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1.
Safety and efficacy of pulse and daily calcitriol in patients on CAPD: a randomized trial 总被引:2,自引:1,他引:1
Moe S; Kraus M; Gassensmith C; Fineberg N; Gannon F; Peacock M 《Nephrology, dialysis, transplantation》1998,13(5):1234-1241
Background: Calcitriol therapy is the mainstay of
therapy for the treatment of secondary hyperparathyroidism. Oral
administration of calcitriol is necessary in CAPD patients, but no studies
have directly compared different routes of administration in this patient
population. Methods: To determine if the peak serum
calcitriol level (pulse therapy) is more important than the total delivered
dose, we randomized CAPD patients with mild to moderate secondary
hyperparathyroidism to receive either pulse (3.0 &mgr;g twice a week,
n=10) or daily (0.75 &mgr;g a day, n=8) oral calcitriol in comparable
weekly doses. The main comparison was the rate of decline of serum intact
parathyroid hormone (PTH) levels to reach the desired end-point of 100
pg/ml. The patients were dialysed with low-calcium dialysate and received
only calcium-containing phosphate binders. Results:
Pharmacokinetic analysis after a single dose of 3.0 &mgr;g (pulse)
vs 0.75 &mgr;g (daily) revealed 1,25(OH)2-vitamin
D levels to be higher in the pulse group at 3 and 6 h, but equivalent by 12
h. The area under the curve for 1 week of daily and 1 week of pulse therapy
was equal. The patients in the 2 arms had equivalent basal serum levels of
PTH (pulse=562±291 vs
daily=454±113 pg/ml), calcium (pulse=2.32±0.20
vs daily=2.32±0.12 mmol/l) and phosphorus
(pulse=1.32±0.52 vs
daily=1.35±0.26 mmol/l). The time required for the PTH to
decrease to 100 pg/ml and rate of decline in PTH were similar (time:
pulse=14.2±6.8 weeks, daily=12.2±7 weeks; rate:
pulse=7.4±4.2 vs daily=8.4±4.2%
PTH/week; P=NS). The serum calcium increased similarly in both groups.
Hypercalcaemia (>2.9 mmol/l) was rare (pulse=3, daily=2 episodes).
Conclusions: This study demonstrates that pulse and
daily calcitriol are similarly effective and safe for the treatment of mild
to moderate secondary hyperparathyroidism in CAPD patients despite higher
peak levels of 1,25(OH)2-vitamin D with pulse therapy. Key
words: calcitriol; calcium balance; CAPD; dialysis;
hyperparathyroidism; renal osteodystrophy
相似文献
2.
BACKGROUND: Secondary hyperparathyroidism, a major clinical problem in patients with chronic renal failure, develops in response to phosphate retention and impaired calcitriol [1,25-dihydroxyvitamin D3] synthesis. Vitamin D therapy, particularly alfacalcidol [1 alpha-hydroxyvitamin D3], has been shown to be effective in the treatment of secondary hyperparathyroidism. The aim of this study was to compare the effect of a 12-week course of continuous versus intermittent oral alfacalcidol therapy on parathyroid hormone suppression. PATIENTS AND METHODS: 34 patients were selected and randomly divided into 2 groups to receive either intermittent or continuous oral alfacalcidol. Baseline data were obtained on serum calcium, phosphorus, alkaline phosphatase and PTH. All but the PTH were monitored monthly. PTH levels were measured again until the end of the protocol. The intervention was 2 microg of alfacalcidol given after each dialysis session (intermittent group) or 1 microg given 6 days/week (continuous group). RESULTS: Serum calcium and phosphorus showed a tendency to increase from baseline levels in both groups. Mean PTH levels for both groups showed a progressive reduction over time during the study period. This decrement showed no significant difference with regard to the schedule of alfacalcidol administration when comparing the 2 groups. There also was no difference in the incidence of side effects--hypercalcemia and hyperphosphatemia--between the intermittent and continuous intervention. CONCLUSION: Feedback regulation of PTH with oral alfacalcidol therapy is efficient in the treatment of hyperparathyroidism. However, intermittent and continuous oral administration are equally effective in suppressing an elevated PTH level in hemodialysis patients, with similar safety margins. 相似文献
3.
Tamura S Ueki K Mashimo K Tsukada Y Naitoh M Abe Y Kawai H Tsuchida A Wakamatsu R Nojima Y 《Clinical and experimental nephrology》2005,9(3):238-243
Background 1,25-dihydroxy-22-ovavitamin D3 (22-oxacalcitriol, OCT) was recently introduced commercially as an analogue of 1,25 (OH)2 vitamin D3, but one which has less pronounced calcemic activity.
Methods To examine the efficacy and tolerability of OCT, 46 hemodialysis patients with secondary hyperparathyroidism were randomly
assigned to receive either intravenous OCT or oral calcitriol pulse therapies. The patients were monitored for serum calcium,
phosphate, intact parathyroid hormone (PTH), and bone alkaline phosphatase (BAP) for 24 weeks. The efficacy of intravenous
OCT was also examined in 24 additional patients who were refractory to oral calcitriol pulse therapy.
Results In the randomized trial, intact PTH levels were significantly suppressed within 4 weeks after the initiation of each therapy,
and this effect was well maintained thereafter in both treatment groups. While intact PTH was significantly lower at 4 weeks
in the calcitriol pulse group than in the OCT group (P = 0.02), no statistical differences were observed during later treatment periods. BAP was reduced equally by each treatment.
At 4 weeks (P = 0.02) and thereafter (P = 0.06), serum calcium was higher among calcitriol-treated patients than among those who received OCT treatment. Eight of
24 patients who were refractory to oral calcitriol pulse therapy responded to intravenous OCT. The patients who responded
tended to have lower serum intact PTH and phosphorus levels and smaller parathyroid glands at the start of OCT treatment than
nonresponders.
Conclusions OCT is as effective as oral calcitriol pulse therapy in suppressing intact PTH and BAP in chronic hemodialysis patients. It
was confirmed that OCT exhibits less calcemic activity than calcitriol. Moreover, under certain conditions, switching to OCT
may help in the treatment of hyperparathyroidism, which is refractory to conventional oral calcitriol pulse therapy. 相似文献
4.
Y. Rhee M. Kang Y. Min D. Byun Y. Chung C. Ahn K. Baek J. Mok D. Kim D. Kim H. Kim Y. Kim S. Myoung D. Kim S.-K. Lim 《Osteoporosis international》2006,17(12):1801-1807
Introduction A randomized, double-blind, prospective, 24-week clinical trial was performed to evaluate the effects of a combinative agent, Maxmarvil, of calcitriol (0.5 μg) and alendronate (5 mg) on bone metabolism in postmenopausal women.Methods A total of 217 postmenopausal women with osteoporosis were enrolled; 199 patients were randomly assigned to one of two treatment groups (Maxmarvil group or alfacalcidol group). None of the patients were vitamin-D-deficient, as assessed by serum 25-hydroxyvitamin D (25(OH)D), nor had they received any drugs affecting bone metabolism before enrollment. Bone mineral densities (BMD) of L1–L4 and the femur were measured by dual-energy X-ray absorptiometry (DXA) at the initial assessment and after 6 months of treatment. Serum biochemical assays, including serum calcium, 24-h urinary calcium excretion, and bone turnover markers (both bone-specific alkaline phosphatase [bsALP] and urine N-telopeptide [NTx]), were performed at the baseline and after 3 and 6 months of treatment.Results In the Maxmarvil group, the BMD of the lumbar spine increased up to 2.42±0.5% from the baseline after 6 months (p<0.05). On the other hand, the change in BMD in the alfacalcidol group was 0.28±0.5% after 6 months. There was no significant difference in femoral BMD between the two groups. The levels of bsALP and NTx were significantly lower in the Maxmarvil group than in the alfacalcidol group (−22.04±3.9% vs. −11.42±2.8% [p<0.05] and −25.46±5.2% vs. 1.24±6.2% [p<0.001], respectively). Interestingly, there was a significantly smaller amount of 24-h urinary calcium in the Maxmarvil group (p<0.05).Conclusions Our study demonstrates that a combination of calcitriol and alendronate is quite effective in preventing bone loss, with the advantage of lesser hypercalciuric effect of calcitriol in the postmenopausal osteoporotic women. 相似文献
5.
Martin-Malo A.; Rodriguez M.; Martinez M. E.; Torres A.; Felsenfeld A. J. 《Nephrology, dialysis, transplantation》1996,11(8):1553-1558
BACKGROUND.: Renal failure results in decreased calcitriol production, akey factor in the development of secondary hyperparathyroidism.Phosphorus accumulation and high parathyroid hormone (PTH) levels,both inherent to renal failure, have different effects on calcitriolproduction; moreover, dietary calcium loading may have a separateinhibitory effect on calcitriol production. This study was designedto evaluate the relative effects of PTH and dietary phosphorusand calcium on serum calcitriol levels. METHODS.: Renal failure was surgically induced and rats were divided intonormal, moderate renal failure, and advanced renal failure basedon the serum creatinine. Each group was subdivided and receivedeither a highphosphorusdiet (HPD, 0.6% Ca, 1.2% P) or highcalcium diet (HCaD, 1.2% Ca, 0.6% P) for 1416 days to determinethe relative effects of dietary calcium andphosphorus loadingon serum calcitriol. In addition the effect of PTH and phosphoruson calcitriol stimulation was determined with a 48-h PTH infusioncombined with either a low (0.16%) or high (1%) phosphorus dietsboth diets had negligible calcium (<0.05%) RESULTS.: With decreasing renal function, PTH increased and was greaterin rats fed the HPD than the HCaD; serum calcitriol decreasedas renal function decreased and was lower in normal rats andrats with moderate renal failure fed a HCaD (P < 0.01). Thecalcitriol response to a PTH infusion decreased as renal functiondecreased (P <0.05) but was greater on a low- (0.16%) thana high- (1%) phosphorus diet (P<0.05) CONCLUSION.: Dietary calcium loading either directly decreases serum calcitriolor acts by modifying the stimulatory effect of PTH; the stimulatoryeffect of PTH on serum calcitriol is modified by dietary phosphorus;in moderate renal failure, serum calcitriol levels depend ona complex interaction between PTH and dietary calcium and phosphorus;and in advanced renal failure, serum calcitriol levels are lowand are difficult to stimulate, presumably because of the lossof renal mass. 相似文献
6.
Implications of intermittent calcitriol therapy on growth and secondary hyperparathyroidism 总被引:1,自引:1,他引:0
Secondary hyperparathyroidism is the most common skeletal lesion in pediatric patients undergoing maintenance dialysis. The
present review summarizes a prospective randomized study that evaluated the biochemical and skeletal responses to intermittent
calcitriol therapy in 33 pediatric patients on peritoneal dialysis with secondary hyperparathyroidism. Also, the effect of
intermittent calcitriol therapy on linear growth was evaluated in 16 of 33 patients who had completed the clinical trial.
Serum parathyroid hormone levels decreased by 62% from 648±125 pg/ml in patients treated with intermittent intraperitoneal
(IP) calcitriol, and values remained unchanged from pre-treatment levels of 670±97 pg/ml with oral calcitriol therapy. Overall
serum total and ionized calcium levels were higher in patients treated with IP calcitriol during the study. In contrast to
these biochemical findings, the skeletal lesions of secondary hyperparathyroidism improved after 12 months of treatment in
both groups and adynamic bone occurred in 33% of the patients. Z-scores for height decreased from –1.80±0.3 to –2.00±0.3, P<0.01, after 12 months of intermittent calcitriol therapy. Such findings suggest that an intermittent schedule of calcitriol
administration adversely affects chondrocyte activity within epiphyseal cartilage in pre-pubertal children with end-stage
renal disease.
Received: 20 August 1999 / Revised: 2 February 2000 / Accepted: 9 February 2000 相似文献
7.
Calcium acetate versus calcium carbonate as oral phosphate binder in pediatric and adolescent hemodialysis patients 总被引:3,自引:1,他引:2
Michael Wallot Klaus-Eugen Bonzel Andreas Winter Birgit Geörger Bernhard Letten Martin Bald 《Pediatric nephrology (Berlin, Germany)》1996,10(5):625-630
Calcium carbonate is widely used as an oral phosphorus binder to control hyperphosphatemia in children on maintenance hemodialysis.
Intestinal calcium absorption may induce hypercalcemia, particularly if calcitriol is given simultaneously. In adults, calcium
acetate binds phosphorus more effectively than calcium carbonate, while reducing the frequency of hypercalcemic events. We
therefore compared calcium acetate with calcium carbonate in nine pediatric patients on long-term maintenance hemodialysis.
Following a 1-week withdrawal of phosphorus binders, calcium carbonate was administered for 7 weeks; after a second withdrawal,
calcium acetate was given for another 7 weeks. All patients received calcitriol regularly. Both agents lowered the serum phosphorus
concentration significantly (calcium carbonate 5.7±1.4 vs. 7.7±2.1 mg/dl, P<0.005; calcium acetate 5.8±1.4 vs. 7.8±2.0 mg/dl, P<0.005). Significantly less elementary calcium was ingested with calcium acetate than with calcium carbonate: 750 (375 – 1,500)
vs. 1,200 (0 – 3,000) mg calcium/day, P<0.0001. With calcium carbonate serum calcium increased significantly. The number of episodes of hyperphosphatemia or hypercalcemia
did not differ between treatments. Intact plasma parathyroid hormone (PTH) decreased significantly with both phosphate binders,
and serum 25-hydroxyvitamin D3 increased. There was a close relationship between serum phosphorus and PTH in prepubertal but not in pubertal patients. We
conclude that hyperphosphatemia can be controlled effectively by both calcium acetate and calcium carbonate in pediatric hemodialysis
patients. The oral load of elementary calcium is reduced significantly by binding phosphorus with calcium acetate instead
of calcium carbonate; nevertheless, hypercalcemic episodes remain equally frequent with both phosphate binders.
Received May 9, 1995; received in revised form and accepted February 23, 1996 相似文献
8.
R. M. Francis 《Calcified tissue international》1997,60(1):111-114
There is a decline in serum 25 hydroxyvitamin D (25OHD), 1,25 dihydroxyvitamin D (1,25(OH)2D), and calcium absorption with advancing age, which may lead to secondary hyperparathyroidism and bone loss. Studies show
a relationship between serum 25OHD and bone density in older men and women, with an inverse correlation between bone density
and parathyroid hormone (PTH). Vitamin D supplementation in this age group improves calcium absorption, suppresses PTH, and
decreases bone loss. Vitamin D many also reduce the incidence of hip and other nonvertebral fractures, particularly in the
frail elderly who are likely to have vitamin D deficiency. Patients with established vertebral osteoporosis have lower calcium
absorption than age-matched control subjects, possibly due to reduced serum 1,25(OH)2D or to relative resistance to the action of vitamin D on the bowel. Malabsorption of calcium in women with vertebral crush
fractures does not usually respond to treatment with physiological doses of vitamin D, but can be corrected by pharmacological
doses of vitamin D or by low doses of calcitriol or alfacalcidol. In a recent randomized, controlled study in 46 elderly women
with radiological evidence of vertebral osteoporosis, alfacalcidol 0.25 μg twice daily improved calcium absorption, decreased
serum PTH, and reduced alkaline phosphatase, whereas vitamin D2 500–1000 IU daily had no effect over the 6-month study period. Studies of the effect of the vitamin D metabolites in the
management of elderly women with established vertebral osteoporosis have yielded conflicting results, but suggest that alfacalcidol
and calcitriol may decrease spinal bone loss and reduce the incidence of vertebral fractures. Although vitamin D supplementation
decreases bone loss and fracture risk in the frail elderly, vitamin D metabolites may prove more useful in the treatment of
elderly women with vertebral osteoporosis. 相似文献
9.
Odvina CV Sakhaee K Heller HJ Peterson RD Poindexter JR Padalino PK Pak CY 《Urological research》2007,35(3):123-128
The exact metabolic-physiological background for kidney stone formation in primary hyperparathyroidism (PHPT) is unclear.
To obtain clarification, this retrospective data analysis was conducted in 131 patients with PHPT who had undergone a detailed
ambulatory evaluation on a random diet since 1980. The baseline biochemical presentation of 78 patients with PHPT with stones
was compared with that of 53 patients without stones. Compared to those without stones, the stone-forming patients had a more
marked hypercalciuria (343 ± 148 vs. 273 ± 148 mg/day, P < 0.01). Urinary saturation of calcium oxalate and brushite was significantly higher in stone-formers. Serum PTH and fasting
urinary calcium were similar between the two groups, but serum phosphorus was significantly lower in stone-formers. Serum
calcitriol (available in some patients) showed a slightly higher mean value in stone-formers but the difference was not significant.
The increment in urinary calcium after oral load of 1-g calcium was twofold higher among stone-formers. Radial shaft and L2–L4
bone mineral densities resided within the normal ranges. Stone-formers with PHPT display exaggerated urinary calcium excretion
due to intestinal hyperabsorption of calcium, contributing to a greater enhancement of the saturation of stone-forming calcium
salts. 相似文献
10.
Caravaca F.; Cubero J. J.; Jimenez F.; Lopez J. M.; Aparicio A.; Cid M. C.; Pizarro J. L.; Liso J.; Santos I. 《Nephrology, dialysis, transplantation》1995,10(5):665-670
To assess the effect of the different modes of calcitriol administrationon PTH-ionized calcium relationship we conducted a prospectiveclinical trial in 33 patients on chronic haemodialysis withsecondary hyperparathyroidism (four times upper normal limitintact PTH) who were randomly assigned, with stratificationto PTH levels, to receive daily oral, intermittent oral, orintermittent intravenous calcitriol at the same dose of 0.045µg/kg/weekly. PTH-iCa curves were generated by inducinghypo- or hypercalcaemia in sequential haemodialysis 1 week apart,before and after 10 weeks on treatment. All patients were dialysedagainst a dialysate calcium concentration of 2.5 mEq/l throughoutthe study period. After drop-outs, 26 patients completed the study: 11 on intravenouscalcitriol (mean basal PTH±SD: 666±280 pg/ml),eight on intermittent oral calcitriol (mean basal PTH: 831±361),and seven on daily oral calcitriol (mean basal PTH: 719±280).Serum ionized calcium and phosphorus significantly increasedin intravenous and daily oral groups after calcitriol treatment,but not in the intermittent oral group. Basal PTH did not significantlychange in the three groups after 10 weeks on treatment. MaximalPTH significantly decreased in intravenous group (1449±660versus 1122±691 pg/ml, P=0.0085) and at the limit ofstatistical significance in the intermittent oral group (1701±774versus 1445±634, P=0.12), but it did not change in thedaily oral group. Minimal PTH did not modify in the three groups.In all three groups, a shift to the right in the PTH-iCa relationshipswere observed, with significant changes in the set point ofcalcium. The slope of the post-treatment curves only becameless steep in the intermittent oral and intravenous groups. In conclusion, intermittent administration of calcitriol seemsto be more effective in reducing maximal PTH than daily oraladministration, but at the conditions under which this studywas carried out all the modes of calcitriol administration shiftedPTH-iCa relationships to the right. 相似文献
11.
The oophorectomized (OOX) rat has been proposed as a good model of postmenopausal osteroporosis in women. The aim of this
study was to compare the effect of OOX in 6-month-old rats to the effects of menopause in women with respect to bone mass,
the renal handling of calcium and phosphorus, and calcitropic hormones. To more closely replicate the human situation the
rats were pair fed a 0.1% calcium diet. Thirty four, 6-month-old rats were randomized to sham operation or OOX. Whole body
and regional bone density was performed at baseline and 6 weeks postoperation. Blood and 24-hour urine samples were obtained
at baseline, 1, 3, and 6 weeks and assayed for various biochemical variables, parathyroid hormone (PTH), and calcitriol. The
OOX rats lost significantly more bone than the sham-operated rats (change in global bone mineral density, sham −1.7 ± 2.0%,
OOX −3.9 ± 2.6%, P < 0.001). In the OOX animals, an increase in the 24-hour urine calcium was observed at 1 and 3 weeks, which had returned
to sham-operated levels by 6 weeks. In the whole group, the increase in urine calcium at 1 week was negatively correlated
with the change in bone mass at 6 weeks (r =−0.39, P= 0.029). OOX resulted in an increased filtered load of calcium and phosphorus. There was an increase in the maximal renal
tubular reabsorption of phosphorus (TmP-GFR) but no clear change in renal calcium handling. Neither calcitriol nor parathyroid
hormone showed a significant change as a result of OOX. As in postmenopausal women, following oophorectomy in the rat, there
was significant generalized bone loss and a negative calcium balance. This was associated with an initial rise in urine calcium
due to a rise in the filtered calcium load; plasma phosphorus and TmP-GFR also rose. The rat model may differ from postmenopausal
bone loss in that the initial rise in urine calcium was not present at later time points as occurs in natural menopause in
women. Calcitropic hormone levels did not change. This study has shown that the 6-month-old OOX rat fed a 0.1% calcium diet
has many similarities of calcium and phosphorus homeostasis to that seen at menopause in women.
Received: 14 August, 1995 / Accepted: 8 March 1996 相似文献
12.
Ardissino G Schmitt CP Testa S Claris-Appiani A Mehls O 《Pediatric nephrology (Berlin, Germany)》2000,14(7):664-668
Calcitriol oral pulse therapy has been suggested as the treatment of choice for secondary hyperparathyroidism, but its efficacy
and safety are still under discussion. The present randomized multicenter study compares the effect of an 8-week course of
daily versus intermittent (twice weekly) calcitriol therapy on parathyroid hormone (PTH) suppression in 59 children (mean
age 8.4±4.7 years) with chronic renal insufficiency (mean Ccr 22.4±11.6 ml/min per 1.73 m2) and secondary hyperparathyroidism. After a 3-week washout period, the patients were randomly assigned to treatment with
daily oral calcitriol (10 ng/kg per day) or intermittent oral calcitriol (35 ng/kg given twice a week). The calcitriol dose
was not changed throughout the study period of 8 weeks. At start of the study, the median intact PTH (iPTH) level was 485
pg/ml (range 83–2032) in the daily group (n=29) and 315 pg/ml (range 93–1638) in the intermittent group (n=30). After 8 weeks, the respective median iPTH concentrations were 232 pg/ml (range 63–1614) and 218 pg/ml (range 2–1785)
(ns). The mean iPTH decrease from baseline was 19.2±57.8% and 13.7±46.7% respectively (not significant). Calcitriol reduced
the iPTH concentration in 23/29 patients in the daily group and in 21/30 in the intermittent group. One episode of hypercalcemia
(>11.5 mg/dl) was observed in both groups and a single episode of hyperphosphatemia (>7.5 mg/dl) was observed in the daily
group. It is concluded that oral calcitriol pulse therapy does not control secondary hyperparathyroidism more effectively
than the daily administration of calcitriol in children with chronic renal failure prior to dialysis.
Received: 29 September 1999 / Revised: 2 February 2000 / Accepted: 9 February 2000 相似文献
13.
BACKGROUND: Calcitriol is widely used in conjunction with phosphorus-binders containing calcium to treat secondary hyperparathyroidism in dialysis patients. Its efficacy in patients with severe hyperparathyroidism is diminished, in part, due to glandular hyperplasia associated with decreased calcitriol and calcium receptors. SUBJECTS AND METHODS: We, therefore, developed a prospective, randomized trial comparing i.v. calcitriol plus calcium carbonate (CaCO3) compared to CaCO3 alone (control) in patients with mild to moderate hyperparathyroidism who were within the first year of initiating hemodialysis. Patients underwent calcium (Ca) suppression/stimulation testing at baseline and after six and twelve months of treatment to indirectly assess parathyroid gland hyperplasia. RESULTS: In the calcitriol group, the amino-terminal parathyroid hormone (N-PTH) decreased significantly from a baseline value of 70 +/- 12 pg/ml at month zero to 22 +/- 7 and 19 +/- 6 pg/ml at months 6 and 12, respectively (the conversion factor of amino-terminal PTH to intact PTH is 6, i.e., 10 pg/ml N-PTH equals 60 pg/ml intact PTH). In contrast, the N-PTH levels in the CaCO3 alone group did not change. The change in nadir N-PTH levels at month 12 compared to month zero decreased by 14 +/- 7% in the calcitriol group but increased by 96 +/- 59% in the control group (p < 0.05). In addition, the increment in N-PTH levels during hypocalcemic stimulation decreased by 68 +/- 6% at month 12 compared to month zero but increased by 61 +/- 42% in the control group. Although total calcium and phosphorus levels were not different between the two groups, ionized calcium values were higher in the calcitriol group. The incidence of hypercalcemia was the same in both groups and the episodes were asymptomatic. CONCLUSION: Pulse calcitriol therapy is effective in preventing progression of secondary hyperparathyroidism in hemodialysis patients with mild to moderate disease. Based on Ca suppression/stimulation tests, calcitriol was more successful in preventing gland growth than CaCO3 alone. Further studies are needed to determine if the strategy of early treatment of mild to moderate hyperparathyroidism by pulse calcitriol is safe and effective in hemodialysis in patients. 相似文献
14.
Either oral, intravenous or subcutaneous 1.25 (OH)2 cholecalciferol is used in the therapy of hyperparathyroidism, which is a serious complication in patients on haemodialysis.
We studied a total of 30 patients (10 women and 20 men) and divided them into two groups depending on the different types
of dialysis membranes used. In the poly sulfone group, mean age was 43.7±0.97 years and the average dialysis period lasted
29.9±1.23 months. For the 15 cases in which we used cuprophane membrane the mean age was 40.2±1.31 years and the average dialysis
period lasted 16.2±0.86 months. The calcium level of the dialysate in both groups was 1.5 mmol/l.
According to the study protocol, the determined oral calcitriol dose was 0.07 mg/kg and it was administered intermittently.
After one month on high dose calcitriol therapy, treatment was continued with a maintenance dose of 0.03 mg/kg for a further
six months. As a phosphate binding agent, daily 3 g calcium carbonate was administered.
Before starting this treatment protocol, patients went on a 1 mg/day calcitriol therapy, although the mean PTH level was 424.63
pg/ml and the mean serum alkaline phosphatase level was 290.2 U/l. During the pretreatment period, levels of PTH, alkaline
phosphatase, ionized calcium, and total calcium remained significantly within normal limits as a result of the new therapy
protocol applied.
PTH and phosphorus clearance rates were compared in the patient groups in which different dialysis membranes had been used.
PTH and phosphorus clearances were 15.2±3 ml/min and 239.1±19.2 ml/min, respectively, in the polysulfone membrane group, and
1.1±0.3 ml/min and 112.8±9.88 ml/min, respectively, in the cuprophane membrane group (p<0.05). 相似文献
15.
Absence of Calcitriol Causes Increased Lactational Bone Loss and Lower Milk Calcium but Does Not Impair Post‐lactation Bone Recovery in Cyp27b1 Null Mice
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Brittany R Gillies Brittany A Ryan Brett A Tonkin Ingrid J Poulton Yue Ma Beth J Kirby René St‐Arnaud Natalie A Sims Christopher S Kovacs 《Journal of bone and mineral research》2018,33(1):16-26
We hypothesized that adaptation to calcium supply demands of pregnancy and lactation do not require calcitriol. Adult Cyp27b1 null mice lack calcitriol and have hypocalcemia, hypophosphatemia, and rickets. We studied wild‐type (WT) and null sister pairs raised on a calcium‐, phosphorus‐, and lactose‐enriched “rescue” diet that prevents hypocalcemia and rickets. Bone mineral content (BMC) increased >30% in pregnant nulls, declined 30% during lactation, and increased 30% by 4 weeks post‐weaning. WT showed less marked changes. Micro‐CT revealed loss of trabecular bone and recovery in both genotypes. In lactating nulls, femoral cortical thickness declined >30%, whereas endocortical perimeter increased; both recovered to baseline after weaning; there were no such changes in WT. Histomorphometry revealed a profound increase in osteoid surface and thickness in lactating nulls, which recovered after weaning. By three‐point bend test, nulls had a >50% decline in ultimate load to failure that recovered after weaning. Although nulls showed bone loss during lactation, their milk calcium content was 30% lower compared with WT. Serum parathyroid hormone (PTH) was markedly elevated in nulls at baseline, reduced substantially in pregnancy, but increased again during lactation and remained high post‐weaning. In summary, pregnant Cyp27b1 nulls gained BMC with reduced secondary hyperparathyroidism, implying increased intestinal calcium delivery. Lactating nulls lost more bone mass and strength than WT, accompanied by increased osteoid, reduced milk calcium, and worsened secondary hyperparathyroidism. This implies suboptimal intestinal calcium absorption. Post‐weaning, bone mass and strength recovered to baseline, whereas BMC exceeded baseline by 40%. In conclusion, calcitriol‐independent mechanisms regulate intestinal calcium absorption and trabecular bone metabolism during pregnancy and post‐weaning but not during lactation; calcitriol may protect cortical bone during lactation. © 2017 American Society for Bone and Mineral Research. 相似文献
16.
Katherine Wesseling-Perry G. Chris Harkins He-Jing Wang Shobha Sahney Barbara Gales Robert M. Elashoff Harald Jüppner Isidro B. Salusky 《Pediatric nephrology (Berlin, Germany)》2009,24(7):1355-1361
Amino-terminally truncated parathyroid hormone (PTH) fragments are detected to differing degrees by first- and second-generation
immunometric PTH assays (PTH-IMAs), and acute changes in serum calcium affect the proportion of these fragments in circulation.
However, the effect of chronic calcium changes and different vitamin D doses on these PTH measurements remains to be defined.
In this study, 60 pediatric dialysis patients, aged 13.9 ± 0.7 years, with secondary hyperparathyroidism were randomized to
8 months of therapy with oral vitamin D combined with either calcium carbonate (CaCO3) or sevelamer. Serum phosphorus levels did not differ between groups. Serum calcium levels rose from 9.3 ± 0.1 to 9.7 ± 0.1 mg/dl
during CaCO3 therapy (p < 0.01 from baseline) but remained unchanged during sevelamer therapy. In the CaCO3 and sevelamer groups, baseline serum PTH levels (1st PTH-IMA; Nichols Institute Diagnostics, San Clemente, CA) were 964 ± 75 and
932 ± 89 pg/ml, and levels declined to 491 ± 55 and 543 ± 59 pg/ml, respectively (nonsignificant between groups). Patients
treated with sevelamer received higher doses of vitamin D than those treated with CaCO3. The PTH values obtained by first- and second-generation PTH-IMAs correlated closely throughout therapy and the response
of PTH was similar to both PTH-IMAs, despite differences in serum calcium levels. 相似文献
17.
Lindberg JS Moe SM Goodman WG Coburn JW Sprague SM Liu W Blaisdell PW Brenner RM Turner SA Martin KJ 《Kidney international》2003,63(1):248-254
BACKGROUND: A need exists for a therapy that lowers parathyroid hormone (PTH) without increasing calcium x phosphorus in patients with secondary hyperparathyroidism. The calcimimetic AMG 073 increases the sensitivity of the parathyroid calcium-sensing receptor to extracellular calcium, thereby reducing PTH secretion. Consequently, AMG 073 may provide a novel therapy for secondary hyperparathyroidism. METHODS: Seventy-eight hemodialysis patients with secondary hyperparathyroidism were enrolled into this 18-week, double-blind, randomized, placebo-controlled, dose titration study. Daily oral AMG 073 doses were administered to determine the effect on PTH, serum calcium, phosphorus, and calcium x phosphorus. RESULTS: The mean baseline PTH was similar in patients administered AMG 073 or placebo (632 +/- 280.1 pg/mL vs. 637 +/- 455.9 pg/mL, respectively). PTH decreased by 26.0% in the AMG 073-treated group, compared with an increase of 22.0% in the placebo group (P < 0.001). A greater proportion in the AMG 073 group (38%) had a decrease in PTH >or=30%, compared with the placebo group (8%) (P = 0.001). Decreases in PTH were independent of baseline vitamin D usage. Patients receiving AMG 073 had an 11.9% decrease in calcium x phosphorus compared with a 10.9% increase in the placebo group (P < 0.001). Use of vitamin D sterols, as well as both calcium and noncalcium-containing phosphate binders. were similar between treatment groups. Administration of AMG 073 was safe and well tolerated in this 18-week study. CONCLUSIONS: The calcimimetic AMG 073 decreases both PTH and calcium x phosphorus levels in hemodialysis patients with secondary hyperparathyroidism. 相似文献
18.
AIMS: BsmI polymorphism of the vitamin D receptor gene has been linked to hyperparathyroidism severity and calcitriol levels. The aim of this study was to analyze the response to a single bolus of calcitriol in hemodialysis patients with the BB and bb genotype. PATIENTS: Twenty homozygous BsmI hemodialysis patients (9 BB and 11 bb). METHODS: Hyperparathyroidism was assessed comparing basal PTH levels, and in 17 patients, also measuring the inhibition with hypercalcemia. Patients were given a bolus of calcitriol and PTH in absolute terms and in percentages relative to the baseline values at 24, 48 and 72 hours after the bolus were measured. All biochemical parameters were compared between genotypes with univariant ANOVA and additionally, PTH relative values were compared with general factorial analysis of variance, adjusting for calcium and phosphorus. Means were also compared within each genotype between consecutive determinations with non-parametric Wilcoxon analysis, using each patient as his/her own control. The response to calcitriol was also assessed by the area under the curve for each patient and was subsequently compared between genotypes. RESULTS: There were no differences on hyperparathyroidism severity between the groups. The BB genotype showed a better response than bb to calcitriol 72 hours after the bolus (percentage relative to basal PTH value: BB: 63%, bb: 88.6%, p = 0.03; BB vs bb with univariant ANOVA). When general factorial analysis of variance was applied, adjusting for serum calcium and phosphorus, genotype showed a significant influence on the response to calcitriol at 72 hours (p = 0.04). When each patient was used as his/her own control, the BB genotype showed a significant decrease in PTH levels at 48 and 72 hours (p = 0.00 baseline vs 48 h, and p = 0.01 baseline vs 72h) whereas the bb did not. CONCLUSIONS: BsmI polymorphism of the VDR gene induces differences on the response to a single bolus of calcitriol independently of calcium and phosphorus. 相似文献
19.
I. Berdud A. Martin-Malo Y. Almaden P. Aljama M. Rodriguez A. J. Felsenfeld 《Calcified tissue international》1998,62(5):457-461
To establish the PTH dosage that maintains normal mineral homeostasis in the PTX rat, a series of doses of rat 1-34 PTH were
infused via a subcutaneously implanted miniosmotic pump. The doses were 0, 0.011, 0.022, 0.044, and 0.11 μg/100 g/hour. After
48 hours, serum calcium ranged from 5.56 ± 0.02 to 16.29 ± 0.25 mg/dl, ANOVA P < 0.001, and serum phosphorus from 12.49 ± 0.03 to 5.33 ± 0.34 mg/dl, ANOVA P < 0.001. By post hoc test, the serum calcium level was different (P < 0.05) at every PTH dose; the serum phosphorus level was different (P < 0.05) at every PTH dose except between the two highest doses. The PTH dosage that produced a normal serum calcium (10.09
± 0.10 mg/dl) and phosphorus (6.90 ± 0.18 mg/dl) was 0.022 μg/100 g/hour. The relationship between increasing doses of PTH
and both serum calcium and phosphorus was curvilinear and the calcium-phosphorus product was remarkably constant from a serum
calcium of 7–13 mg/dl. The increase in serum calcium and the decrease in serum phosphorus were more rapid at lower than at
higher PTH doses so that for both, an asymptote was reached. At the highest serum calcium values, the calcium-phosphorus product
increased and in individual rats, an increase in serum phosphorus was associated with a decrease in serum calcium. In summary,
this study shows that (1) for rat 1-34 PTH, the normal replacement dose in the PTX rat with normal renal function on a normal
diet is 0.022 μg/100 g/hour; (2) the relationship between PTH and both serum calcium and phosphorus is curvilinear, and an
asymptote is reached for both; and (3) the calcium-phosphorus product is remarkably constant as the serum calcium increases
from 7 to 13 mg/dl and only increased during marked hypercalcemia when serum phosphorus did not decrease further or even tended
to increase.
Received: 30 May 1997 / Accepted: 15 October 1997 相似文献
20.
Ema J. Jamaluddin Abdul Halim Abdul Gafor Loo Chee Yean Rizna Cader Rozita Mohd Norella C. T. Kong Shamsul Azhar Shah 《Clinical and experimental nephrology》2014,18(3):507-514