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Chen H. Hsu - One of the best experts on this subject based on the ideXlab platform.
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An open‐label, crossover study of a new Phosphate‐Binding Agent in haemodialysis patients: ferric citrate
Nephrology Dialysis Transplantation, 2002Co-Authors: Wu Chang Yang, Chwei Shiun Yang, Chun Chen Hou, Eric W. Young, Chen H. HsuAbstract:AbstractBackground. Hyperphosphataemia contributes to sec-ondary hyperparathyroidism and renal osteodystrophyin patients with end-stage renal disease (ESRD).Calcium salts are widely employed to bind dietaryPhosphate (P) but they may promote positive netcalcium balance and metastatic calcification. Werecently reported that ferric compounds bind intestinalPhosphate in studies of normal and azotemic rats.Methods. To extend this observation, we performed anopen-label, random order, crossover comparison studyof ferric citrate and calcium carbonate in haemodia-lysis patients from two teaching hospitals. The studysample consisted of 23 women and 22 men with anaverage age of 52.5"11.8 (SD) years and an averageweight of 54.5"10.7 kg. All forms of iron therapy werediscontinued. Two weeks before the study, patientswere instructed to discontinue all P-Binding Agents.The patients were randomly assigned to receive eithercalcium carbonate (3 guday) or ferric citrate (3 guday)for 4 weeks followed by a 2 week washout period, andthen crossed over to the other P-Binding Agent for4 weeks.Results. From a baseline concentration of 5.6"1.5 mgudl, the serum P increased during the washoutperiod to 7.2"1.9 mgudl prior to calcium carbonatetreatment, and to 6.7"1.9 mgudl prior to ferric citratetreatment. The serum P concentration fell signific-antly during treatment with both calcium carbonate(7.2"1.9 to 5.2"1.5 mgudl, P-0.0001) and ferriccitrate (6.7"1.9 to 5.7"1.6 mgudl, P-0.0001). Theresults were not influenced by order of treatment.Under the conditions of the study protocol, ferriccitrate was less effective than calcium carbonateat lowering the serum Phosphate concentration.The serum Ca concentration increased during treat-ment with calcium carbonate but not ferric citrate.Ferric citrate treatment did not affect the serumconcentration of aluminium. Ferric citrate treatmentwas associated with mild and generally tolerablegastrointestinal symptoms.Conclusion. Ferric citrate shows promise as a meansof lowering the serum Phosphate concentration inhaemodialysis patients. Further studies are needed tofind the optimal dose.Keywords: ferric citrate; haemodialysis; open-labelcrossover study; Phosphate-Binding Agent
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an open label crossover study of a new Phosphate Binding Agent in haemodialysis patients ferric citrate
Nephrology Dialysis Transplantation, 2002Co-Authors: Wu Chang Yang, Chwei Shiun Yang, Chun Chen Hou, Eric W. Young, Chen H. HsuAbstract:AbstractBackground. Hyperphosphataemia contributes to sec-ondary hyperparathyroidism and renal osteodystrophyin patients with end-stage renal disease (ESRD).Calcium salts are widely employed to bind dietaryPhosphate (P) but they may promote positive netcalcium balance and metastatic calcification. Werecently reported that ferric compounds bind intestinalPhosphate in studies of normal and azotemic rats.Methods. To extend this observation, we performed anopen-label, random order, crossover comparison studyof ferric citrate and calcium carbonate in haemodia-lysis patients from two teaching hospitals. The studysample consisted of 23 women and 22 men with anaverage age of 52.5"11.8 (SD) years and an averageweight of 54.5"10.7 kg. All forms of iron therapy werediscontinued. Two weeks before the study, patientswere instructed to discontinue all P-Binding Agents.The patients were randomly assigned to receive eithercalcium carbonate (3 guday) or ferric citrate (3 guday)for 4 weeks followed by a 2 week washout period, andthen crossed over to the other P-Binding Agent for4 weeks.Results. From a baseline concentration of 5.6"1.5 mgudl, the serum P increased during the washoutperiod to 7.2"1.9 mgudl prior to calcium carbonatetreatment, and to 6.7"1.9 mgudl prior to ferric citratetreatment. The serum P concentration fell signific-antly during treatment with both calcium carbonate(7.2"1.9 to 5.2"1.5 mgudl, P-0.0001) and ferriccitrate (6.7"1.9 to 5.7"1.6 mgudl, P-0.0001). Theresults were not influenced by order of treatment.Under the conditions of the study protocol, ferriccitrate was less effective than calcium carbonateat lowering the serum Phosphate concentration.The serum Ca concentration increased during treat-ment with calcium carbonate but not ferric citrate.Ferric citrate treatment did not affect the serumconcentration of aluminium. Ferric citrate treatmentwas associated with mild and generally tolerablegastrointestinal symptoms.Conclusion. Ferric citrate shows promise as a meansof lowering the serum Phosphate concentration inhaemodialysis patients. Further studies are needed tofind the optimal dose.Keywords: ferric citrate; haemodialysis; open-labelcrossover study; Phosphate-Binding Agent
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are we mismanaging calcium and Phosphate metabolism in renal failure
American Journal of Kidney Diseases, 1997Co-Authors: Chen H. HsuAbstract:Secondary hyperparathyroidism and renal osteodystrophy are the consequences of abnormal calcium, Phosphate, and calcitriol metabolism ensuing from renal failure. Evidence suggests that calcium balance tends to become negative as we grow older than 35 years of age; however, the current dialysis modalities provide patients regardless of age with excessive calcium during dialysis. Administration of calcitriol in the management of hyperparathyroidism further increases the calcium and Phosphate absorption. Furthermore, the current thrice-weekly renal replacement therapies fail to remove the daily absorbed Phosphate, and we have to use calcium carbonate as a primary Phosphate-Binding Agent to reduce intestinal Phosphate absorption. The large calcium mass transfer and Phosphate retention could lead to soft tissue calcification, especially in older end-stage renal disease (ESRD) patients. Consequently, only by maintaining a negative calcium balance during renal replacement therapy can we safely use calcitriol and calcium carbonate for the management of secondary hyperparathyroidism. Recent studies have indicated that Phosphate restriction alone independent of plasma calcitriol or calcium can lower plasma parathyroid hormone (PTH) in renal failure and prevent hyperplasia of parathyroid glands. Therefore, Phosphate control perhaps is the most important means to prevent secondary hyperparathyroidism. Previous studies have shown that ferric compounds are potent Phosphate-Binding Agents; hence, these compounds warrant further trial in the management of Phosphate metabolism in renal failure.
Cheryl P Sanchez - One of the best experts on this subject based on the ideXlab platform.
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Prevention and Treatment of Renal Osteodystrophy in Children With Chronic Renal Insufficiency and End-Stage Renal Disease
Seminars in Nephrology, 2001Co-Authors: Cheryl P SanchezAbstract:Histologic features associated with secondary hyperparathyroidism remain the predominant skeletal lesion in adults and children with chronic renal failure. When instituted early, vitamin D therapy has been shown to ameliorate the development and progression of the biochemical, radiographic, and histologic evidence of secondary hyperparathyroidism in patients with chronic renal insufficiency. Aggressive parathyroid hormone suppression, however, has led to the increased prevalence of adynamic bone. Adynamic bone has been attributed partly to aggressive calcitriol therapy, administration of high amounts of exogenous calcium either as a Phosphate Binding Agent or during dialysis therapy, presence of diabetes, older age, or previous parathyroidectomy. Several vitamin D analogues are currently being evaluated in patients with chronic renal failure to prevent complications associated with calcltriol therapy. In addition, calcium-free Phosphate Binding Agents and the use of calcimimetic drugs may playa significant role in the effective management of secondary hyperparathyroidism in children with chronic renal failure.
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calcium regulated parathyroid hormone secretion in adynamic renal osteodystrophy
Kidney International, 1995Co-Authors: Jorge A Ramirez, William G. Goodman, Barbara Gales, Cheryl P Sanchez, Thomas R BelinAbstract:Calcium-regulated parathyroid hormone secretion in adynamic renal osteodystrophy. Hypercalcemia and low serum parathyroid hormone (PTH) levels are features of the adynamic lesion (AD) of renal osteodystrophy, but there is little information about parathyroid gland function in this disorder. Therefore, the four parameter model was used to evaluate calcium-regulated PTH release in patients with either adynamic bone or secondary hyperparathyroidism (OF) as documented by bone biopsy and in normal volunteers (NL). Patients had undergone CCPD for 20 ± 4.2 months, and all received calcium carbonate as the sole Phosphate-Binding Agent. During two hours infusions of sodium citrate, the rate of decline in serum ionized calcium levels did not differ among groups; serum PTH levels rose from 136 ± 38 to 342 ± 140 pg/ml in AD and from 691 ± 99 to 869 ±121 pg/ml in OF. Maximum PTH levels were 322 ± 42% of baseline values in AD but only 146 ± 9.7% of baseline in OF (P
Wu Chang Yang - One of the best experts on this subject based on the ideXlab platform.
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An open‐label, crossover study of a new Phosphate‐Binding Agent in haemodialysis patients: ferric citrate
Nephrology Dialysis Transplantation, 2002Co-Authors: Wu Chang Yang, Chwei Shiun Yang, Chun Chen Hou, Eric W. Young, Chen H. HsuAbstract:AbstractBackground. Hyperphosphataemia contributes to sec-ondary hyperparathyroidism and renal osteodystrophyin patients with end-stage renal disease (ESRD).Calcium salts are widely employed to bind dietaryPhosphate (P) but they may promote positive netcalcium balance and metastatic calcification. Werecently reported that ferric compounds bind intestinalPhosphate in studies of normal and azotemic rats.Methods. To extend this observation, we performed anopen-label, random order, crossover comparison studyof ferric citrate and calcium carbonate in haemodia-lysis patients from two teaching hospitals. The studysample consisted of 23 women and 22 men with anaverage age of 52.5"11.8 (SD) years and an averageweight of 54.5"10.7 kg. All forms of iron therapy werediscontinued. Two weeks before the study, patientswere instructed to discontinue all P-Binding Agents.The patients were randomly assigned to receive eithercalcium carbonate (3 guday) or ferric citrate (3 guday)for 4 weeks followed by a 2 week washout period, andthen crossed over to the other P-Binding Agent for4 weeks.Results. From a baseline concentration of 5.6"1.5 mgudl, the serum P increased during the washoutperiod to 7.2"1.9 mgudl prior to calcium carbonatetreatment, and to 6.7"1.9 mgudl prior to ferric citratetreatment. The serum P concentration fell signific-antly during treatment with both calcium carbonate(7.2"1.9 to 5.2"1.5 mgudl, P-0.0001) and ferriccitrate (6.7"1.9 to 5.7"1.6 mgudl, P-0.0001). Theresults were not influenced by order of treatment.Under the conditions of the study protocol, ferriccitrate was less effective than calcium carbonateat lowering the serum Phosphate concentration.The serum Ca concentration increased during treat-ment with calcium carbonate but not ferric citrate.Ferric citrate treatment did not affect the serumconcentration of aluminium. Ferric citrate treatmentwas associated with mild and generally tolerablegastrointestinal symptoms.Conclusion. Ferric citrate shows promise as a meansof lowering the serum Phosphate concentration inhaemodialysis patients. Further studies are needed tofind the optimal dose.Keywords: ferric citrate; haemodialysis; open-labelcrossover study; Phosphate-Binding Agent
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an open label crossover study of a new Phosphate Binding Agent in haemodialysis patients ferric citrate
Nephrology Dialysis Transplantation, 2002Co-Authors: Wu Chang Yang, Chwei Shiun Yang, Chun Chen Hou, Eric W. Young, Chen H. HsuAbstract:AbstractBackground. Hyperphosphataemia contributes to sec-ondary hyperparathyroidism and renal osteodystrophyin patients with end-stage renal disease (ESRD).Calcium salts are widely employed to bind dietaryPhosphate (P) but they may promote positive netcalcium balance and metastatic calcification. Werecently reported that ferric compounds bind intestinalPhosphate in studies of normal and azotemic rats.Methods. To extend this observation, we performed anopen-label, random order, crossover comparison studyof ferric citrate and calcium carbonate in haemodia-lysis patients from two teaching hospitals. The studysample consisted of 23 women and 22 men with anaverage age of 52.5"11.8 (SD) years and an averageweight of 54.5"10.7 kg. All forms of iron therapy werediscontinued. Two weeks before the study, patientswere instructed to discontinue all P-Binding Agents.The patients were randomly assigned to receive eithercalcium carbonate (3 guday) or ferric citrate (3 guday)for 4 weeks followed by a 2 week washout period, andthen crossed over to the other P-Binding Agent for4 weeks.Results. From a baseline concentration of 5.6"1.5 mgudl, the serum P increased during the washoutperiod to 7.2"1.9 mgudl prior to calcium carbonatetreatment, and to 6.7"1.9 mgudl prior to ferric citratetreatment. The serum P concentration fell signific-antly during treatment with both calcium carbonate(7.2"1.9 to 5.2"1.5 mgudl, P-0.0001) and ferriccitrate (6.7"1.9 to 5.7"1.6 mgudl, P-0.0001). Theresults were not influenced by order of treatment.Under the conditions of the study protocol, ferriccitrate was less effective than calcium carbonateat lowering the serum Phosphate concentration.The serum Ca concentration increased during treat-ment with calcium carbonate but not ferric citrate.Ferric citrate treatment did not affect the serumconcentration of aluminium. Ferric citrate treatmentwas associated with mild and generally tolerablegastrointestinal symptoms.Conclusion. Ferric citrate shows promise as a meansof lowering the serum Phosphate concentration inhaemodialysis patients. Further studies are needed tofind the optimal dose.Keywords: ferric citrate; haemodialysis; open-labelcrossover study; Phosphate-Binding Agent
William G. Goodman - One of the best experts on this subject based on the ideXlab platform.
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Medical management of secondary hyperparathyroidism in chronic renal failure.
Nephrology dialysis transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2003Co-Authors: William G. GoodmanAbstract:Abnormalities in calcium and phosphorus metabolism are common, and metabolic bone disease develops often in patients with chronic renal failure (CRF). Effective clinical management includes measures to control phosphorus retention and prevent hyperphosphataemia, to maintain serum calcium concentrations within the normal range and to prevent excess parathyroid hormone (PTH) secretion by the judicious use of vitamin D sterols. Certain of these interventions appear to increase the risk of soft tissue and vascular calcification in patients with end-stage renal disease (ESRD), changes that may contribute to the development of cardiovascular disease. Current therapeutic approaches are thus being re-evaluated in an effort to limit these risks. Despite the importance of controlling phosphorus retention and preventing hyperphosphataemia in patients with CRF, current management strategies often are inadequate, particularly in those ingesting diets containing adequate amounts of protein. Results from clinical trials using daily haemodialysis strongly suggest that thrice-weekly haemodialysis regimens are only marginally adequate for achieving weekly phosphorus balance in many patients with ESRD. The safety of large oral doses of calcium as a Phosphate-Binding Agent in patients with ESRD has also been questioned because excess amounts of calcium that are absorbed from the gastrointestinal tract may lead to ongoing calcium retention in those with little or no residual renal function. Arterial calcification and cardiac valve calcification are two serious complications that adversely affect cardiovascular haemodynamics. The use of large, often supraphysiological, doses of calcitriol or other vitamin D sterols to treat secondary hyperparathyroidism may aggravate hypercalcaemia and hyperphosphataemia, further increasing the risk of soft tissue and vascular calcification. Phosphate-Binding Agents that do not contain calcium, new vitamin D analogues and calcimimetic compounds offer new therapeutic alternatives for managing renal osteodystrophy. The integration of these novel Agents into existing treatment regimens may provide safer and more effective methods for controlling secondary hyperparathyroidism and renal bone disease, while limiting the risks of soft tissue and vascular calcification in patients with CRF.
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calcium regulated parathyroid hormone secretion in adynamic renal osteodystrophy
Kidney International, 1995Co-Authors: Jorge A Ramirez, William G. Goodman, Barbara Gales, Cheryl P Sanchez, Thomas R BelinAbstract:Calcium-regulated parathyroid hormone secretion in adynamic renal osteodystrophy. Hypercalcemia and low serum parathyroid hormone (PTH) levels are features of the adynamic lesion (AD) of renal osteodystrophy, but there is little information about parathyroid gland function in this disorder. Therefore, the four parameter model was used to evaluate calcium-regulated PTH release in patients with either adynamic bone or secondary hyperparathyroidism (OF) as documented by bone biopsy and in normal volunteers (NL). Patients had undergone CCPD for 20 ± 4.2 months, and all received calcium carbonate as the sole Phosphate-Binding Agent. During two hours infusions of sodium citrate, the rate of decline in serum ionized calcium levels did not differ among groups; serum PTH levels rose from 136 ± 38 to 342 ± 140 pg/ml in AD and from 691 ± 99 to 869 ±121 pg/ml in OF. Maximum PTH levels were 322 ± 42% of baseline values in AD but only 146 ± 9.7% of baseline in OF (P
Patrick C. D'haese - One of the best experts on this subject based on the ideXlab platform.
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Effects of efficient Phosphate Binding on bone in chronic renal failure rats.
Renal Failure, 2009Co-Authors: Geert J. Behets, Mareille Gritters, Geert Dams, Marc E. De Broe, Patrick C. D'haeseAbstract:Background. We recently reported that administration of high doses of lanthanum carbonate (1000 mg/kg/day) to chronic renal failure (CRF) rats can result in a mineralization defect. Our results suggested, however, that the impaired mineralization was not due to a direct toxic action of lanthanum on the bone, but rather was an indirect consequence of a Phosphate depletion resulting from the compound's high Phosphate-Binding capacity. To further substantiate these results, in the present study, the effects of lanthanum carbonate on bone were compared to the effects of sevelamer, a nonabsorbed, non-metal-containing polymeric Phosphate-Binding Agent. Methods. Male Wistar rats underwent a 5/6th nephrectomy to induce chronic renal failure, after which they were treated with either sevelamer (500 or 1000 mg/kg/day) or lanthanum carbonate (1000 mg/kg/day) by oral gavage for 12 weeks. Results. CRF animals treated with either sevelamer (500 or 1000 mg/kg/day) or lanthanum carbonate (1000 mg/kg/day) developed a phos...
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Management of hyperPhosphatemia in patients with end-stage renal disease: focus on lanthanum carbonate
International Journal of Nephrology and Renovascular Disease, 2009Co-Authors: Veerle P. Persy, Geert J. Behets, Marc E. De Broe, Patrick C. D'haeseAbstract:Elevated serum Phosphate levels as a consequence of chronic kidney disease (CKD) contribute to the increased cardiovascular risk observed in dialysis patients. Protein restriction and dialysis fail to adequately prevent hyperPhosphatemia, and in general treatment with oral Phosphate Binding Agents is necessary in patients with advanced CKD. Phosphate plays a pivotal role in the development of vascular calcification, one of the factors contributing to increased cardiovascular risk in CKD patients. Treatment of hyperPhosphatemia with standard calcium-based Phosphate binders and vitamin D compounds can induce hypercalcemic episodes, increase the Ca × PO(4) product and thus add to the risk of ectopic mineralization. In this review, recent clinical as well as experimental data on lanthanum carbonate, a novel, non-calcium, non-resin Phosphate Binding Agent are summarized. Although lanthanum is a metal cation no aluminium-like toxicity is observed since the bioavailability of lanthanum is extremely low and its metabolism differs from that of aluminium. Clinical studies now document the absence of toxic effects of lanthanum for up to 6 years of follow-up. The effects of lanthanum on bone, vasculature and brain are discussed and put in perspective with lanthanum pharmacokinetics.
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Localization of lanthanum in bone of chronic renal failure rats after oral dosing with lanthanum carbonate
Kidney International, 2005Co-Authors: Geert J. Behets, Marc E. De Broe, Steven C. Verberckmoes, Line Oste, An R. Bervoets, Murielle Salomé, Alan G. Cox, John Denton, Patrick C. D'haeseAbstract:Localization of lanthanum in bone of chronic renal failure rats after oral dosing with lanthanum carbonate. Background Lanthanum carbonate has been shown to be a safe, effective Phosphate-Binding Agent. We have shown that an impaired mineralization in chronic renal failure rats treated with high doses of lanthanum carbonate develops secondary to Phosphate depletion and is therefore pharmacologically mediated rather than a direct effect of lanthanum on bone. Although bulk bone lanthanum concentrations are low, it is important to consider the localization within a given tissue. Methods Using the scanning x-ray micro-fluorescence set-up at beamline ID21 of the European Synchrotron Radiation Facility, calcium and lanthanum distributions in bone samples were mapped. Results In chronic renal failure rats loaded orally with lanthanum carbonate (12 weeks) (2000 mg/kg/day), bulk bone lanthanum concentrations reached values up to 5 μg/g wet weight. Lanthanum could be demonstrated at the edge of the mineralized bone, at both actively mineralizing and quiescent sites, independent of the type of bone turnover. In the presence of hyperparathyroid bone disease, lanthanum was also distributed throughout the mineralized trabecular bone. No correlation with the presence of osteoid, or the underlying bone pathology could be demonstrated. After a 2- or 4-week washout period before sacrifice, lanthanum localization did not change significantly. Conclusion The comparable localization of lanthanum in different types of bone turnover, and the unchanged localization after washout and consequent disappearance of the mineralization defect, indicates no relationship between the localization of lanthanum in bone and the presence of a mineralization defect.
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Improving outcomes in hyperphosphataemia.
Nephrology dialysis transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2004Co-Authors: Marc E. De Broe, Patrick C. D'haeseAbstract:Preclinical studies have shown that lanthanum has a very high Phosphate-Binding capacity at gastrointestinal pH, while clinical trials have shown lanthanum carbonate to be an effective, well-tolerated Phosphate binder for the treatment of hyperphosphataemia in patients with end-stage renal disease. Optimization of bone health is an important issue in these patients, and, based on theoretical grounds, there have been concerns that lanthanum will have toxic effects on bone similar to those of aluminium. However, compared with aluminium, absorption of lanthanum is extremely low and lanthanum treatment is not associated with systemic toxicity. In addition, unlike aluminium, elimination of lanthanum is not through the kidney, but mainly takes place via the biliary route and is, therefore, independent of renal function. This implies that patients with chronic renal failure are not at an increased risk for accumulation of the element, compared with patients with normal renal function. In animal studies, no adverse effects on bone were seen in healthy animals receiving lanthanum carbonate. In 5/6th nephrectomized rats, very high doses of lanthanum (1000-2000 mg/kg) affected bone mineralization. This was not due to a direct toxic effect on bone, but was secondary to Phosphate depletion induced by lanthanum and, as with any gastro-intestinal Phosphate-Binding Agent, can be reversed with a Phosphate-supplemented diet. In a phase III clinical trial, bone biopsies were taken from dialysis patients at baseline and after 1 year of treatment with either lanthanum carbonate (median dose, 1250 mg/day) or calcium carbonate (median dose, 2000 mg/day). Patients treated with lanthanum carbonate for 1 year did not experience any of the aluminium-like toxic effects on bone expressed as either osteomalacia or adynamic bone disease.