitriol because their calciumphosphate products exceeded 60. Low-dose intravenous calcitriol therapy for secondary hyperparathyroidism in dialysis patients is safe and may be highly effective in reducing serum PTH and alkaline phosphatase levels without significant increases of ionized calcium concentrations. However, the frequent occurrence of asymptomatic hyperphosphatemia indicates that similar precautions are needed for intravenous and oral calcitriol administration. After the discovery that the kidney is the major organ responsible for the generation of calcitriol, the active form of vitamin D [I], the treatment of renal osteodystrophy has been greatly improved by the introduction in the clinical practice of calcitriol itself and of its analogue, l-a-hydroxyvitamin D [2, 3]. Symptomatic patients affected by secondary hyperparathyroid
Paricalcitol versus calcitriol treatment for hyperparathyroidism in pediatric hemodialysis patients
Pediatric Nephrology, 2006
Secondary hyperparathyroidism (SHPT) remains a treatment dilemma in pediatric dialysis patients. Recent experience with paricalcitol (P), a vitamin D analogue, in adults with SHPT has shown equal efficacy and improved survival compared to traditional treatment with calcitriol (C). We present our experience with (C) compared to (P) treatment in our pediatric dialysis patients with SHPT. Twenty-one patients (mean age 11.5±5 years) with SHPT (intact parathyroid hormone (iPTH) averaging 1,228± 496 pg/ml) were studied. Seventeen received (C) followed by (P); while an additional four were treated with either (C=1) or (P=3) alone. After 26±8 weeks, average percent (%) decrease in iPTH was similar with (C) and (P) (−60.4±34% versus −65.4±28%, respectively; p=0.6). In the (P) group, the effective dose in children was greater than in adult trials based on kilogram weight. Episodes of hypercalcemia between the treatment groups were not different. However, episodes of elevated calcium × phosphorus product (Ca×P)≥70 mg 2 /dl 2 occurred more frequently in the (C) group (odds ratio=1.5; p=0.01). Paricalcitol appears to be safe and effective in pediatric patients. Data suggest that dosing should be gauged according to degree of SHPT. This should serve as impetus for future pharmacokinetic studies in pediatric dialysis patients.
Renal osteodystrophy in pediatric patients on peritoneal dialysis
Advances in peritoneal dialysis. Conference on Peritoneal Dialysis, 2004
Renal osteodystrophy (ROD) is one of the mostfrequent complications in pediatric uremic patients on peritoneal dialysis (PD), and each case requires a different therapeutic approach. In the present study, we characterized ROD in pediatric patients on chronic PD. We studied 20 patients (12 boys, 8 girls) for a 12-month period. The mean age of the patients was 5.82 +/- 5 years. We allocated each patient to one of three groups according to intact parathormone (iPTH) value: group 1, iPTH < or = 150 pg/mL, n = 12; group 2, iPTH 151 - 400 pg/mL, n = 2; and group 3, iPTH > or = 401 pg/mL, n = 6. Monthly, we recorded plasma calcium, phosphorus, and alkaline phosphatase; Kt/V; normalized protein equivalent of total nitrogen appearance (nPNA); and calcitriol dose. Growth was registered as the Z height/age. Student t-test and analysis of variance for repeated measures were used for the statistical analyses. A value of p < 0.05 was considered significant. All 20 patients completed 6 mo...