Cinacalcet is efficacious in pediatric dialysis patients (original) (raw)
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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.
Short- and middle-term continuous use of cinacalcet in children on peritoneal dialysis
Journal of Pediatric Endocrinology and Metabolism, 2013
Background: Secondary hyperparathyroidism (HPT) constitute a high-turnover bone disease, manifested by elevated parathyroid hormone. Cinacalcet, belonging to calcimimetics, has been shown to be promising in the control of secondary HPT with limited data in children. Objective: To evaluate the safety and efficacy of cinacalcet in children on peritoneal dialysis (PD) with secondary HPT. Methods: Four patients on PD with severe secondary HPT, uncontrolled with phosphorus dietary restrictions combined with phosphate binders and analog of 1,25 vitamin D 3 received cinacalcet. Results: After cinacalcet treatment, in two of four patients, we found a serum intact parathyroid hormone (iPTH) level reduction by more than 70 % at 4 weeks and more than 60 % at 3 or more than 6 months. Nevertheless, in the other two patients, a transient reduction of iPTH was found in 4 weeks and an increase in 3 or more months, who were finally treated with surgical parathyroidectomy. During cinacalcet treatment, no adverse events were noted. Conclusion: Cinacalcet may be a safe and effective treatment for PD patients with secondary HPT, although surgical parathyroidectomy cannot be avoided in certain cases.
Nutrients, 2013
Aim: Uremic hyperparathyroidism (UHPT) has been shown to contribute to the development and progression of chronic kidney disease-mineral bone disorder. UHPT is frequently observed in chronic dialysis patients, and patients with UHPT are associated with increased risk of all-cause and cardiovascular mortality. Cinacalcet is a novel agent that increases sensitivity to the calcium-sensing receptor and is approved for control of UHPT. Nevertheless, cinacalcet is costly and information regarding efficacy of low-dose cinacalcet on UHPT is limited. Methods: We conducted a retrospective study to evaluate treatment with either low-dose calcitriol combined with low-dose cinacalcet (25 mg) (D-Cinacalcet) or calcitriol alone (VitD) in dialysis patients with moderate to severe UHPT. A total of 81 dialysis patients were enrolled (40 subjects in D-Cinacalcet group and 41 subjects in VitD group). Demographic data including age, gender, duration on dialysis and biochemical data were reviewed and recorded. Results: At the end of the study, the intact parathyroid hormone (iPTH) levels of the D-Cinacalcet group declined significantly (from 1166.0 ± 469.3 pg/mL to 679.8 ± 421.6 pg/mL, p < 0.0001), while there was no significant change in the VitD group. Significant decrease of serum calcium (Ca: 9.9 ± 0.6 mg/dL vs. 9.6 ± 0.8 mg/dL, p = 0.002), phosphorus (P: 5.9 ± 1.3 mg/dL vs.
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.
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.
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
Seminars in Dialysis, 2005
As suggested by its American brand name (Sensipar), the calcimimetic cinacalcet sensitizes the parathyroid cells to the extracellular calcium signal, suppressing parathyroid hormone (PTH) release and synthesis and preventing parathyroid cell proliferation. This primary PTH suppression decreases the release of calcium and phosphate from bone without increasing intestinal absorption of calcium and phosphate. Therefore cinacalcet decreases the risk of hypercalcemia and hyperphosphatemia in contrast to 1α-OH vitamin D derivatives. Compared with calcium-containing oral phosphate binder (OPB), it increases the risk of hypocalcemia and may decrease the PTH-mediated phosphaturia in predialysis patients. This justifies its combined use with calcium-containing OPB in order to prevent hypocalcemia and enhance the hypophosphatemic effect of the latter, while improving PTH suppression. The National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) has recommended restriction of supplemental elemental calcium to 1.5 g/day, a recommendation that we believe should be revised. No pathophysiologic or randomized trial data have yet evidenced the absolute necessity for systematically using 1α-OH vitamin D derivatives and noncalcium-containing OPB rather than higher doses of calcium-containing OPB alone in uremic patients without vitamin D insufficiency. In patients with hyperparathyroidism as severe as in the “Treat to Goal Study,” the Durham study showed that a calcium carbonate dose more than three times the K/DOQI limit could decrease PTH into the recommended range, with the advantage of a lower calcium-phosphate product compared with the combination of calcitriol and noncalcium OPB. Besides the efficient PTH suppression associated with lower calcium-phosphate product and a good gastrointestinal tolerance, long-term data suggest that cinacalcet may decrease the risk of parathyroidectomy and fracture, while high bone turnover lesions are improved. However, no long-term data on bone mineral density and cardiovascular calcification and complications are yet available. Such studies, along with those comparing cinacalcet and 1α-OH vitamin D-based approaches to hyperparathyroidism, are needed.
Nephrology Dialysis Transplantation, 2007
Background. The purpose of the present study was to evaluate the impact of cinacalcet administration on the attainment of Kidney Disease Outcomes Quality Initiative of the National Kidney Foundation (NFK-K/DOQI) targets, in a group of dialysis patients with secondary hyperparathyroidism that were not controlled with vitamin D metabolites due to inadequate elevations in serum calcium and/or phosphorus. Methods. Twenty-eight patients undergoing haemodialysis that presented secondary hyperparathyroidism (PTH > 300 pg/ml) with difficulty to use vitamin D either because of hypercalcaemia (>10.2 mg/dl) and/or hyperphosphoraemia (>5.5 mg/dl) were included in this study. The follow-up period was 9 months before and after the introduction of cinacalcet. We started by adding 30 mg of cinacalcet orally once daily to their previous vitamin D metabolite treatment. The following variables were calculated and recorded: the mean of all measurements of serum Ca, P and parathyroid hormones (PTH), and Ca  P in each patient; calcium in dialysate (mEq/l); doses of vitamin D administered; doses of cinacalcet used, and the average prescription of calcium-based phosphate binders, sevelamer hydrochloride and aluminum binders, corresponding to two periods according to the introduction of cinacalcet. The proportions of patients with different serum Ca levels as well as serum P levels; serum PTH levels and CaxP at the beginning and at the end of the nine month period of treatment with cinacalcet were calculated. Results. Serum PTH (826.9 AE 325 vs 248.1 AE 77.3, P < 0.001), serum calcium (9.9 AE 0.6 vs 8.6 AE 0.4, P < 0.001) and the Ca  P product (94.7 AE 7.3 vs 43.6 AE 8.5; P < 0.001) diminished significantly whereas serum phosphorus remained unchanged (4.8 AE 1.5 vs 4.3 AE 1.1; P ¼ NS). Before cinacalcet, 23 patients had severe hyperparathiroidism (serum PTH > 500) and 15 patients hypercalcaemia (serum calcium >10.2 mg/dl). After 9 months of treatment, all 28 patients showed serum PTH < 500 pg/ml and serum calcium <10.2 mg/dl; 64.7% of the patients achieved Ca, P, Ca  P and PTH objectives simultaneously. While the mean dose of cinacalcet increased along the 9 months of treatment (P < 0.001), there were no significant changes in vitamin D metabolites (P ¼ 0.5), neither in the mean doses of calciumcontaining agents, nor in the mean prescribed doses of sevelamer (P < 0.01), and aluminium-containing agents diminished significantly (P < 0.05). Conclusions. In summary, the combination of cinacalcet and low doses of vitamin D improved significantly the control of PTH and Ca  P in patients with severe secondary hyperparathiroidism on chronic haemodialysis, without adverse effects and with lower doses of phosphate binders.
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.