Paricalcitol versus calcitriol treatment for hyperparathyroidism in pediatric hemodialysis patients (original) (raw)

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.

Intravenous Paricalcitol for Treatment of Secondary Hyperparathyroidism in Children on Hemodialysis

American Journal of Kidney Diseases, 2007

Secondary hyperparathyroidism is a common complication in children receiving hemodialysis. Active vitamin D is an effective therapy, but its use is often limited by hypercalcemia and increased calcium × phosphorus (Ca × P) product. Paricalcitol, a selective vitamin D receptor activator, causes less sustained hypercalcemia and increase in Ca × P product than calcitriol and has been used effectively in adult hemodialysis patients.Double blind, placebo-controlled.Hemodialysis units and pediatric subjects receiving hemodialysis.After a washout period of 2 to 6 weeks, 29 subjects aged 5 to 19 years received either paricalcitol or placebo for up to 12 weeks (0.04 μg/kg if initial intact parathyroid hormone [iPTH] level < 500 pg/mL [ng/L]; 0.08 μg/kg if initial iPTH level > 500 pg/mL [ng/L]). The dose was increased by 0.04 μg/kg every 2 weeks until there was a 30% decrease in iPTH level from baseline or calcium level greater than 11 mg/dL (>2.74 mmol/L) or Ca × P product greater than 75 mg2/dL2 (>6.04 mmol2/L2).Two consecutive 30% decreases from baseline in iPTH levels and safety of paricalcitol, including hypercalcemia and increase in Ca × P product.60% of the paricalcitol group had 2 consecutive 30% decreases from baseline iPTH levels compared with 21% in the placebo group (P = 0.06). The paricalcitol group had a mean decrease in iPTH level of 164 pg/mL (ng/L), whereas the placebo group had a mean increase of 238 pg/mL (ng/L; P = 0.03). There was no difference from baseline to final visit in calcium, phosphorus, or Ca × P product values in either group.Low power to detect differences in safety between groups and a short-term study.Paricalcitol decreased iPTH levels in children receiving hemodialysis with no significant changes in serum calcium, phosphorus, or Ca × P product values during the course of the study.

Cinacalcet is efficacious in pediatric dialysis patients

Pediatric Nephrology, 2008

Secondary hyperparathyroidism (high-turnover bone disease, or HTBD) is manifested by elevated parathyroid hormone (PTH) levels. Control of HTBD may be achieved by maintaining low serum phosphorous levels and administering vitamin D therapy, although some patients continue to exhibit high PTH levels. We report the results of the efficacy of the calcimimetic cinacalcet in six hemodialysis (HD) and three peritoneal dialysis (PD) pediatric patients with HTBD, age 14.5 ± 1.0 (range 7.5–17.5) years. Six patients received 30 mg/day, one required 60 mg/day, and two received 120 mg/day. Treatment with cinacalcet resulted in a 61% decline in intact PTH (iPTH) levels (1,070 ± 171.5 pretreatment to 417.6 ± 97.8 posttreatment pg/ml, p = 0.005). Serum alkaline phosphatase also declined (561.8 ± 169.6 U/L pretreatment to 390.3 ± 110.3 U/L posttreatment pg/ml). During therapy, serum calcium (p = 0.9) and phosphorous (p = 0.9) levels, calcium-phosphorous product (p = 0.8), systolic blood pressure (BP) (p = 1.0), diastolic BP (p = 0.8), and hemoglobin (p = 0.9) remained unchanged. The dose of oral calcitriol for the three patients on PD while receiving cinacalcet trended downward (0.8 ± 0.2 pretreatment vs. 0.5 ± 0.0 μg/day posttreatment pg/ml), as did the dose of paracalcitol for those receiving HD (6.6 ± 2.3 pretreatment vs. 4.3 ± 1.7 micrograms/day posttreatment pg/ml). We conclude that short-term treatment with the calcimimetic cinacalcet is efficacious in adolescent dialysis patients.

Oral paricalcitol: expanding therapeutic options for pediatric chronic kidney disease patients

Pediatric Nephrology

The complex pathophysiology of progressive chronic kidney disease (CKD) and the development of mineral and bone disorder, abbreviated as CKD-MBD, is of vital importance to a pediatric patient. Paricalcitol, the 19 nor-1,25(OH) 2 D 2 analogue was shown to be effective and safe in the treatment of secondary hyperparathyroidism (SHPT) in adults almost two decades ago. It also significantly improved survival in dialysis patients compared to the standard calcitriol. The successful treatment of CKD-MBD in children is essential if they are to grow and survive into adulthood. It can be argued that it is more important for children with CKD than adults since they have early and prolonged disease risk exposure. In this issue of Pediatric Nephrology, Webb et.al. report a dual trial of the safety, efficacy, and pharmacokinetics of paricalcitol in children aged 10-16 years with moderate but significant efficacy in meeting the endpoint of >30% decrease in parathyroid hormone (PTH) levels from baseline with minimal adverse events. Much more research needs to be done to expand and develop clinical pharmaceutical trials in the use of paricalcitol in children, especially in the younger age categories. This current study has done much to open the doors for future studies, with the caveat that it has been long coming and much more needs to be done to compensate for this delay in the treatment of children with CKD-MBD and cardiovascular and renal disease progression.

Hypoparathyroidism versus hyperparathyroidism in pediatric dialysis patients; a single center study

Journal of Nephropathology, 2017

Background: Abnormalities in calcium, phosphorous and parathyroid hormone (PTH) metabolisms are common in dialysis patients. Reaching target levels for these serologic factors and calcium × phosphorous products is recommended to minimize cardiovascular events. Objectives: The aim of this study was to examine calcium, phosphorous and intact PTH (iPTH) abnormalities in a group of dialysis patients. Patients and Methods: Bone minerals status and iPTH levels were assessed in 46 dialysis patients aged 19-300 (165.2 ± 75.73) months. Low and high Ca dialysate solutions routinely were used for hemodialysis (63%) and peritoneal dialysis (30.4%) patients respectively. Comparisons between groups were performed with considering age (≤5, 6-10, and > 10 years), gender and modality of dialysis. Results: Serum calcium and corrected calcium levels were significantly higher in peritoneal dialysis (PD) patients. Hypoparathyroidism was the most frequent iPTH abnormality (58.7%). It was more prevalent in males. Hyperparathyroidism was more frequent in females. Conclusions: We found that hypoparathyroidism is the most prevalent PTH abnormality. We also noted that patients on peritoneal dialysis are more prone to develop this form of PTH abnormality. We found that phosphate control is better in peritoneal dialysis vs. hemodialysis cases.

Recent advances in pediatric dialysis: a review of selected articles

Pediatric Nephrology, 2008

Important discoveries and studies that help inform us about the best methods to evaluate and manage children with end-stage renal disease (ESRD) continue to emerge. This review addresses a number of recent publications regarding important clinical issues for children with ESRD. Despite advances made in previous years, many clinical problems remain in the care of the pediatric dialysis patient. This review covers five topics of recent interest: three articles that address important patient outcome measures such as dialysis adequacy and hemoglobin; two articles that address growth failure in a chronic dialysis patients; five articles that address cardiovascular (CV) morbidity, mortality, and interventions to reduce CV risk in children; two articles that address mineral-bone disorder (MBD) and evidence that past strategies for MBD in children may have increased CV disease; and two articles that address nephrogenic systemic fibrosis, a recently described disorder in chronic kidney disease (CKD) patients that occurs in children as well as adults. Using a concise consistent format, each of the 14 key publications is summarized, and the "conclusion" for the practitioner is identified.

Chronic kidney disease and secondary hyperparathyroidism in children

Journal of Parathyroid Disease, 2015

Introduction Chronic kidney disease (CKD), a significant health problem with many adverse complications, affects approximately 14.5% of US population (1). In the past two decades the incidence of renal failure is not only rising among adults but also in children (2). CKD is defined as "evidence of structural or functional kidney abnormalities (abnormal urinalysis, imaging studies or histology), that persists for at least three months, with or without a decreased glomerular filtration rate (GFR), as defined by a GFR of less than 60 ml/min per 1.73 m 2 , by KDIGO (2). Some adverse effects of CKD may act as progressive factors to end-stage renal failure (ESRD). Among these factors, osteodystrophy, systemic and intraglomerular hypertension, glomerular hypertrophy, proteinuria, tubulointerstitial disease are remarkable (2). Secondary hyperparathyroidism is a well-known independent risk factor of developing bone disease, vascular calcification, and all-cause mortality and morbidity even in non-CKD patients (3-6). Although most guidelines recommend prescription of vitamin D analogs in pre-dialysis CKD patients, there is no consensus on dose, time of prescription, type of analog (D2 or D3) and duration of prescription of vitamin D. Vitamin D analogs, preparations, prescription, doses and intervals Keeping optimal bone turnover needs using vitamin D analog from early stages of CKD (stage 3) (1). KDOQI and kidney disease improving global outcomes (KDIGO) recommend either D2 or D3 analog interchangeably in pre-dialysis stages (7). Vitamin D derivatives (vitamin D receptor activators; VDRAs) are divided into two groups (8): a) Non-selective and agonist activators (VDRAs) b) Selective VDRAs Non-selective VDRAs are most popular and include; calcitriol (1α,25(OH)2D3), alfacalcidol(1α,25(OH)D3) and doxercalciferol(1α,25OHD2). Most studies on administrating non-selective VDRAs and ergocalciferol support the effectiveness of these compounds on secondary hyperparathyroidism (SHPT) in early stages of CKD (9-14). Regarding the results of Implication for health policy/practice/research/ medical education Secondary hyperparathyroidism is a well-known independent risk factor of developing bone disease, vascular calcification, and all-cause mortality and morbidity even in end-stage renal disease (ESRD) patients and patients under hemodialysis.

Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease

Pediatric Nephrology, 2017

Background Elevated intact parathyroid hormone (iPTH) levels can contribute to morbidity and mortality in children with chronic kidney disease (CKD). We evaluated the pharmacokinetics, efficacy, and safety of oral paricalcitol in reducing iPTH levels in children with stages 3-5 CKD. Methods Children aged 10-16 years with stages 3-5 CKD were enrolled in two phase 3 studies. The stage 3/4 CKD study characterized paricalcitol pharmacokinetics and compared the efficacy and safety of paricalcitol with placebo followed by an open-label period. The stage 5 CKD study evaluated the efficacy and safety of paricalcitol (no comparator) in children with stage 5 CKD undergoing dialysis. Results In the stage 3/4 CKD study, mean peak plasma concentration and area under the time curve from zero to infinity were 0.13 ng/mL and 2.87 ng•h/((or ng×h/))mL, respectively, for 12 children who received 3 μg paricalcitol. Thirty-six children were randomized to paricalcitol or placebo; 27.8% of the paricalcitol group achieved two consecutive iPTH reductions of ≥30% from baseline versus none of the placebo group (P = 0.045). Adverse events were higher in children who received placebo than in those administered paricalcitol during the double-blind treatment (88.9 vs. 38.9%; P = 0.005). In the stage 5 CKD study, eight children (61.5%) had two consecutive iPTH reductions of ≥30% from baseline, and five (38.5%) had two consecutive iPTH values of between 150 and 300 pg/ mL. Clinically meaningful hypercalcemia occurred in 21% of children. Conclusions Oral paricalcitol in children aged 10-16 years with stages 3-5 CKD reduced iPTH levels and the treatment was well tolerated. Results support an initiating dose of 1 μg paricalcitol 3 times weekly in children aged 10-16 years.

The importance of dosing intravenous calcitriol in dialysis patients with severe hyperparathyroidism

American Journal of Kidney Diseases, 1995

0 The current study evaluates the use of intravenous (IV) calcitriol in 10 patients with severe hyperparathyroidism (HPTH). Patients with parathyroid hormone (PTH) >1,2W pg/m and serum P < 0.5 mg/dL were studied. Ten patients with a mean PTH of 1,823 2 148 pg/mL were treated for a mean of 48 weeks with a dose of IV calcitriol commensurate to the level of PTH. The initial calcltrlol dose had to be increased in seven patients. The mean maximum dose of calcittiol was 3.8 pg thrice weekly. There was a dramatic decrease in PTH levels, and by the end of the study it was 211 +-48 pg/mL Alkaline phosphatase decreased from 582 2 3 to 120 + 12 IU/L Serum Ca and P remained unchanged in most patients. There were three episodes of hyperphosphatemia in one patient, and another had a hypercalcemic episode. In conclusion, patients with severe HPTH respond very well to Iv calcitriol, provided that dosing of calcitrlol is commensurate to PTH levels, and hyperphosphatemia is kept under control. 0 1995 by the National Kidney Foundation, Inc.

An open-label study to evaluate a single-dose of cinacalcet in pediatric dialysis subjects

Pediatric Nephrology, 2012

Background There is limited knowledge of the effectiveness and safety profile of cinacalcet in pediatric patients with secondary hyperparathyroidism (sHPT) treated with dialysis. Methods This was an open-label, single-dose study conducted on 12 pediatric subjects with chronic kidney disease treated with dialysis. Subjects were stratified by four age cohorts and given a single 15-mg oral dose of cinacalcet. Multiple blood samples were collected up to 72 h post-dose for the assessment of serum calcium (Ca), serum intact parathyroid hormone (iPTH), and plasma cinacalcet concentrations. Results Overall, cinacalcet was well tolerated with no serious adverse events. Mean (standard deviation) percentage change in serum Ca over the first 12 h post-dose was −2.93 % (5.70 %) with a nadir of −4.34 % (6.04 %) at 8 h; Ca values returned to baseline by 48 h post-dose. Mean percentage change in iPTH over the first 12 h post-dose was 57.94 % (71.82 %) with a nadir of −35.65 % (55.82 %) at 2 h. There was an inverse relationship between peak serum Ca concentration and body surface area (BSA) (r 2 00.41), although no relationship was found between area under the curve and age or BSA. Conclusions These data support future analysis to determine the therapeutic starting dose of cinacalcet for pediatric patients with sHPT on dialysis.