Publications (9)21.86 Total impact
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Article: Cinacalcet treatment and serum FGF23 levels in haemodialysis patients with secondary hyperparathyroidism.
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ABSTRACT: Elevated fibroblast growth factor 23 (FGF23) is associated with adverse clinical outcomes and development of secondary hyperparathyroidism (SHPT) refractory to active vitamin D. Cinacalcet hydrochloride is effective in treating SHPT, but little is known as to whether treatment with cinacalcet alters these levels and whether pretreatment FGF23 levels predict response to this therapy. We measured serum full-length FGF23 levels in 55 haemodialysis patients, who participated and completed the 52-week, multicentre, open-label single-arm trial that examined the effectiveness of cinacalcet for treating SHPT. In the study, alteration of vitamin D dosage was not permitted except for the case in which serum calcium could not be managed by calcium carbonate adjustment alone. After 12 weeks of cinacalcet treatment, FGF23 levels decreased significantly concomitantly with a significant reduction in intact parathyroid hormone (PTH) levels. These responses were sustained >52 weeks. In multivariate regression analyses, changes from baseline in serum FGF23 were associated with changes in serum calcium and phosphorus but not with intact PTH at each time point of measurements (Week-12, Week-24 and Week-52). Baseline FGF23 was not associated with the likelihood of achieving an intact PTH <180 pg/mL at the study end. Cinacalcet lowers serum FGF23 in haemodialysis patients with SHPT independently of the effects of active vitamin D. Pretreatment FGF23 cannot predict treatment response to cinacalcet in this setting. The precise mechanism of FGF23 reduction by cinacalcet and its clinical impact on outcomes in patients remain to be investigated.Nephrology Dialysis Transplantation 07/2011; 27(2):784-90. · 3.40 Impact Factor -
Article: Clinical efficacy and cost-effectiveness of lanthanum carbonate as second-line therapy in hemodialysis patients in Japan.
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ABSTRACT: Lanthanum carbonate (LC) is a nonaluminum, noncalcium phosphate binder that is effective for hyperphosphatemia in dialysis patients. However, its efficacy and cost-effectiveness as second-line therapy have not been fully examined. We first conducted a multicenter, open-label, 16-week clinical trial to examine the effect of additive LC in 116 hemodialysis patients who had uncontrolled hyperphosphatemia with conventional phosphorus-lowering therapy alone. Based on these clinical data, a state transition model was developed to evaluate the benefits and costs associated with LC as second-line therapy. Reduced risks for cardiovascular morbidity and mortality among patients treated with LC arise through more of the population achieving the target phosphorus levels. Uncertainty was explored through sensitivity analysis. After 16 weeks of additive LC treatment, mean serum phosphorus levels decreased from 7.30 ± 0.90 to 5.71 ± 1.32 mg/dl, without significant changes in serum calcium or intact parathyroid hormone levels. A subsequent cost-effectiveness analysis showed that compared with conventional treatment, additive LC incurred an average additional lifetime cost of $22,054 per person and conferred an additional 0.632 quality-adjusted life years (QALYs). This resulted in an incremental cost-effectiveness ratio of $34,896 per QALY gained. Applying a cost-effectiveness threshold of $50,000 per QALY, a probabilistic sensitivity analysis showed that additive LC had a 97.4% probability of being cost-effective compared with conventional treatment. Our results indicate that the use of LC as second-line therapy would be cost-effective among hemodialysis patients with uncontrolled hyperphosphatemia in Japan.Clinical Journal of the American Society of Nephrology 06/2011; 6(6):1375-84. · 5.23 Impact Factor -
Article: Relationship between biochemical markers and radial cortical bone changes in hemodialysis patients.
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ABSTRACT: Bone loss in patients with osteoporosis may be predicted by the elevation of biochemical markers of bone turnover. Therefore, we studied the relationship between biochemical markers, including parathyroid hormone (PTH), and the 2-year change in radial cortical bone in patients under chronic hemodialysis. Tartrate-resistant acid phosphatase-5b (TRACP-5b), bone-specific alkaline phosphatase, whole PTH, and total intact PTH were measured in 53 patients under maintenance hemodialysis. Additionally, radial cortical bone mineral density (BMD) and relative cortical area (RCA) were measured by peripheral quantitative computed tomography 2 years apart. In all patients, BMD decreased by 2.5% and RCA decreased by 5.8% during 2 years. TRACP-5b levels significantly correlated with decreased RCA in all and female patients, but not with decreased BMD. Bone-specific alkaline phosphatase correlated with decreased BMD in all patients and with decreased RCA in all and female patients. Whole PTH did not correlate with decreased RCA or BMD. Total intact PTH significantly correlated with decreased BMD in all and male patients and with decreased RCA in all and female patients. In stepwise multiple regression analysis, TRACP-5b and total intact PTH were selected as explanatory variables for decreased RCA and decreased BMD, respectively. These results suggest that TRACP-5b and total intact PTH are powerful markers to predict radial cortical bone loss in hemodialysis patients.Nephron Clinical Practice 02/2011; 118(4):c375-9. · 2.04 Impact Factor -
Article: Effect of intravenous saccharated ferric oxide on serum FGF23 and mineral metabolism in hemodialysis patients.
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ABSTRACT: Fibroblast growth factor-23 (FGF23) plays a central role in the development of hypophosphatemia and inappropriately low 1,25-dihydroxyvitamin D induced by iron therapy for iron-deficiency anemia. The aim of this study was to examine the effect of intravenous saccharated ferric oxide on serum FGF23 levels and mineral metabolism in hemodialysis patients. This prospective study enrolled 27 hemodialysis patients who had iron-deficiency anemia defined by a hemoglobin concentration < 10.5 g/dl and serum ferritin < 100 ng/ml. Intravenous saccharated ferric oxide at a dose of 40 mg was administered three times weekly over 3 weeks. The dose of active vitamin D and phosphate binders was kept unchanged. Serum FGF23, intact parathyroid hormone (PTH) and other parameters were prospectively monitored for 5 weeks. Serum FGF23 levels were markedly elevated [3,453 (338-6,383) pg/ml] at baseline. After 3 weeks of intravenous saccharated ferric oxide treatment, serum FGF23 further increased to 4,701 (1,251-14,396) pg/ml, and returned to the baseline values after 2 weeks of observation. There was also a significant decrease in intact PTH but no changes in serum calcium and phosphorus. Intravenous saccharated ferric oxide induces further increase in elevated FGF23 levels in hemodialysis patients. This increase does not induce hypophosphatemia and inappropriately low 1,25-dihydroxyvitamin D in the absence of functioning kidney, but may result in transient PTH suppression - possibly by directly acting on the parathyroid.American Journal of Nephrology 01/2011; 33(5):421-6. · 2.54 Impact Factor -
Article: Cinacalcet effectively reduces parathyroid hormone secretion and gland volume regardless of pretreatment gland size in patients with secondary hyperparathyroidism.
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ABSTRACT: Cinacalcet is effective in reducing serum parathyroid hormone (PTH) in patients with secondary hyperparathyroidism. However, it has not been proven whether parathyroid gland size predicts response to therapy and whether cinacalcet is capable of inducing a reduction in parathyroid volume. This 52-week, multicenter, open-label study enrolled hemodialysis patients with moderate to severe secondary hyperparathyroidism (intact PTH >300 pg/ml). Doses of cinacalcet were adjusted between 25 and 100 mg to achieve intact PTH <180 pg/ml. Ultrasonography was performed to measure the parathyroid gland size at baseline, week 26, and week 52. Findings were also compared with those of historical controls. Of the 81 subjects enrolled, 56 had parathyroid glands smaller than 500 mm(3) (group S) and 25 had at least one enlarged gland larger than 500 mm(3) (group L). Treatment with cinacalcet effectively decreased intact PTH by 55% from baseline in group S and by 58% in group L. A slightly greater proportion of patients in group S versus group L achieved an intact PTH <180 pg/ml (46 versus 32%) and a >30% reduction from baseline (88 versus 78%), but this was not statistically significant. Cinacalcet therapy also resulted in a significant reduction in parathyroid gland volume regardless of pretreatment size, which was in sharp contrast to historical controls (n = 87) where parathyroid gland volume progressively increased with traditional therapy alone. Cinacalcet effectively decreases serum PTH levels and concomitantly reduces parathyroid gland volume, even in patients with marked parathyroid hyperplasia.Clinical Journal of the American Society of Nephrology 12/2010; 5(12):2305-14. · 5.23 Impact Factor -
Article: [Effects of reduced dialysate calcium on mineral metabolism in hemodialysis patients].
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ABSTRACT: To study the effects of decreased dialysis calcium on mineral metabolism. Dialysis calcium concentration was switched from 3.0 mEq/L to 2.5 mEq/L. Changes of serum Ca, P, and PTH were monitored for 6 months in 58 hemodialysis patients. Serum calcium decreased 2 weeks after the switch of dialysate, although it returned to the basal level after 6 months because of increased dosage of vitamin D. Phosphorus transiently increased after the switch. I-PTH increased in patients whose i-PTH before the switch was less than 100 pg/mL. PTH decreased in patients whose i-PTH exceeded 300 pg/mL. Decreased dialysis calcium produced lower serum calcium and better PTH control.Clinical calcium 10/2005; 15 Suppl 1:121-4; discussion 124. -
Article: Intravenous calcitriol therapy increases serum concentrations of fibroblast growth factor-23 in dialysis patients with secondary hyperparathyroidism.
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ABSTRACT: Fibroblast growth factor-23 (FGF-23) is a recently discovered phosphaturic factor. Although increased levels of serum FGF-23 have been reported in dialysis patients, the role of high FGF-23 levels remains unclear. Since FGF-23 is associated also with vitamin D metabolism, we examined the changes of serum FGF-23 levels in chronic dialysis patients treated with intravenous calcitriol therapy. Thirty patients with severe secondary hyperparathyroidism were treated with intravenous calcitriol (0.5-1.0 microg) two or three times per week for 6 months. The changes of serum levels of calcium, phosphate, intact PTH, and FGF-23 were evaluated. Baseline serum FGF-23 levels were markedly high. By intravenous calcitriol therapy, intact PTH levels decreased effectively in the first month (p < 0.001). In contrast, FGF-23 levels increased gradually during the study period (p = 0.027). The Delta serum FGF-23 level was significantly correlated with the total doses of calcitriol injected intravenously in 6 months in patients with refractory secondary hyperparathyroidism (R2 = 0.147; p = 0.036). Intravenous calcitriol decreased serum intact PTH level and increased serum FGF-23 levels significantly. Extremely high levels of serum FGF-23 in these patients may be attributed, at least in part, to the cumulative dose of vitamin D.Nephron Clinical Practice 01/2005; 101(2):c94-9. · 2.04 Impact Factor -
Article: Bio-intact parathyroid hormone and intact parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism receiving intravenous calcitriol therapy.
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ABSTRACT: Intact parathyroid hormone (iPTH) assay has been the most widely used for the diagnosis of secondary hyperparathyroidism and evaluation of vitamin D therapy. However, 1-84 PTH assay might be a better diagnostic tool since iPTH detects not only 1-84 PTH but also large C-terminal fragments, which would antagonize PTH action. Therefore, we conducted a multicenter study to evaluate the clinical usefulness of a newly developed immunochemiluminometric assay for 1-84 PTH, Bio-Intact PTH (BiPTH). Thirty-five uremic patients with secondary hyperparathyroidism participated in the study. Intravenous calcitriol therapy was continued for 12 months. iPTH and bone-specific alkaline phosphatase (BAP) were monitored at each dialysis center to control the dose of calcitriol. Serum and plasma samples were collected from each center and both iPTH and BiPTH were measured using Allegro-Lite assay reagents from Nichols Institute Diagnostics (San Clemente, CA, USA). Intravenous calcitriol suppressed iPTH after 1 month as well as BiPTH. Bone-specific alkaline phosphatase decreased after 3 months. A high degree of correlation between Nichols iPTH and BiPTH (y = 0.3913 x + 19.517, r = 0.9561) was demonstrated with a BiPTH/iPTH ratio of approximately 0.44. Significant correlation between BAP and iPTH, or between BAP and BiPTH was not observed. Our limited data failed to demonstrate the superiority of BiPTH to iPTH. Therefore, further investigations would be necessary to examine the relationship between BiPTH and bone histomorphometry.Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 01/2005; 8(6):474-9. · 1.39 Impact Factor -
Article: [Skeletal complications of renal insufficiency].
Nippon rinsho. Japanese journal of clinical medicine 03/2004; 62 Suppl 2:706-10.
