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1.
Aim: Calcitriol and alfacalcidol are used extensively for the treatment of secondary hyperparathyroidism. Unfortunately, there is limited published data comparing the efficacy and tolerability of both active vitamin D sterols. This study was undertaken to determine whether calcitriol provides a therapeutic advantage to alfacalcidol. Methods: This was a randomized, active controlled study. Patients with intact parathyroid hormone (iPTH) >32 pmol/L were randomized to receive orally calcitriol or alfacalcidol after each haemodialysis for up to 24 weeks. Reduction of PTH, changes of plasma albumin‐corrected calcium and phosphorus were analysed. The initial dose of alfacalcidol was twice that of calcitriol. Results: Sixteen patients were randomized into each group. At baseline, plasma albumin‐corrected calcium, phosphorus and PTH were no different between groups. At 24 weeks, PTH changes were ?50.8 ± 31.8% and ?49.4 ± 32.5% from the baseline in the calcitriol and alfacalcidol groups, respectively (P = 0.91). The patients who achieved target PTH of 16–32 pmol/L were 82% in the calcitriol and 67% in the alfacalcidol group (P = 0.44). Plasma albumin‐corrected calcium and phosphorus were not significantly different but showed trends toward gradually increasing from baseline in both groups (calcium, 6.0 ± 7.2% vs 10.9 ± 6.5% (P = 0.10); phosphorus, 13.0 ± 29.4% vs 16.7 ± 57.2% (P = 0.83) in calcitriol and alfacalcidol, respectively). The mean dose of calcitriol and alfacalcidol were 4.1 and 6.9 µg/week, respectively (P < 0.0001). Conclusion: Alfacalcidol can be used to control secondary hyperparathyroidism at doses of 1.5–2.0 times that of calcitriol. The two drugs are equally efficacious and lead to similar changes in calcium and phosphorus. 相似文献
2.
Relationship between parathyroid gland size and responsiveness to maxacalcitol therapy in patients with secondary hyperparathyroidism. 总被引:2,自引:0,他引:2
Senji Okuno Eiji Ishimura Kayoko Kitatani Hidenori Chou Kyoko Nagasue Kiyoshi Maekawa Tsuyoshi Izumotani Tomoyuki Yamakawa Yasuo Imanishi Tetsuo Shoji Masaaki Inaba Yoshiki Nishizawa 《Nephrology, dialysis, transplantation》2003,18(12):2613-2621
BACKGROUND: Although vitamin D has been reported to be useful in the treatment of patients with secondary hyperparathyroidism, it is not effective in some of them. The goal of this study was to see whether a relationship could be found between maxacalcitol responsiveness and parathyroid gland size. METHODS: Parathyroid gland size was measured by ultrasonography in 25 patients with secondary hyperparathyroidism [serum intact parathyroid hormone (PTH) >300 pg/ml, 58.1 +/- 2.8 years old, 15 males and 10 females], who were treated with maxacalcitol. Patients were divided into two groups according to the mean value of the maximum diameter of the glands: group S with a diameter <11.0 mm and group L with a diameter >or =11.0 mm. Between the two groups there were no significant differences in serum intact PTH, calcium or phosphate level or duration of haemodialysis. RESULTS: Mean (+/- SE) maximal diameter of detectable parathyroid glands was 11.0 +/- 0.7 mm before treatment. At 4-24 weeks after administration of maxacalcitol, intact PTH concentrations decreased significantly in group S (from 546 +/- 39 to 266 +/- 34 pg/ml at 24 weeks; P < 0.01), but did not significantly change in group L (from 481 +/- 39 to 403 +/- 49 pg/ml at 24 weeks). At 24 weeks after maxacalcitol administration, the number of detectable parathyroid glands was significantly decreased in group S (from 2.2 +/- 0.3 to 1.8 +/- 0.4; P < 0.05), but not in group L. Serum calcium increased significantly in group L (from 9.6 +/- 0.2 to 10.2 +/- 0.3 mg/dl; P < 0.05), but not in group S. There was a significant correlation between reduction in PTH and parathyroid gland size (r = -0.42, P < 0.05). CONCLUSIONS: These results indicate that the responsiveness to maxacalcitol therapy of secondary hyperparathyroidism is dependent on parathyroid gland size and that the simple measurement of maximum parathyroid gland diameter by ultrasonography may be useful for predicting responsiveness to maxacalcitol treatment. 相似文献
3.
André Falc?o Pedrosa Costa Luciene Machado dos Reis Melani Custódio Ribeiro Rosa Maria Affonso Moysés Vanda Jorgetti 《Nephrology, dialysis, transplantation》2003,18(4):743-749
BACKGROUND: Secondary hyperparathyroidism (2HPT) develops in chronic renal failure due to disturbances of calcium, phosphorus and vitamin D metabolism. It is characterized by high turnover bone disease and an altered calcium-parathyroid hormone (PTH) relationship. Calcitriol has been widely used for the treatment of 2HPT. However, it remains controversial whether calcitriol is capable of inducing changes of the calcium-PTH curve. The aim of the present study was to examine this issue and to determine the effect of calcitriol on bone remodelling in patients with severe 2HPT. METHODS: We evaluated 16 chronic haemodialysis patients with severe 2HPT (PTH 899+/-342 pg/ml). Each patient underwent a dynamic parathyroid function test (by infusion of calcium gluconate and sodium citrate) and a bone biopsy before and after a 6 month period of i.v. calcitriol therapy (CTx). RESULTS: After treatment, eight patients were identified as calcitriol responders and the other eight as non-responders, based on plasma PTH level (<300 pg/ml for responders and >300 pg/ml for non-responders). The first group had higher plasma 25OHD(3) levels (39+/-8 vs 24+/-7 ng/ml, P<0.005). As to the calcium-PTH curve, we found differences in slope (-12.7+/-5.2 vs -21.7+/-11.4, P=0.05), basal/maximum PTH ratio (48.8+/-14.9 vs 71.05+/-20.1%, P=0.01) and time to achieve hypocalcaemia (79.0+/-13.5 vs 94.3+/-13.7 min, P<0.001). Initial histomorphometric parameters did not allow identification of the different groups. After the 6-month CTx, alterations in the calcium-PTH curve were clearly seen in responders [a drop in maximum PTH (from 1651+/-616 to 938+/-744 pg/ml, P<0.05) and minimum PTH (from 163+/-75.4 to 102.2+/-56.7 pg/ml, P<0.005)], associated with an increase in minimum/basal PTH ratio (from 23.3+/-11.6 to 34.5+/-20.4%, P<0.05) and maximum calcium (from 0.99+/-0.07 to 1.1+/-0.09 mmol/l, P<0.05). Set point and slope were not altered after calcitriol treatment, in responders (set point=1.17+/-0.08 vs 1.15+/-0.1 mmol/l, ns; slope=-12.7+/-5.2 vs -12.9+/-9.3, ns) or non-responders (set point=1.21+/-0.05 vs 1.21+/-0.2 mmol/l, ns; slope=-21.7+/-11.4 vs -17.3+/-8.4, ns). Bone formation parameters were reduced in all patients [osteoid surface (OS/BS)=from 57.1+/-21.6 to 41.6+/-26%, P<0.05 for responders, and from 76.7+/-12 to 47.1+/-15%, P<0.001 in non-responders], but non-responders had increased bone resorption [eroded surface (ES/BS)=7.1+/-3.4 vs 16.6+/-4.9, P<0.05]. CONCLUSION: Calcitriol had non-uniform effects on parathyroid function and bone remodelling in uraemic patients. Non-responders exhibited a decoupled remodelling process that could further influence mineral balance or possibly also bone structure. To avoid such undesirable effects, early identification of non-responder patients is crucial when using calcitriol for the treatment of 2HPT. 相似文献
4.
5.
Long-term low-dose calcitriol treatment in predialysis chronic renal failure: can it prevent hyperparathyroid bone disease? 总被引:2,自引:0,他引:2
Nordal K. P.; Dahl E.; Halse J.; Attramadal A.; Flatmark A. 《Nephrology, dialysis, transplantation》1995,10(2):203-206
In an uncontrolled open study 13 patients with moderate to preterminalrenal failure were treated with low doses (average 0.36 µg/day)of calcitriol up to the time of renal transplantation, whichwas performed before dialysis had been initiated. A transiliacbone biopsy was obtained both at the start and at the end ofthe treatment period, the latter coinciding with renal transplantation.All patients who started calcitriol treatment at a creatinineclearance (Ccr) above 30 ml/min had normal bone histology atthe time of transplantation, but this was not observed whencalcitriol treatment was started at Ccr below 30 ml/min. The study suggests that full benefit of calcitriol at the bonelevel is obtained only if prophylactic administration is startedearly in the course of renal failure. 相似文献
6.
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
7.
M Kessler P Y Durand T C Huu M J Royer-Morot J Chanliau P Netter M Duc 《Nephrology, dialysis, transplantation》1999,14(11):2731-2733
BACKGROUND: It is now recognized that long-term exposure to even low levels of lead may increase bone lead content. Lead can then be released in toxicologically significant amounts during critical states of increased bone turnover. METHODS: Two patients with end-stage renal failure, one on haemodialysis and the other on continuous ambulatory peritoneal dialysis (CAPD), had been exposed to lead and developed secondary hyperparathyroidism. An edetate calcium disodium (EDTA) test was performed in combination with haemofiltration or CAPD before and after parathyroidectomy. RESULTS: Before parathyroidectomy, both patients had low delta aminolaevulinic acid dehydrase (ALA-D) and high concentrations of chelated lead. After parathyroidectomy, there was a dramatic decrease in chelated lead and the ALA-D returned to normal. CONCLUSION: Secondary hyperparathyroidism increases mobilization of bone lead in dialysis patients with an elevated lead burden. This may cause toxic effects. 相似文献
8.
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
9.
Hosaka K Kazama JJ Yamamoto S Ito Y Iino N Maruyama H Saito A Narita I Gejyo F 《Journal of bone and mineral metabolism》2008,26(2):185-190
Calcitriol therapy is a central strategy for the treatment of uremic secondary hyperparathyroidism. Although indiscriminate
use of calcitriol may lead to worse outcomes, it is difficult to make a decision to discontinue calcitriol therapy when its
parathyroid suppression effect remains unsatisfactory. In this study, intravenous calcitriol was administered to 120 chronic
hemodialysis patients. Therapy continued for 48 weeks or until plasma intact parathyroid hormone (iPTH) levels decreased to
below 300 pg/ml or until the development of any significant adverse effect. Of the 120 patients, the treatment goal was achieved
in 47 patients during the first 4 weeks, in 10 during the next 4 weeks, and in 22 patients thereafter. Logistic regression
analysis and stepwise regression analysis revealed that iPTH levels were the only significant predictor of the response to
calcitriol therapy at weeks 0 and 4. Besides iPTH, the inorganic phosphate (P) levels were another significant predictor of
the ultimate response to calcitriol therapy at week 8. The point of best discrimination for successful treatment was P = 6.0
mg/dl at week 8, or P level at week 8/pretreatment P level = 1.0. In conclusion, the P level at week 8 is a predictor of the
response to calcitriol therapy for uremic secondary hyperparathyroidism. Changes in treatment are recommended if patients
show unsatisfactory parathyroid suppression with a hyperphosphatemic tendency. 相似文献
10.
This study evaluates the effect of intravenous calcitriol on parathyroid function and ionized calcium-PTH sigmoidal curve obtained during low- and high-calcium haemodialysis in 10 patients with osteitis fibrosa whose secondary hyperparathyroidism was refractory to conventional therapy. After 4 months of intravenous calcitriol, serum ionized calcium increased from 1.28 +/- 0.08 to 1.37 +/- 0.11 mmol/l (P less than 0.001), serum phosphate from 1.54 +/- 0.18 to 1.79 +/- 0.4 mmol/l (P NS), serum calcitriol from 16.7 +/- 9.9 to 34.3 +/- 6.4 pg/ml (P less than 0.001), while alkaline phosphatase decreased from 366 +/- 340 to 226 +/- 180 IU/l (P less than 0.05), osteocalcin from 46.4 +/- 20 to 34.5 +/- 15.3 ng/ml (P less than 0.05), and basal intact PTH from 1069 +/- 700 to 305 +/- 270 (P less than 0.01). Basal PTH started to decrease after 1 month of treatment prior to the increase in the ionized calcium. Because of hypercalcaemia the dialysate calcium was decreased from 1.75 to 1.5 mmol/l in three of five patients on haemodialysis, and calcium-containing solutions were replaced by calcium-free fluids in four of five patients on haemodiafiltration. Calcitriol dose, at the first month of therapy was 5.6 +/- 0.8 micrograms/week, but it was successively decreased because of hypercalcaemia to a final dose of 3.6 +/- 1.3 micrograms/week. After intravenous calcitriol the ionized calcium-PTH sigmoidal curve shifted to the left and downward. Maximally stimulated PTH and maximally inhibited PTH obtained during low- and high-calcium dialysis significantly decreased, as well as the ratio of basal PTH/PTHmax and the set point of calcium.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
11.
Loke Meng Ong Punithavathi Narayanan Heong Keong Goh Anita Bhajan Manocha Ahmad Ghazali Mahanim Omar Sukeri Mohamad Bak‐Leong Goh Shahnaz Shah Mohd Ramli Seman Indralingam Vaithilingam Rozina Ghazalli Korina Rahmat Wan Shaariah Chen Hua Ching Oral Paricalcitol in ESRD Study Group 《Nephrology (Carlton, Vic.)》2013,18(3):194-200
12.
Junichiro J Kazama Kentaro Omori Noboru Higuchi Naoki Takahashi Yumi Ito Hiroki Maruyama Ichiei Narita Thomas L Cantor Ping Gao Fumitake Gejyo 《Nephrology, dialysis, transplantation》2004,19(4):892-897
BACKGROUND: Although the so-called intact parathyroid hormone (iPTH) assay detects not only true 1-84 PTH (1-84PTH) but also large C-terminal PTH fragments, it remains inconclusive whether the 1-84PTH assay is more useful in clinical practice. Previous studies have shown that the results of these two PTH assays in dialysis patients are closely correlated. METHODS: Chronic dialysis patients whose plasma iPTH levels were >400 pg/ml were selected for inclusion in the present study. Following a 4 week wash-out time during which all vitamin D administration was halted, maxacalcitol was intravenously injected at the end of dialysis sessions three times per week for 24 weeks, at an initial dosage of 10 micro g. RESULTS: Ninety-seven patients with secondary hyperparathyroidism were included in our analysis. Their serum calcium levels were elevated from the start levels while phosphate levels remained unchanged. The plasma 1-84PTH levels constantly declined throughout the 24 weeks. Although the patients' plasma 1-84PTH and iPTH levels were closely correlated with each other both at the beginning of the study and after 24 weeks of maxacalcitol therapy, the ratio of 1-84PTH/iPTH consistently decreased throughout the study period (P<0.01). The changes in the ratio were significantly correlated with changes in serum calcium levels. CONCLUSIONS: Twenty-four weeks of intravenous maxacalcitol injection therapy significantly reduced the 1-84PTH/iPTH ratio. Estimated 1-84PTH levels from iPTH levels using a conversion formula obtained before the treatment were 21.0+/-20.4% higher than measured 1-84PTH levels after the therapy. Thus, iPTH measurement has a potential risk to overestimate 1-84PTH levels when evaluating the efficacy of maxacalcitol therapy in dialysis patients with secondary hyperparathyroidism. 相似文献
13.
Mizumoto D.; Watanabe Y.; Fukuzawa Y.; Yuzawa Y.; Yamazaki C. 《Nephrology, dialysis, transplantation》1994,9(12):1751-1758
In order to evaluate the clinical outcome as well as the effectof vitamin D3 treatment on secondary hyperparathyroidism (SHPT)in the patients undergoing long-term dialysis therapy, we conducteda long-term follow-up survey on the demographic characteristicsof 425 patients who were observed for more than 3 years. Allpatients were treated with daily 1(OH)D3 treatment after theinitiation of dialysis. Among them the percentage of patientsneeding parathyroidectomy was 4.9% aggravation of SHPT, 11.8%an increase of the parathyroid hormone (PTH) level without radiographicalabnormalities, 17.4% stable, 56.2% and a decrease of the PTHlevel, 9.7% at the final observation. The average PTH levelsincreased year by year irrespective of the difference of originalrenal disease. Gender, age at the start of dialysis, originalrenal disease, duration of dialysis treatment, the decade ofstarting dialysis, the degree of phosphate control, and thePTH level at starting dialysis were analysed as potential riskfactors for SHPT, and assessed by multivariate analysis. Multivariateanalysis revealed that only the terms of duration of dialysisand the PTH level at starting dialysis were the significantrisks for developing overt SHPT. Logistic regression analysisrevealed that the relative risk was significantly higher inthe patients with more than 10 years history of dialysis andin those with the carboxyterminal PTH levels at the start ofdialysis being more than 5 ng/ml. These results suggest thatthe treatment with daily low-dose vitamin D3 administrationafter dialysis initiation is imperfect; therefore some prophylactictherapy from the predialysis stage is necessary to prevent overtSHPT, which will occur after long-term haemodialysis. 相似文献
14.
Malberti F.; Scanziani R.; Corradi B.; Dozio B.; Bonforte G.; Imbasciati E.; Surian M. 《Nephrology, dialysis, transplantation》1994,9(12):1813-1815
Abstract. We evaluated the effect of pulse oral calcitriol (4µg three times weekly for 6 months) on parathyroid functionin nine CAPD patients with hyperparathyroidism refractory toconventional lowdose oral calcitriol. Zero calcium peritonealsolutions were used to prevent the development of hypercalcaemia.The peritoneal loss of calcium increased from 168á40to 417á48 mg/day using zero calcium solutions. Pulseoral calcitriol resulted in a significant decrease in PTH (from617á272 to 382á299 pg/ml) by the 15th day of therapy,while serum iCa did not change from baseline. During the firstmonth of therapy the mean PTH levels remained significantlyreduced compared to baseline, thereafter PTH increased in fourof nine patients. Hyperphosphataemia was not satisfactorilycontrolled in four patients, despite large amounts of bindersused; seven of nine patients developed hypercalcaemia and requiredeither the substitution of calcium acetate for calcium carbonateor reduction of calcitriol dose. Three patients showed a progressiveincrease in PTH. In conclusion our data suggest that in mostCAPD patients with severe hyperparathyroidism oral calcitriolpulse therapy is not effective in maintaining a permanent suppressionin PTH levels. 相似文献
15.
Malberti F.; Corradi B.; Cosci P.; Colecchia M.; Leopardi O.; Grossi L.; Oldini C.; Imbasciati E. 《Nephrology, dialysis, transplantation》1996,11(1):81-87
BACKGROUND: The PTHcalcium sigmoidal curve is shifted to the right,the slope of the curve is steeper, and the set point of calciumis increased in dialysis patients with secondary hyperparathyroidism,compared to patients with low-turnover bone disease. These findingscould be related to increased parathyroid cell mass and increasedsensitivity of parathyroid cells to serum calcium variationsin these patients. Calcitriol therapy has been documented toreduce PTH levels by shifting the curve to the left and downward.The effect of a surgical reduction of parathyroid gland masson the PTH-calcium curve has not yet been investigated. In thisstudy we compared the effects of calcitriol and subtotal parathyroidectomy(PTH) on the dynamics of PTH secretion in response to acutechanges of serum calcium in two groups of dialysis patientswith severe hyperparathyroidism. METHODS: Fourteen dialysis patients treated for 6 months with high-dosei.v. calcitriol (12 µg thrice weekly), and 10 dialysispatients who underwent subtotal PTx were studied. The PTHcalciumrelationship obtained by inducing hypo- and hypercalcaemia bymeans of low and high calcium dialysis was evaluated beforeand 26 months after treatment. RESULTS: Both calcitriol and subtotal PTx significantly decreased PTH(respectively from 797±595 to 380±244 and from1036±250 to 70±34 pg/ml), as well as maximal PTHresponse to hypocalcaemia (PTHmax), and maximal PTH suppressionduring hypercalcaemia (PTHmin). When the PTHcalcium curveswere constructed using PTHmax as 100% to factor for differencesin absolute PTH levels and to provide an assessment of individualparathyroid cell function, a shift of the sigmoidal curve tothe left and downward, and a significant decrease in the setpoint of ionized calcium (from 1.31±0.05 to 1.26±0.05and from 1.36±0.09 to 1.22±0.07 mmol/1) was documentedwith both treatments. However, the slope of the PTHcalciumcurve increased after subtotal PTx indicating that the sensitivityof the parathyroid cell to serum calcium changes increased withPTx, while on the contrary it decreased with calcitriol. CONCLUSIONS: PTH secretion decreases proportionally more with calcitriolthan with surgery for a given decrease in the functional massof parathyroid cells. The change in the PTHICa sigmoidalcurve induced by subtotal PTx is due to the removal of a largemass of parathyroid tissue with advanced hyperplasia. 相似文献
16.
Secondary hyperparathyroidism is the most frequently encountered complication of chronic renal failure. In this paper, we
will summarize new insight into the pathogenesis of secondary hyperparathyroidism in chronic renal failure, with a special
emphasis on the regulation of PTH synthesis and parathyroid cell proliferation. 相似文献
17.
Effects of new vitamin D analogues on parathyroid function in chronically uraemic rats with secondary hyperparathyroidism 总被引:1,自引:1,他引:0
Hruby M.; Urena P.; Mannstadt M.; Schmitt F.; Lacour B.; Drueke T. B. 《Nephrology, dialysis, transplantation》1996,11(9):1781-1786
BACKGROUND.: Treatment with calcitriol or its analogue, alfacalcidol oftenleads to hypercalcaemia, hyperphosphataemia or both in patientswith chronic renal failure and advanced secondary hyperparathyroidism.We tested three new vitamin D analogues (CB 1093, EB 1213, GS1725) in an attempt to identify potentially non hypercalcaemiccompounds, capable of decreasing plasma parathyroid hormone(PTH) concentration. METHODS.: Male Wistar AF rats aged 1214 weeks were fed a synthetic,phosphate-rich diet and underwent either sham surgery (control)or a standard two-step 5/6th nephrectomy. Four weeks later,renal function was mildly decreased in the latter. Chronic renalfailure rats were then divided into six groups, with 810rats in each group. They received daily i.p. injections, fromdays 0 to 4, of either placebo, calcitriol, or one of the followingthree active vitamin D analogues: CB1093, 0.25 µg; EB1213,0.25 or 1.25 µg; and GS1725, 0.025 µg/kg body weightper day, respectively. Sham-operated rats received no drug.On day 5, arterial blood was sampled and rats were sacrificed. RESULTS.: At predefined dosage schedules, all three compounds significantlydecreased plasma immunoreactive PTH levels (except EB1213 atlow dose). The decrement was somewhat less marked than thatobtained with calcitriol, at the dose of 0.25 µg/kg b.w.per day. However, calcitriol induced a marked increase in plasmacalcium and phosphate concentrations at that dose, whereas vitaminD analogues led to a more modest increase in plasma calciumlevel, and none to a worsening of hyperphosphataemia. CB1093treatment was even associated with a significant decrease inplasma phosphate level. CONCLUSIONS.: All three calcitriol analogues tested are promising as non-hypercalcaemicagents in the treatment of uraemic secondary hyperparathyroidism.However, more prolonged administration to uraemic rats of calcitriolanalogues with slightly modified dosage schedules and of calcitriolwith lower, non-hypercalcaemic dose is required for an optimalcomparison before considering clinical trials. 相似文献
18.
Mochizuki T Naganuma S Tanaka Y Iwamoto Y Ishiguro C Kawashima Y Maekawa K Suda A Akiba T;TWMU Renal Osteodystrophy Study Group 《Clinical nephrology》2007,67(1):12-19
BACKGROUND: Maxacalcitol is a vitamin D analogue, which is administered intravenously for secondary hyperparathyroidism in dialysis patients as well as calcitriol. However, few dose-comparison clinical studies have been reported for these drugs. The present multicenter, randomized crossover study was conducted to determine the equivalence of maxacalcitol and calcitriol doses. METHODS: Subjects comprised 31 patients on chronic hemodialysis with secondary hyperparathyroidism who had not received maxacalcitol or calcitriol in the previous 3 months. Patients were randomly divided into two groups, and maxacalcitol or calcitriol was administered in a crossover design for 12 weeks each. Maxacalcitol and calcitriol doses were adjusted based on serum levels of calcium and intact parathyroid hormone. RESULTS: After the 12-week maxacalcitol/calcitriol administration, there were no significant differences in levels of calcium (maxacalcitol 2.40+/-0.22 mmol/1 (9.6+/-0.9 mg/dl), calcitriol 2.42 + 0.25 mmol/l (9.7+/-1.0 mg/dl), p = 0.71), phosphate (maxacalcitol 1.97 + 0.42 mmol/l (6.1+/-1.3 mg/dl), calcitriol 2.00+/-0.48 mmol/l (6.2+/-1.5 mg/dl), p = 0.64), intact parathyroid hormone (maxacalcitol 267+/-169 pg/ml, calcitriol 343+/-195 pg/ml, p = 0.11) in serum or other bone-metabolic parameters such as serum alkaline phosphatase. The doses ofmaxacalcitol and calcitriol were 49.3+/-23.7 microg/month and 9.0+/-3.8 microg/month, respectively, and maxacalcitol : calcitriol dose ratio was 5.5: 1. No severe adverse reactions were seen for either maxacalcitol or calcitriol during the study period. CONCLUSIONS: Comparable therapeutic efficacy can be obtained in the treatment of secondary hyperparathyroidism using either maxacalcitol or calcitriol at a dose ratio of 5.5 : 1. 相似文献
19.
Etoh S Murata T Hasegawa Y Miyahara Y Ishimura A Abe Y Noda R Ogahara S Kaneoka H Saito T 《Nephrology (Carlton, Vic.)》2004,9(3):161-166
METHODS AND RESULTS: In order to clarify the predialytic factors influencing the onset of secondary hyperparathyroidism (SHPT) in patients on chronic maintenance haemodialysis, the time-course changes of serum levels of intact-PTH (i-PTH) during haemodialysis for 5 years were investigated. The subjects were 69 non-diabetic patients who had a serum aluminium level of less than 1.85 nmol/L at the end of observation. Patients were divided into two groups based on i-PTH levels obtained at the start of dialysis; the high group (H group) consisted of patients whose i-PTH levels were more than 22.00 pmol/L, the low group (L group) had levels less than 22.00 pmol/L. In the H group, i-PTH was 41.46 +/- 2.87 pmol/L at the start of dialysis (vs L group, P < 0.0001) and 15.82 +/- 2.85 pmol/L after haemodialysis initiation. In the L group, i-PTH levels did not significantly change and was 11.69 +/- 2.50 pmol/L 12 months after the start of dialysis (at the 12th month). However, at the 60th month, the i-PTH level was 33.24 +/- 5.30 pmol/L in the H group, and 9.85 +/- 2.13 pmol/L in the L group (P < 0.005). CONCLUSION: It is suggested that control of i-PTH levels in the predialytic period may be important to suppress SHPT throughout haemodialysis. 相似文献
20.
Fumihiko Koiwa Takatoshi Kakuta Reika Tanaka Shigeru Yumita 《Nephrology, dialysis, transplantation》2007,22(2):522-528
BACKGROUND: Percutaneous ethanol injection therapy (PEIT) is used for advanced secondary hyperparathyroidism. We investigated the efficacy, remission period and risk of relapse to determine the effect of the number of hyperplastic glands and other factors on the therapeutic effect of PEIT. METHODS: We studied 321 patients divided into two groups: effective [serum corrected calcium (cCa) level < or =10.5 mg/dl and serum intact parathyroid hormone (iPTH) level < or =250 pg/ml], and ineffective (failed to achieve the target levels). Advanced hyperplasia was defined as an estimated volume > or =0.5 cm(3) on ultrasonography. RESULTS: PEIT was effective in 201 patients (62.6%), in whom serum iPTH levels dropped from 603+/-292 to 183+/-62 pg/ml (ng/l) and serum cCa levels from 10.7+/-0.8 to 10.1+/-0.5 mg/dl. Univariate analysis identified age, the number of hyperplastic glands and iPTH level as factors related to the efficacy of PEIT. The odds ratio for success vs failure by multivariate analysis was 0.55 times for the number of hyperplastic glands > or =0.5 cm(3) (> or =2 vs 0,1) and 0.29 times for iPTH (> or =500 vs <500 pg/ml). Using the Kaplan-Meier method, the number of hyperplastic glands > or =0.5 cm(3) (> or =2 vs 0,1) was a factor affecting the remission period, with a remission significantly longer seen in the group with one hyperplastic gland (P=0.0025). CONCLUSIONS: Superior results in efficacy rate, remission period and risk of relapse are obtained when PEIT is restricted to patients with one hyperplastic gland > or =0.5 cm(3). 相似文献