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William G Goodman - One of the best experts on this subject based on the ideXlab platform.
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long term treatment of Secondary Hyperparathyroidism with the calcimimetic cinacalcet hcl
Nephrology Dialysis Transplantation, 2005Co-Authors: Sharon M Moe, Matthew Guo, John Cunningham, Jurgen Bommer, Stephen Adler, Steven J Rosansky, Pablo Urenatorres, Moetaz Albizem, Valter J Zani, William G GoodmanAbstract:Background. Patients with Secondary Hyperparathyroidism often require therapy that provides longterm control of parathyroid hormone concentrations without increasing calcium and phosphorus concentrations. Cinacalcet modulates the calcium-sensing receptor on the parathyroid gland to reduce secretion of parathyroid hormone and lower serum calcium, phosphorus and calcium–phosphorus product in haemodialysis patients. Methods. Dialysis patients with Secondary Hyperparathyroidism [parathyroid hormone (PTH) level � 300 pg/ml] who were enrolled in one of four phase 2 placebo-controlled studies were eligible to enrol in an open-label extension study in which all patients received cinacalcet. For this extension study, cinacalcet was initiated at 30 mg in all patients and the dose was escalated to a maximum of 180 mg once daily if PTH concentrations were >250 pg/ml. Use of concomitant vitamin D sterols and phosphate binders was not restricted. Results. The analysis of all patients (n ¼ 59) completing 100 weeks of cinacalcet treatment showed long-term control of PTH and calcium–phosphorus product. Approximately 55% achieved a PTH concentration � 300 pg/ml at the week-100 study visit, and � 60% had at least a 30% reduction in PTH from baseline. Serum calcium, phosphorus and the calcium–phosphorus product did not increase during the study. Concomitant vitamin D sterol and phosphate binder therapy remained stable. Cinacalcet was safe and generally well tolerated at doses up to 180 mg/day. Conclusions. In this long-term study, cinacalcet effectively sustained reductions in PTH for up to 3 years without increasing concentrations of serum calcium, phosphorus or calcium–phosphorus product.
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the calcimimetic amg 073 reduces parathyroid hormone and calcium x phosphorus in Secondary Hyperparathyroidism
Kidney International, 2003Co-Authors: Jill S Lindberg, Stewart A. Turner, William G Goodman, Wei Liu, Jack W Coburn, Sharon M Moe, Stuart M Sprague, Peter W Blaisdell, Robert M Brenner, Kevin J MartinAbstract:The calcimimetic AMG 073 reduces parathyroid hormone and calcium x phosphorus in Secondary Hyperparathyroidism. 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 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 Conclusions The calcimimetic AMG 073 decreases both PTH and calcium x phosphorus levels in hemodialysis patients with Secondary Hyperparathyroidism.
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a calcimimetic agent lowers plasma parathyroid hormone levels in patients with Secondary Hyperparathyroidism
Kidney International, 2000Co-Authors: William G Goodman, Stewart A. Turner, Joao M Frazao, David A Goodkin, Wei Liu, Jack W CoburnAbstract:A calcimimetic agent lowers plasma parathyroid hormone levels in patients with Secondary Hyperparathyroidism. Background The calcimimetic agent R-568 lowers plasma parathyroid hormone (PTH) levels in hemodialysis patients with mild Secondary Hyperparathyroidism, but its efficacy in those with more severe Secondary Hyperparathyroidism has not been studied. Methods Twenty-one patients undergoing hemodialysis three times per week with plasma PTH levels between 300 and 1200 pg/mL were randomly assigned to 15 days of treatment with either 100 mg of R-568 ( N = 16) or placebo ( N = 5). Plasma PTH and blood ionized calcium levels were measured at intervals of up to 24 hours after oral doses on days 1, 2, 3, 5, 8, 11, 12, and 15. Results Pretreatment PTH levels were 599 ± 105 (mean ± SE) and 600 ± 90 pg/mL in subjects given R-568 or placebo, respectively, and values on the first day of treatment did not change in those given placebo. In contrast, PTH levels fell by 66 ± 5%, 78 ± 3%, and 70 ± 3% at one, two, and four hours, respectively, after initial doses of R-568, remaining below pretreatment values for 24 hours. Blood ionized calcium levels also decreased after the first dose of R-568 but did not change in patients given placebo. Despite lower ionized calcium concentrations on both the second and third days of treatment, predose PTH levels were 422 ± 70 and 443 ± 105 pg/mL, respectively, in patients given R-568, and values fell each day by more than 50% two hours after drug administration. Predose PTH levels declined progressively over the first nine days of treatment with R-568 and remained below pretreatment levels for the duration of study. Serum total and blood ionized calcium concentrations decreased from pretreatment levels in patients given R-568, whereas values were unchanged in those given placebo. Blood ionized calcium levels fell below 1.0 mmol/L in 7 of 16 patients receiving R-568; five patients withdrew from study after developing symptoms of hypocalcemia, whereas three completed treatment after the dose of R-568 was reduced. Conclusions The calcimimetic R-568 rapidly and markedly lowers plasma PTH levels in patients with Secondary Hyperparathyroidism caused by end-stage renal disease.
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in vivo assessments of calcium regulated parathyroid hormone release in Secondary Hyperparathyroidism
Kidney International, 1996Co-Authors: William G Goodman, Thomas R Belin, Isidro B. SaluskyAbstract:In vivo dynamic tests of parathyroid gland function have provided useful information about the secretory behavior of parathyroids in various clinical disorders, but the limitations of this approach must be recognized when applied to studies of parathyroid gland physiology. Set point abnormalities have been documented in vivo both in primary Hyperparathyroidism and in familial hypocalciuric hypercalcemia. Such findings are consistent with in vitro results obtained in studies of dispersed parathyroid cells from patients with primary Hyperparathyroidism and with recently described alteration in calcium receptor expression in patients with FHH. The assessment of parathyroid gland function in patients with end-stage renal disease presents distinct methodological problems, however, because of marked variation in the degree of parathyroid gland enlargement. Neither the four parameter model originally used to describe set point abnormalities both in vitro and in vivo or alternative approaches to the assessment of PTH secretion in vivo adequately address this important issue. Results from recent in vivo studies of patients with chronic renal failure do not support the view that the set point for calcium-regulated PTH release is abnormal in Secondary Hyperparathyroidism or that treatment with calcitriol lowers the set point for calcium-regulated PTH release in patients with uremic Secondary Hyperparathyroidism. The concept of set point disturbances has strongly influenced discussions about the pathogenesis of Secondary Hyperparathyroidism, and it has served as a focal point for examining the therapeutic response to calcitriol in patients with this disorder. This matter requires careful reconsideration, however, in light of recent clinical findings and the development of techniques to directly assess the molecular mechanisms responsible for regulating calcium-mediated PTH release in renal failure and other disorders of mineral metabolism. Although knowledge in this area remains limited, the extent of parathyroid hyperplasia and the role of factors that influence the development of parathyroid gland enlargement may ultimately prove to be particularly important modifiers of parathyroid gland function in chronic renal failure.
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calcium regulated parathyroid hormone release in patients with mild or advanced Secondary Hyperparathyroidism
Kidney International, 1995Co-Authors: William G Goodman, Barbara Gales, Thomas R Belin, Harald Juppner, Gino V Segre, Isidro B. SaluskyAbstract:Calcium-regulated parathyroid hormone release in patients with mild or advanced Secondary Hyperparathyroidism. Differences in the regulation of parathyroid hormone (PTH) release by calcium are thought to account for excess PTH secretion in patients with Secondary Hyperparathyroidism (2°HPTH). To determine whether calcium-regulated PTH release varies with the severity of 2°HPTH in patients with end-stage renal disease, dynamic tests of parathyroid gland function were done using the four-parameter model in 26 patients with 2°HPTH documented by bone biopsy. Estimates of the set point did not differ among patients categorized as mild (basal serum PTH 600 pg/ml) 2°HPTH; values were 1.23 ± 0.06 mmol/liter, 1.24 ± 0.06 mmol/liter and 1.23 ± 0.05 mmol/liter, respectively, and none of these set point estimates differed from results obtained in normal volunteers, 1.21 ± 0.02 mmol/liter (NS). The slope of the sigmoidal ionized calcium-PTH curve also did not differ among groups. Set point values did not correspond to basal serum PTH levels, to the maximum serum PTH level observed during hypocalcemia or to the minimum serum PTH level seen during hypercalcemia in patients with 2°HPTH. In contrast, basal serum PTH values were positively correlated with both the maximum serum PTH level observed during hypocalcemia (r = 0.76, P in vivo dynamic tests of parathyroid gland function. The results suggest that variations in parathyroid gland size are the major contributor to excessive PTH secretion in patients with chronic renal failure.
Isidro B. Salusky - One of the best experts on this subject based on the ideXlab platform.
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intermittent calcitriol therapy in Secondary Hyperparathyroidism a comparison between oral and intraperitoneal administration
Kidney International, 1998Co-Authors: Jorge A Ramirez, Barbara Gales, Beatriz D Kuizon, Isidro B. Salusky, Thomas R BelinAbstract:Intermittent calcitriol therapy in Secondary Hyperparathyroidism: A comparison between oral and intraperitoneal administration. Background Intermittent oral or intravenous doses of calcitriol given two or three times per week are commonly used to treat Secondary Hyperparathyroidism (2° HPT). This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal (i.p.) versus oral doses of calcitriol in children with 2° HPT undergoing peritoneal dialysis (CCPD). Methods Forty-six patients aged 12.5 ± 4.8years on CCPD for 22 ± 25months were randomly assigned to treatment with oral (p.o.) or i.p. calcitriol for 12months; 17 subjects given p.o. calcitriol and 16 subjects given i.p. calcitriol completed the study. Bone biopsies were performed at the beginning and at the end of the study, while determinations of serum and total ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and calcitriol levels were done monthly. Results Serum total and ionized calcium levels were higher in subjects treated with i.p. calcitriol, P P P P Conclusion Differences in the bioavailability of calcitriol and/or in phosphorus metabolism may account for the divergent biochemical response to p.o. and i.p. calcitriol.
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in vivo assessments of calcium regulated parathyroid hormone release in Secondary Hyperparathyroidism
Kidney International, 1996Co-Authors: William G Goodman, Thomas R Belin, Isidro B. SaluskyAbstract:In vivo dynamic tests of parathyroid gland function have provided useful information about the secretory behavior of parathyroids in various clinical disorders, but the limitations of this approach must be recognized when applied to studies of parathyroid gland physiology. Set point abnormalities have been documented in vivo both in primary Hyperparathyroidism and in familial hypocalciuric hypercalcemia. Such findings are consistent with in vitro results obtained in studies of dispersed parathyroid cells from patients with primary Hyperparathyroidism and with recently described alteration in calcium receptor expression in patients with FHH. The assessment of parathyroid gland function in patients with end-stage renal disease presents distinct methodological problems, however, because of marked variation in the degree of parathyroid gland enlargement. Neither the four parameter model originally used to describe set point abnormalities both in vitro and in vivo or alternative approaches to the assessment of PTH secretion in vivo adequately address this important issue. Results from recent in vivo studies of patients with chronic renal failure do not support the view that the set point for calcium-regulated PTH release is abnormal in Secondary Hyperparathyroidism or that treatment with calcitriol lowers the set point for calcium-regulated PTH release in patients with uremic Secondary Hyperparathyroidism. The concept of set point disturbances has strongly influenced discussions about the pathogenesis of Secondary Hyperparathyroidism, and it has served as a focal point for examining the therapeutic response to calcitriol in patients with this disorder. This matter requires careful reconsideration, however, in light of recent clinical findings and the development of techniques to directly assess the molecular mechanisms responsible for regulating calcium-mediated PTH release in renal failure and other disorders of mineral metabolism. Although knowledge in this area remains limited, the extent of parathyroid hyperplasia and the role of factors that influence the development of parathyroid gland enlargement may ultimately prove to be particularly important modifiers of parathyroid gland function in chronic renal failure.
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calcium regulated parathyroid hormone release in patients with mild or advanced Secondary Hyperparathyroidism
Kidney International, 1995Co-Authors: William G Goodman, Barbara Gales, Thomas R Belin, Harald Juppner, Gino V Segre, Isidro B. SaluskyAbstract:Calcium-regulated parathyroid hormone release in patients with mild or advanced Secondary Hyperparathyroidism. Differences in the regulation of parathyroid hormone (PTH) release by calcium are thought to account for excess PTH secretion in patients with Secondary Hyperparathyroidism (2°HPTH). To determine whether calcium-regulated PTH release varies with the severity of 2°HPTH in patients with end-stage renal disease, dynamic tests of parathyroid gland function were done using the four-parameter model in 26 patients with 2°HPTH documented by bone biopsy. Estimates of the set point did not differ among patients categorized as mild (basal serum PTH 600 pg/ml) 2°HPTH; values were 1.23 ± 0.06 mmol/liter, 1.24 ± 0.06 mmol/liter and 1.23 ± 0.05 mmol/liter, respectively, and none of these set point estimates differed from results obtained in normal volunteers, 1.21 ± 0.02 mmol/liter (NS). The slope of the sigmoidal ionized calcium-PTH curve also did not differ among groups. Set point values did not correspond to basal serum PTH levels, to the maximum serum PTH level observed during hypocalcemia or to the minimum serum PTH level seen during hypercalcemia in patients with 2°HPTH. In contrast, basal serum PTH values were positively correlated with both the maximum serum PTH level observed during hypocalcemia (r = 0.76, P in vivo dynamic tests of parathyroid gland function. The results suggest that variations in parathyroid gland size are the major contributor to excessive PTH secretion in patients with chronic renal failure.
Barbara Gales - One of the best experts on this subject based on the ideXlab platform.
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intermittent calcitriol therapy in Secondary Hyperparathyroidism a comparison between oral and intraperitoneal administration
Kidney International, 1998Co-Authors: Jorge A Ramirez, Barbara Gales, Beatriz D Kuizon, Isidro B. Salusky, Thomas R BelinAbstract:Intermittent calcitriol therapy in Secondary Hyperparathyroidism: A comparison between oral and intraperitoneal administration. Background Intermittent oral or intravenous doses of calcitriol given two or three times per week are commonly used to treat Secondary Hyperparathyroidism (2° HPT). This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal (i.p.) versus oral doses of calcitriol in children with 2° HPT undergoing peritoneal dialysis (CCPD). Methods Forty-six patients aged 12.5 ± 4.8years on CCPD for 22 ± 25months were randomly assigned to treatment with oral (p.o.) or i.p. calcitriol for 12months; 17 subjects given p.o. calcitriol and 16 subjects given i.p. calcitriol completed the study. Bone biopsies were performed at the beginning and at the end of the study, while determinations of serum and total ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and calcitriol levels were done monthly. Results Serum total and ionized calcium levels were higher in subjects treated with i.p. calcitriol, P P P P Conclusion Differences in the bioavailability of calcitriol and/or in phosphorus metabolism may account for the divergent biochemical response to p.o. and i.p. calcitriol.
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calcium regulated parathyroid hormone release in patients with mild or advanced Secondary Hyperparathyroidism
Kidney International, 1995Co-Authors: William G Goodman, Barbara Gales, Thomas R Belin, Harald Juppner, Gino V Segre, Isidro B. SaluskyAbstract:Calcium-regulated parathyroid hormone release in patients with mild or advanced Secondary Hyperparathyroidism. Differences in the regulation of parathyroid hormone (PTH) release by calcium are thought to account for excess PTH secretion in patients with Secondary Hyperparathyroidism (2°HPTH). To determine whether calcium-regulated PTH release varies with the severity of 2°HPTH in patients with end-stage renal disease, dynamic tests of parathyroid gland function were done using the four-parameter model in 26 patients with 2°HPTH documented by bone biopsy. Estimates of the set point did not differ among patients categorized as mild (basal serum PTH 600 pg/ml) 2°HPTH; values were 1.23 ± 0.06 mmol/liter, 1.24 ± 0.06 mmol/liter and 1.23 ± 0.05 mmol/liter, respectively, and none of these set point estimates differed from results obtained in normal volunteers, 1.21 ± 0.02 mmol/liter (NS). The slope of the sigmoidal ionized calcium-PTH curve also did not differ among groups. Set point values did not correspond to basal serum PTH levels, to the maximum serum PTH level observed during hypocalcemia or to the minimum serum PTH level seen during hypercalcemia in patients with 2°HPTH. In contrast, basal serum PTH values were positively correlated with both the maximum serum PTH level observed during hypocalcemia (r = 0.76, P in vivo dynamic tests of parathyroid gland function. The results suggest that variations in parathyroid gland size are the major contributor to excessive PTH secretion in patients with chronic renal failure.
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development of adynamic bone in patients with Secondary Hyperparathyroidism after intermittent calcitriol therapy
Kidney International, 1994Co-Authors: Jorge A Ramirez, Barbara Gales, Thomas R Belin, William G Goodman, Yun ChonAbstract:Development of adynamic bone in patients with Secondary Hyperparathyroidism after intermittent calcitriol therapy. Intermittent calcitriol therapy is commonly used to treat Secondary Hyperparathyroidism in patients undergoing regular dialysis, but there is little available information about the histologic response of bone to this form of therapy. Accordingly, 14 children and adolescents with biopsy-proven Secondary Hyperparathyroidism were treated with intermittent oral or intraperitoneal doses of calcitriol for 12 months. Biochemical indices of mineral metabolism including serum intact PTH levels were measured monthly throughout the study, and bone biopsies were repeated at the end of treatment. Before treatment, 11 patients had osteitis fibrosa and three had mild lesions of Secondary Hyperparathyroidism. Histologic improvement was seen in 12 of 14 patients, and osteitis fibrosa resolved in 10 of 11 cases. Bone formation decreased in all patients during intermittent calcitriol therapy, falling from 861 ± 380 to 150 ± 170 µm 2 /mm 2 /day, P
Thomas R Belin - One of the best experts on this subject based on the ideXlab platform.
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intermittent calcitriol therapy in Secondary Hyperparathyroidism a comparison between oral and intraperitoneal administration
Kidney International, 1998Co-Authors: Jorge A Ramirez, Barbara Gales, Beatriz D Kuizon, Isidro B. Salusky, Thomas R BelinAbstract:Intermittent calcitriol therapy in Secondary Hyperparathyroidism: A comparison between oral and intraperitoneal administration. Background Intermittent oral or intravenous doses of calcitriol given two or three times per week are commonly used to treat Secondary Hyperparathyroidism (2° HPT). This study was undertaken to compare the biochemical and skeletal responses to thrice weekly intraperitoneal (i.p.) versus oral doses of calcitriol in children with 2° HPT undergoing peritoneal dialysis (CCPD). Methods Forty-six patients aged 12.5 ± 4.8years on CCPD for 22 ± 25months were randomly assigned to treatment with oral (p.o.) or i.p. calcitriol for 12months; 17 subjects given p.o. calcitriol and 16 subjects given i.p. calcitriol completed the study. Bone biopsies were performed at the beginning and at the end of the study, while determinations of serum and total ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and calcitriol levels were done monthly. Results Serum total and ionized calcium levels were higher in subjects treated with i.p. calcitriol, P P P P Conclusion Differences in the bioavailability of calcitriol and/or in phosphorus metabolism may account for the divergent biochemical response to p.o. and i.p. calcitriol.
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in vivo assessments of calcium regulated parathyroid hormone release in Secondary Hyperparathyroidism
Kidney International, 1996Co-Authors: William G Goodman, Thomas R Belin, Isidro B. SaluskyAbstract:In vivo dynamic tests of parathyroid gland function have provided useful information about the secretory behavior of parathyroids in various clinical disorders, but the limitations of this approach must be recognized when applied to studies of parathyroid gland physiology. Set point abnormalities have been documented in vivo both in primary Hyperparathyroidism and in familial hypocalciuric hypercalcemia. Such findings are consistent with in vitro results obtained in studies of dispersed parathyroid cells from patients with primary Hyperparathyroidism and with recently described alteration in calcium receptor expression in patients with FHH. The assessment of parathyroid gland function in patients with end-stage renal disease presents distinct methodological problems, however, because of marked variation in the degree of parathyroid gland enlargement. Neither the four parameter model originally used to describe set point abnormalities both in vitro and in vivo or alternative approaches to the assessment of PTH secretion in vivo adequately address this important issue. Results from recent in vivo studies of patients with chronic renal failure do not support the view that the set point for calcium-regulated PTH release is abnormal in Secondary Hyperparathyroidism or that treatment with calcitriol lowers the set point for calcium-regulated PTH release in patients with uremic Secondary Hyperparathyroidism. The concept of set point disturbances has strongly influenced discussions about the pathogenesis of Secondary Hyperparathyroidism, and it has served as a focal point for examining the therapeutic response to calcitriol in patients with this disorder. This matter requires careful reconsideration, however, in light of recent clinical findings and the development of techniques to directly assess the molecular mechanisms responsible for regulating calcium-mediated PTH release in renal failure and other disorders of mineral metabolism. Although knowledge in this area remains limited, the extent of parathyroid hyperplasia and the role of factors that influence the development of parathyroid gland enlargement may ultimately prove to be particularly important modifiers of parathyroid gland function in chronic renal failure.
-
calcium regulated parathyroid hormone release in patients with mild or advanced Secondary Hyperparathyroidism
Kidney International, 1995Co-Authors: William G Goodman, Barbara Gales, Thomas R Belin, Harald Juppner, Gino V Segre, Isidro B. SaluskyAbstract:Calcium-regulated parathyroid hormone release in patients with mild or advanced Secondary Hyperparathyroidism. Differences in the regulation of parathyroid hormone (PTH) release by calcium are thought to account for excess PTH secretion in patients with Secondary Hyperparathyroidism (2°HPTH). To determine whether calcium-regulated PTH release varies with the severity of 2°HPTH in patients with end-stage renal disease, dynamic tests of parathyroid gland function were done using the four-parameter model in 26 patients with 2°HPTH documented by bone biopsy. Estimates of the set point did not differ among patients categorized as mild (basal serum PTH 600 pg/ml) 2°HPTH; values were 1.23 ± 0.06 mmol/liter, 1.24 ± 0.06 mmol/liter and 1.23 ± 0.05 mmol/liter, respectively, and none of these set point estimates differed from results obtained in normal volunteers, 1.21 ± 0.02 mmol/liter (NS). The slope of the sigmoidal ionized calcium-PTH curve also did not differ among groups. Set point values did not correspond to basal serum PTH levels, to the maximum serum PTH level observed during hypocalcemia or to the minimum serum PTH level seen during hypercalcemia in patients with 2°HPTH. In contrast, basal serum PTH values were positively correlated with both the maximum serum PTH level observed during hypocalcemia (r = 0.76, P in vivo dynamic tests of parathyroid gland function. The results suggest that variations in parathyroid gland size are the major contributor to excessive PTH secretion in patients with chronic renal failure.
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development of adynamic bone in patients with Secondary Hyperparathyroidism after intermittent calcitriol therapy
Kidney International, 1994Co-Authors: Jorge A Ramirez, Barbara Gales, Thomas R Belin, William G Goodman, Yun ChonAbstract:Development of adynamic bone in patients with Secondary Hyperparathyroidism after intermittent calcitriol therapy. Intermittent calcitriol therapy is commonly used to treat Secondary Hyperparathyroidism in patients undergoing regular dialysis, but there is little available information about the histologic response of bone to this form of therapy. Accordingly, 14 children and adolescents with biopsy-proven Secondary Hyperparathyroidism were treated with intermittent oral or intraperitoneal doses of calcitriol for 12 months. Biochemical indices of mineral metabolism including serum intact PTH levels were measured monthly throughout the study, and bone biopsies were repeated at the end of treatment. Before treatment, 11 patients had osteitis fibrosa and three had mild lesions of Secondary Hyperparathyroidism. Histologic improvement was seen in 12 of 14 patients, and osteitis fibrosa resolved in 10 of 11 cases. Bone formation decreased in all patients during intermittent calcitriol therapy, falling from 861 ± 380 to 150 ± 170 µm 2 /mm 2 /day, P
Stewart A. Turner - One of the best experts on this subject based on the ideXlab platform.
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cinacalcet for Secondary Hyperparathyroidism in patients receiving hemodialysis
The New England Journal of Medicine, 2004Co-Authors: Geoffrey A Block, Stewart A. Turner, Kevin J Martin, Angel L M De Francisco, Morrell M Avram, Michael Suranyi, Gavril Hercz, John Cunningham, Ali K Abualfa, Piergiorgio MessaAbstract:BACKGROUND: Treatment of Secondary Hyperparathyroidism with vitamin D and calcium in patients receiving dialysis is often complicated by hypercalcemia and hyperphosphatemia, which may contribute to cardiovascular disease and adverse clinical outcomes. Calcimimetics target the calcium-sensing receptor and lower parathyroid hormone levels without increasing calcium and phosphorus levels. We report the results of two identical randomized, double-blind, placebo-controlled trials evaluating the safety and effectiveness of the calcimimetic agent cinacalcet hydrochloride. METHODS: Patients who were receiving hemodialysis and who had inadequately controlled Secondary Hyperparathyroidism despite standard treatment were randomly assigned to receive cinacalcet (371 patients) or placebo (370 patients) for 26 weeks. Once-daily doses were increased from 30 mg to 180 mg to achieve intact parathyroid hormone levels of 250 pg per milliliter or less. The primary end point was the percentage of patients with values in this range during a 14-week efficacy-assessment phase. RESULTS: Forty-three percent of the cinacalcet group reached the primary end point, as compared with 5 percent of the placebo group (P<0.001). Overall, mean parathyroid hormone values decreased 43 percent in those receiving cinacalcet but increased 9 percent in the placebo group (P<0.001). The serum calcium-phosphorus product declined by 15 percent in the cinacalcet group and remained unchanged in the placebo group (P<0.001). Cinacalcet effectively reduced parathyroid hormone levels independently of disease severity or changes in vitamin D sterol dose. CONCLUSIONS: Cinacalcet lowers parathyroid hormone levels and improves calcium-phosphorus homeostasis in patients receiving hemodialysis who have uncontrolled Secondary Hyperparathyroidism.
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the calcimimetic amg 073 as a potential treatment for Secondary Hyperparathyroidism of end stage renal disease
Journal of The American Society of Nephrology, 2003Co-Authors: Darryl L Quarles, Stewart A. Turner, Laura C Mccary, Stephen Adler, Steven J Rosansky, Donald J Sherrard, David A BushinskyAbstract:Current treatment of Secondary Hyperparathyroidism in chronic kidney failure with calcium and active vitamin D is potentially limited by hypercalcemia and hyperphosphatemia. AMG 073 represents a new class of compounds for the treat- ment of Hyperparathyroidism known as calcimimetics, which reduce parathyroid hormone (PTH) synthesis and secretion by increasing the sensitivity of the parathyroid calcium-sensing receptor (CaR) to extracellular calcium. The current study evaluates the efficacy and safety of AMG 073 when added to conventional treatment of Secondary Hyperparathyroidism in end-stage renal disease (ESRD). Seventy-one hemodialysis patients with uncontrolled Secondary Hyperparathyroidism, de- spite standard therapy with calcium, phosphate binders, and active vitamin D sterols, were treated in this 18-wk, dose- titration study with single daily oral doses of AMG 073/ placebo up to 100 mg. Changes in plasma PTH, serum calcium, serum phosphorus, and calcium phosphorus levels were compared between AMG 073 and placebo groups. Mean PTH decreased by 33% in the AMG 073 patients compared with an increase of 3% in placebo patients (P 0.001). A significantly greater proportion of AMG 073 patients (44%) had a mean PTH 250 pg/ml compared with placebo patients (20%; P 0.029). Also, a significantly greater proportion of AMG 073 patients (53%) had a decrease in PTH 30% compared with placebo patients (23%; P 0.009). Calcium phosphorus levels decreased by 7.9% in AMG 073 patients compared with an increase of 11.3% in placebo patients (P 0.013). Adverse event rates were low and mostly mild to moderate in severity; however, the incidence of vomiting was higher in AMG 073 patients. In this study, the calcimimetic AMG 073 at doses up to 100 mg for 18 wk provided a safe and effective means to attain significant reductions in PTH and calcium phosphorus levels in ESRD patients. AMG 073 represents a novel and promising therapy to improve the management of Secondary Hyperparathyroidism.
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the calcimimetic amg 073 as a potential treatment for Secondary Hyperparathyroidism of end stage renal disease
Journal of The American Society of Nephrology, 2003Co-Authors: Darryl L Quarles, Stewart A. Turner, Wei Liu, Laura C Mccary, Stephen Adler, Steven J Rosansky, Donald J Sherrard, David A BushinskyAbstract:Current treatment of Secondary Hyperparathyroidism in chronic kidney failure with calcium and active vitamin D is potentially limited by hypercalcemia and hyperphosphatemia. AMG 073 represents a new class of compounds for the treatment of Hyperparathyroidism known as calcimimetics, which reduce parathyroid hormone (PTH) synthesis and secretion by increasing the sensitivity of the parathyroid calcium-sensing receptor (CaR) to extracellular calcium. The current study evaluates the efficacy and safety of AMG 073 when added to conventional treatment of Secondary Hyperparathyroidism in end-stage renal disease (ESRD). Seventy-one hemodialysis patients with uncontrolled Secondary Hyperparathyroidism, despite standard therapy with calcium, phosphate binders, and active vitamin D sterols, were treated in this 18-wk, dose-titration study with single daily oral doses of AMG 073/placebo up to 100 mg. Changes in plasma PTH, serum calcium, serum phosphorus, and calcium x phosphorus levels were compared between AMG 073 and placebo groups. Mean PTH decreased by 33% in the AMG 073 patients compared with an increase of 3% in placebo patients (P = 0.001). A significantly greater proportion of AMG 073 patients (44%) had a mean PTH or =30% compared with placebo patients (23%; P = 0.009). Calcium x phosphorus levels decreased by 7.9% in AMG 073 patients compared with an increase of 11.3% in placebo patients (P = 0.013). Adverse event rates were low and mostly mild to moderate in severity; however, the incidence of vomiting was higher in AMG 073 patients. In this study, the calcimimetic AMG 073 at doses up to 100 mg for 18 wk provided a safe and effective means to attain significant reductions in PTH and calcium x phosphorus levels in ESRD patients. AMG 073 represents a novel and promising therapy to improve the management of Secondary Hyperparathyroidism.
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the calcimimetic amg 073 reduces parathyroid hormone and calcium x phosphorus in Secondary Hyperparathyroidism
Kidney International, 2003Co-Authors: Jill S Lindberg, Stewart A. Turner, William G Goodman, Wei Liu, Jack W Coburn, Sharon M Moe, Stuart M Sprague, Peter W Blaisdell, Robert M Brenner, Kevin J MartinAbstract:The calcimimetic AMG 073 reduces parathyroid hormone and calcium x phosphorus in Secondary Hyperparathyroidism. 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 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 Conclusions The calcimimetic AMG 073 decreases both PTH and calcium x phosphorus levels in hemodialysis patients with Secondary Hyperparathyroidism.
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a calcimimetic agent lowers plasma parathyroid hormone levels in patients with Secondary Hyperparathyroidism
Kidney International, 2000Co-Authors: William G Goodman, Stewart A. Turner, Joao M Frazao, David A Goodkin, Wei Liu, Jack W CoburnAbstract:A calcimimetic agent lowers plasma parathyroid hormone levels in patients with Secondary Hyperparathyroidism. Background The calcimimetic agent R-568 lowers plasma parathyroid hormone (PTH) levels in hemodialysis patients with mild Secondary Hyperparathyroidism, but its efficacy in those with more severe Secondary Hyperparathyroidism has not been studied. Methods Twenty-one patients undergoing hemodialysis three times per week with plasma PTH levels between 300 and 1200 pg/mL were randomly assigned to 15 days of treatment with either 100 mg of R-568 ( N = 16) or placebo ( N = 5). Plasma PTH and blood ionized calcium levels were measured at intervals of up to 24 hours after oral doses on days 1, 2, 3, 5, 8, 11, 12, and 15. Results Pretreatment PTH levels were 599 ± 105 (mean ± SE) and 600 ± 90 pg/mL in subjects given R-568 or placebo, respectively, and values on the first day of treatment did not change in those given placebo. In contrast, PTH levels fell by 66 ± 5%, 78 ± 3%, and 70 ± 3% at one, two, and four hours, respectively, after initial doses of R-568, remaining below pretreatment values for 24 hours. Blood ionized calcium levels also decreased after the first dose of R-568 but did not change in patients given placebo. Despite lower ionized calcium concentrations on both the second and third days of treatment, predose PTH levels were 422 ± 70 and 443 ± 105 pg/mL, respectively, in patients given R-568, and values fell each day by more than 50% two hours after drug administration. Predose PTH levels declined progressively over the first nine days of treatment with R-568 and remained below pretreatment levels for the duration of study. Serum total and blood ionized calcium concentrations decreased from pretreatment levels in patients given R-568, whereas values were unchanged in those given placebo. Blood ionized calcium levels fell below 1.0 mmol/L in 7 of 16 patients receiving R-568; five patients withdrew from study after developing symptoms of hypocalcemia, whereas three completed treatment after the dose of R-568 was reduced. Conclusions The calcimimetic R-568 rapidly and markedly lowers plasma PTH levels in patients with Secondary Hyperparathyroidism caused by end-stage renal disease.