The Experts below are selected from a list of 1134 Experts worldwide ranked by ideXlab platform
Alastair J Hutchison - One of the best experts on this subject based on the ideXlab platform.
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long term mortality and bone safety in patients with end stage renal disease receiving Lanthanum Carbonate
Nephron, 2018Co-Authors: Alastair J Hutchison, Andrew Whelton, Ravi Thadhani, Heinrich Achenbach, Andrea Vergani, Gillian HallAbstract:Background/Aims: This post-marketing observational study assessed the long-term safety of Lanthanum Carbonate (LaC) in US patients with end-stage renal disease (NCT00567723). Methods: Patients (≥18 years old) undergoing dialysis, who had Medicare as their primary healthcare payer, and records in the United States Renal Data System were followed-up for 5 years. Patients who had received LaC for at least 12 consecutive weeks formed the exposed cohort. During the same time period, patients who had undergone dialysis for at least 12 consecutive weeks and had been treated with any other phosphate binder formed the primary comparator cohort. A historical cohort was also evaluated. Primary outcomes were all-cause mortality, and time to and incidence of first bone-fracture event requiring hospitalization. Secondary outcomes were time to first occurrence of and incidence of specific gastrointestinal (GI) disease, liver disease, malignancy, and major infectious episode requiring hospitalization. Results: 2,026 and 8,094 patients were included in the exposed and primary comparator cohorts, respectively. A Cox proportional hazards model showed that patients receiving LaC were not at increased risk of all-cause mortality (adjusted hazard ratio 0.94; 95% CI 0.88–1.01; p = 0.078), bone fractures (0.86; 0.71–1.05; p = 0.130), specific GI disease (0.86; 0.76–0.97; p = 0.015), liver disease (0.88; 0.70–1.09; p = 0.236), malignancy (0.85; 0.54–1.34; p = 0.496), or major infectious episodes (0.87; 0.80–0.94; p < 0.001) requiring hospitalization compared with primary comparator patients. Conclusions: LaC was not associated with increased risk of mortality, bone fractures, or any secondary outcome.
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Lanthanum Carbonate safety data after 10 years
Nephrology, 2016Co-Authors: Alastair J Hutchison, Rosamund Wilson, Svetlana Garafola, John Brian CopleyAbstract:Despite 10 years of post-marketing safety monitoring of the phosphate binder Lanthanum Carbonate, concerns about aluminium-like accumulation and toxicity persist. Here, we present a concise overview of the safety profile of Lanthanum Carbonate and interim results from a 5-year observational database study (SPD405-404; ClinicalTrials.gov identifier: NCT00567723). The pharmacokinetic paradigms of Lanthanum and aluminium are different in that Lanthanum is minimally absorbed and eliminated via the hepatobiliary pathway, whereas aluminium shows appreciable absorption and is eliminated by the kidneys. Randomised prospective studies of paired bone biopsies revealed no evidence of accumulation or toxicity in patients treated with Lanthanum Carbonate. Patients treated with Lanthanum Carbonate for up to 6 years showed no clinically relevant changes in liver enzyme or bilirubin levels. Lanthanum does not cross the intact blood–brain barrier. The most common adverse effects are mild/moderate nausea, diarrhoea and flatulence. An interim Kaplan–Meier analysis of SPD405-404 data from the United States Renal Data System revealed that the median 5-year survival was 51.6 months (95% CI: 49.1, 54.2) in patients who received Lanthanum Carbonate (test group), 48.9 months (95% CI: 47.3, 50.5) in patients treated with other phosphate binders (concomitant therapy control group) and 40.3 months (95% CI: 38.9, 41.5) in patients before the availability of Lanthanum Carbonate (historical control group). Bone fracture rates were 5.9%, 6.7% and 6.4%, respectively. After more than 850 000 person-years of worldwide patient exposure, there is no evidence that Lanthanum Carbonate is associated with adverse safety outcomes in patients with end-stage renal disease.
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Lanthanum Carbonate treatment for up to 6 years is not associated with adverse effects on the liver in patients with chronic kidney disease stage 5 receiving hemodialysis
Clinical Nephrology, 2009Co-Authors: Alastair J Hutchison, M E Barnett, R Krause, J T C Kwan, G A SiamiAbstract:Aims: The efficacy and tolerability of the phosphate binder, Lanthanum Carbonate, have been evaluated in long-term comparative studies and subsequent open-label extensions. Animal studies show that Lanthanum has a very low bioavailability and absorbed Lanthanum is primarily excreted in bile. A specified subset of data from four Phase III clinical trials and subsequent extension studies is presented, in order to assess the effects of Lanthanum Carbonate on the liver. Methods and materials: Hepatic biochemical tests for alanine transaminase, aspartate aminotransferase, alkaline phosphatase and bilirubin were performed. Adverse events classified as "liver and biliary system events" were recorded. Results: In the four initial clinical trials, Lanthanum Carbonate was not associated with any adverse changes in transaminases or bilirubin. The incidence and nature of adverse events associated with the liver during Lanthanum Carbonate treatment was similar to that in the comparator groups. For patients who enrolled into the subsequent long-term follow-up study (up to 6 years of treatment), changes in transaminases were not clinically relevant and mean values were similar to those observed in the earlier trials. Overall, there was no increase in the incidence of adverse events associated with the liver reported after up to 6 years of treatment when compared with the results of the initial studies. Conclusions: There was no evidence of adverse effects of Lanthanum Carbonate on the liver in patients who received treatment for up to 6 years.
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switching to Lanthanum Carbonate monotherapy provides effective phosphate control with a low tablet burden
Nephrology Dialysis Transplantation, 2008Co-Authors: Alastair J Hutchison, M LavilleAbstract:Background. Despite recognized risks associated with hyperphosphataemia in patients with chronic kidney disease (CKD) Stage 5 on dialysis, the achievement of target levels of serum phosphate is poor. It is likely that this is partly due to poor adherence by patients to their phosphate-binder treatment regimens, which often comprise large daily tablet burdens. Methods. In this multicentre, open-label trial, patients on a stable dialysis regimen were screened while receiving phosphate-binder therapy, then entered into a washout phase. Patients with serum phosphate > 1.78 mmol/L after washout entered into the main 12-week treatment phase (N = 367), during which they were treated to target [Kidney Disease Outcomes Quality Initiative (K/DOQI)]: 1.13– 1.78 mmol/L; 3.5–5.5 mg/dL) with Lanthanum Carbonate monotherapy. Efficacy variables included serum phosphate levels and the percentage of patients with serum phosphate control. Safety and tolerability assessments were also conducted. Results. Mean serum phosphate levels were significantly reduced following 12 weeks of Lanthanum Carbonate monotherapy versus previous phosphate-binder therapy. The mean number of phosphate-binder tablets being taken per day at screening was 7.6, but during treatment with Lanthanum Carbonate, most patients were taking doses of up to 3000 mg/day, achievable with 3 × 1000 mg tablets per day (maximum of 6). Conclusion. These findings suggest that Lanthanum Carbonate monotherapy offers effective control of serum phosphate and, due to a low tablet burden, may help to simplify the management of hyperphosphataemia in patients with CKD Stage 5.
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long term efficacy and safety profile of Lanthanum Carbonate results for up to 6 years of treatment
Nephron Clinical Practice, 2008Co-Authors: Alastair J Hutchison, Edwina M Barnett, Rolfdieter Krause, Jonathan T C Kwan, Ghodrat A SiamiAbstract:Background/Aims: Lanthanum Carbonate (LC, FOSRENOL®) is an effective phosphate binder for which tolerability and a safety profile have been reported in haemodialysis patients. Patients from previous studies entered a 2-year extension, enabling assessment of efficacy and safety for up to 6 years of LC monotherapy. Methods: Patients from four previous trials entered this study. Results: Ninety-three patients started the extension, with 22 entering a sixth year of LC treatment. Two-thirds of all patients received LC doses of 2,250 or 3,000 mg/day. Reductions in serum phosphate and calcium × phosphate product were maintained for up to 6 years. There were no new or unexpected adverse events (AEs), and no increase in the incidence of events with increasing treatment exposure. Over the complete duration of therapy, treatment-related AEs occurred in 25.8% of patients and were primarily gastrointestinal in nature. No clinically relevant changes in liver function tests were observed and there was no evidence of adverse effects on the liver, bone or the central nervous system. Conclusions: LC monotherapy was effective and well tolerated for up to 6 years with no evidence of safety concerns or increased frequency of AEs.
Paul J Chen - One of the best experts on this subject based on the ideXlab platform.
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great enhancement in phosphate uptake onto Lanthanum Carbonate grafted microfibrous composite under a low voltage electrostatic field
Chemosphere, 2021Co-Authors: Yi Yang, Kok Yuen Koh, Huiping Zhang, Ying Yan, Haoxin Huang, Paul J ChenAbstract:Abstract Removal of phosphorus from water via cost-effective measures becomes important for water industry mainly due to eutrophication in waterbody. In our lab, a novel Lanthanum Carbonate-microfibrous composite (LC-MC) with good performance was previously synthesized for the removal of phosphorus. In this study, we further improved our technology by applying the electrostatic field (direct current, DC) to the adsorption system. It was showed that the applied DC can greatly improve the adsorption of phosphate in particular the adsorption capacity. Better removal was seen in the pH range of 5–9 at a higher temperature. The maximum adsorption capacity of 47.57 mg- PO 4 3 − g−1 was achieved, which was 1.4 times of that operated in the absence of applied DC. The adsorption equilibrium was established at the contact time of 240 min; the adsorption history was well described by the intraparticle surface diffusion model. The negative effect from oxygen-containing anions on the phosphate uptake followed the decreasing sequence of: humic acid > Carbonate > nitrate > sulfate; on the other hand, the halogen anions had almost no influence on it. Finally, the mechanism study by XPS, XRD, and IR demonstrated that the ligand exchange played an important role in the electro-assisted phosphate uptake process.
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an innovative Lanthanum Carbonate grafted microfibrous composite for phosphate adsorption in wastewater
Journal of Hazardous Materials, 2020Co-Authors: Yi Yang, Kok Yuen Koh, Huiping Zhang, Ying Yan, Paul J ChenAbstract:Abstract Excessive presence of phosphorus in waters can cause eutrophication, a global unsolved environmental problem that has caused harmful effects to our eco-system and the source of our drinking water. In the study presented in this paper, a novel Lanthanum Carbonate grafted microfibrous composite (LC–MC) adsorbent was synthesized aiming at removing large amount of phosphate in wastewater efficiently. An optimized LC–MC was firstly prepared. The most suitable pH for the phosphate uptake was pH 7 to 9. The adsorption showed similar behavior in a wide range of ionic strength. The presence of co-existing anions was proved to have a less significant effect on the removal. The adsorption isotherm data were better fitted by the Freundlich isotherm than the Langmuir isotherm. The equilibrium was reached at about 300 min of contact time. 80 % of original adsorption capacity can be achieved even after 5 cycles of adsorption- desorption operations, indicating great regenerative performance of the adsorbent. The adsorption mechanism study showed that the ligand exchange played a key role during the phosphate adsorption.
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hydrothermally synthesized Lanthanum Carbonate nanorod for adsorption of phosphorus material synthesis and optimization and demonstration of excellent performance
Chemical Engineering Journal, 2020Co-Authors: Kok Yuen Koh, Sui Zhang, Paul J ChenAbstract:Abstract Eutrophication has caused severe damages to water environment, due to excessive release of nutrients (phosphorus and nitrogen). Effective removal of phosphorus is of great importance in prevention of eutrophication. In this article, we report a hydrothermal synthesized Lanthanum Carbonate (LC) nanorod for removal of phosphate. The concentration of urea, temperature and time were first optimized so as to obtain the best LC nanorod for the removal. It was showed that the best adsorption was obtained at pH 3 and pH 5 when pH was not controlled and was controlled, respectively. The LC worked well in pH 3–8 for the phosphate removal. The experimental data were fitted well by Langmuir isotherm; the maximum adsorption capacities of 312.5 and 303.03 mg/g were found at pH 5 and 7, respectively. The adsorption equilibrium time was 5 h; the adsorption history was well described by the pseudo-second-order equation. High ionic strength of solution (up to 1-M NaNO3) and existence of competitive substances (30–100-mg/L) showed insignificant impacts on the phosphate uptake. The spent adsorbent can be regenerated and reused satisfactorily. The mechanism study revealed that the adsorption was associated with ion exchange between Carbonate and phosphate ions. Our study demonstrated that the LC nanorod was a potential adsorbent for the phosphate removal.
Stephen J.p. Damment - One of the best experts on this subject based on the ideXlab platform.
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long term treatment with Lanthanum Carbonate reduces mineral and bone abnormalities in rats with chronic renal failure
Nephrology Dialysis Transplantation, 2011Co-Authors: Stephen J.p. Damment, Roger Secker, Victor Shen, Victor Lorenzo, Mariano RodriguezAbstract:Background. Lanthanum Carbonate (FOSRENOL®, Shire Pharmaceuticals) is an effective non-calcium, non-resin phosphate binder for the treatment of hyperphosphataemia in patients with chronic kidney disease (CKD). In this study, we used a rat model of chronic renal failure (CRF) to examine the long-term effects of controlling serum phosphorus with Lanthanum Carbonate treatment on the biochemical and bone abnormalities associated with CKD–mineral and bone disorder (CKD–MBD). Methods. Rats were fed a normal diet (normal renal function, NRF), or a diet containing 0.75% adenine for 3 weeks to induce CRF. NRF rats continued to receive normal diet plus vehicle or normal diet supplemented with 2% (w/w) Lanthanum Carbonate for 22 weeks. CRF rats received a diet containing 0.1% adenine, with or without 2% (w/w) Lanthanum Carbonate. Blood and urine biochemistry were assessed, and bone histomorphometry was performed at study completion. Results. Treatment with 0.75% adenine induced severe CRF, as demonstrated by elevated serum creatinine. Hyperphosphataemia, hypocalcaemia, elevated calcium × phosphorus product and secondary hyperparathyroidism were evident in CRF + vehicle animals. Treatment with Lanthanum Carbonate reduced hyperphosphataemia and secondary hyperparathyroidism in CRF animals (P < 0.05), and had little effect in NRF animals. Bone histomorphometry revealed a severe form of bone disease with fibrosis in CRF + vehicle animals; Lanthanum Carbonate treatment reduced the severity of the bone abnormalities observed, particularly woven bone formation and fibrosis. Conclusions. Long-term treatment with Lanthanum Carbonate reduced the biochemical and bone abnormalities of CKD–MBD in a rat model of CRF.
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pharmacology of the phosphate binder Lanthanum Carbonate
Renal Failure, 2011Co-Authors: Stephen J.p. DammentAbstract:Studies were conducted to compare the phosphate-binding efficacy of Lanthanum Carbonate directly with other clinically used phosphate binders and to evaluate any potential adverse pharmacology. To examine the phosphate-binding efficacy, rats with normal renal function and chronic renal failure received Lanthanum Carbonate, aluminum hydroxide, calcium Carbonate, or sevelamer hydrochloride in several experimental models. Lanthanum Carbonate and aluminum hydroxide markedly increased excretion of [32P]-phosphate in feces and reduced excretion in urine in rats with normal renal function (p < 0.05), indicating good dietary phosphate-binding efficacy. In rats with chronic renal failure, Lanthanum Carbonate and aluminum hydroxide reduced urinary phosphate excretion to a greater degree and more rapidly than calcium Carbonate, which in turn was more effective than sevelamer hydrochloride. The potential to induce adverse pharmacological effects was assessed systematically in mice, rats, and dogs with normal renal function using standard in vivo models. There was no evidence of any adverse secondary pharmacological effects of Lanthanum Carbonate on the central nervous, cardiovascular, respiratory, or gastrointestinal systems. These studies indicate that Lanthanum Carbonate is the more potent of the currently available dietary phosphate binders. No adverse secondary pharmacological actions were observed in vivo in a systematic evaluation at high doses.
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a model of the kinetics of Lanthanum in human bone using data collected during the clinical development of the phosphate binder Lanthanum Carbonate
Clinical Pharmacokinectics, 2008Co-Authors: Felix Bronner, Michael Pennick, Boris M Slepchenko, Stephen J.p. DammentAbstract:Objective: Lanthanum Carbonate (Fosrenol®) is a non-calcium phosphate binder that controls hyperphosphataemia without increasing calcium intake above guideline targets. The biological fate and bone load of Lanthanum were modelled with the aid of a four-compartment kinetic model, analogous to that of calcium.
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clinical pharmacokinetics of the phosphate binder Lanthanum Carbonate
Clinical Pharmacokinectics, 2008Co-Authors: Stephen J.p. Damment, Michael PennickAbstract:Lanthanum Carbonate is considered to be the most potent of a new generation of noncalcium phosphate binders used to treat hyperphosphataemia in chronic kidney disease (CKD), a condition associated with progressive bone and cardiovascular pathology and a markedly elevated risk of death. Its phosphate-binding action involves ionic binding and precipitation of insoluble complexes within the lumen of the intestine, thereby preventing absorption of dietary phosphate. While pharmacokinetics have little relevance to the efficacy of Lanthanum Carbonate, they are of fundamental importance when it comes to evaluating safety. When administered as Lanthanum Carbonate, the oral bioavailability of Lanthanum is low (∼0.001%). The small absorbed fraction is excreted predominantly in bile, with less than 2% being eliminated by the kidneys. Predictably, therefore, plasma exposure and pharmacokinetics have been shown to be similar in healthy human volunteers and CKD stage 5 patients. With almost complete plasma protein binding, free Lanthanum concentrations in patients at steady state are <3 pg/mL. These properties greatly reduce systemic exposure, tissue deposition and the potential for adverse effects. While Lanthanum has a variety of calcium-like actions in vitro, there is little or no evidence that these occur in vivo. This paradox is explained by the very low concentrations of circulating free Lanthanum ions, which are many orders of magnitude lower than reported effect concentrations in vitro. Safety pharmacology and toxicology evaluations have failed to reveal any significant calcium-like actions in vivo, despite inclusion of high intravenous doses in some cases. Lanthanum Carbonate has a low propensity to cause systemic drug interactions due to its poor absorption. However, the higher concentrations present in the gastrointestinal tract can form chelates with some drugs, such as fluoroquinolones, and reduce their absorption. The improved understanding of the pharmacokinetics of Lanthanum that has emerged in recent years has helped to explain why the myriad of calcium-like effects described in vitro for Lanthanum have little if any relevance in vivo. The pharmacokinetic investigations of Lanthanum Carbonate formed an important part of the stringent premarketing safety assessment process and have been influential in reassuring both regulators and physicians that the agent can be used safely and effectively in this vulnerable dialysis population.
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clinical pharmacokinetics of the phosphate binder Lanthanum Carbonate
Clinical Pharmacokinectics, 2008Co-Authors: Stephen J.p. Damment, Michael PennickAbstract:Lanthanum Carbonate is considered to be the most potent of a new generation of noncalcium phosphate binders used to treat hyperphosphataemia in chronic kidney disease (CKD), a condition associated with progressive bone and cardiovascular pathology and a markedly elevated risk of death. Its phosphate-binding action involves ionic binding and precipitation of insoluble complexes within the lumen of the intestine, thereby preventing absorption of dietary phosphate. While pharmacokinetics have little relevance to the efficacy of Lanthanum Carbonate, they are of fundamental importance when it comes to evaluating safety. When administered as Lanthanum Carbonate, the oral bioavailability of Lanthanum is low (∼0.001%). The small absorbed fraction is excreted predominantly in bile, with less than 2% being eliminated by the kidneys. Predictably, therefore, plasma exposure and pharmacokinetics have been shown to be similar in healthy human volunteers and CKD stage 5 patients. With almost complete plasma protein binding, free Lanthanum concentrations in patients at steady state are <3 pg/mL. These properties greatly reduce systemic exposure, tissue deposition and the potential for adverse effects. While Lanthanum has a variety of calcium-like actions in vitro, there is little or no evidence that these occur in vivo. This paradox is explained by the very low concentrations of circulating free Lanthanum ions, which are many orders of magnitude lower than reported effect concentrations in vitro. Safety pharmacology and toxicology evaluations have failed to reveal any significant calcium-like actions in vivo, despite inclusion of high intravenous doses in some cases.
William F Finn - One of the best experts on this subject based on the ideXlab platform.
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Lanthanum Carbonate reduces phosphorus burden in patients with ckd stages 3 and 4 a randomized trial
Clinical Journal of The American Society of Nephrology, 2009Co-Authors: Stuart M Sprague, Hanna E Abboud, Ping Qiu, Matthew Dauphin, Pinggao Zhang, William F FinnAbstract:Background and objectives: Lanthanum Carbonate (FOSRENOL®, Shire Pharmaceuticals) is an effective noncalcium, nonresin phosphate binder for the control of hyperphosphatemia in chronic kidney disease (CKD) stage 5 patients undergoing dialysis. Design, setting, participants and measurements: A Phase 2, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of Lanthanum Carbonate in CKD stage 3 and 4 patients. Of 281 patients screened, 121 were randomized (2:1) to Lanthanum Carbonate or placebo (80 versus 41). The modified intent-to-treat population included 90 patients (56 versus 34); 71 (43 versus 28) completed the study. After run-in, when any current phosphate binders were discontinued and dietary counseling reinforced, patients with serum phosphorus >4.6 mg/dl received Lanthanum Carbonate (titrated up to 3000 mg/d) or matching placebo for 8 wk. Results: At the end of treatment, 25 (44.6%) versus nine (26.5%) patients had serum phosphorus ≤4.6 mg/dl (difference 18.1%, P = 0.12) in the Lanthanum Carbonate and placebo groups, respectively. Statistically significant differences were observed between groups in change from baseline to end of treatment for serum phosphorus (P = 0.02), intact parathyroid hormone (P = 0.02), and urinary phosphorus excretion (P = 0.04). The safety profile and tolerability of Lanthanum Carbonate were similar to that of placebo. Conclusions: Because <1% of phosphorus is in the extracellular fluid, serum measurements may not accurately reflect total body burden in patients with CKD stages 3 and 4. However, Lanthanum Carbonate is an effective phosphate binder in this patient population, with a safety profile and tolerability similar to that of placebo.
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cognitive function in stage 5 chronic kidney disease patients on hemodialysis no adverse effects of Lanthanum Carbonate compared with standard phosphate binder therapy
Kidney International, 2007Co-Authors: P Altmann, M E Barnett, William F FinnAbstract:Patients with Stage 5 chronic kidney disease who have hyperphosphatemia require treatment with phosphate binders to lower serum phosphorus levels. Existing binders are effective but may be associated with important safety disadvantages. Lanthanum Carbonate is a phosphate binder with demonstrated efficacy, safety, and tolerability in clinical trials. Changes in cognitive function were evaluated over time using the Cognitive Drug Research computerized cognitive assessment system (Simple Reaction Time, Digit Vigilance Task, Choice Reaction Time, Numeric Working Memory, and Delayed Picture Recognition) in 360 hemodialysis patients who were enrolled in a 2-year, multicenter, comparative study of Lanthanum Carbonate versus standard therapy. A decline in cognitive function from baseline was observed in both groups. The deterioration in cognitive function was similar in both the Lanthanum Carbonate and standard therapy groups. One parameter – Numeric Working Memory – showed a statistically significant between-group difference in favor of Lanthanum Carbonate ( P =0.02). Given the magnitude of the changes, however, and the differences that were observed at baseline between treatment groups, the clinical significance of this difference is doubtful. This study demonstrates that cognitive function deteriorates in hemodialysis patients over a 2-year time period. Use of Lanthanum Carbonate as a phosphate binder does not adversely affect cognitive function compared with standard therapy.
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a long term open label extension study on the safety of treatment with Lanthanum Carbonate a new phosphate binder in patients receiving hemodialysis
Current Medical Research and Opinion, 2005Co-Authors: William F FinnAbstract:ABSTRACTBackground: Lanthanum Carbonate, a new phosphate binder, is effective in reducing serum phosphorus levels in patients with end-stage renal disease. A 1-year extension study to two randomized controlled studies was conducted to evaluate the long-term safety of Lanthanum Carbonate in patients who received hemodialysis.Research design and methods: Patients from two previous Lanthanum Carbonate studies were eligible to continue treatment in a 1-year open-label extension. A total of 77 patients (N = 77; 11 from Study 1, 66 from Study 2) were enrolled in this extension. The mean age of patients was 60.9 years (SD ± 12.5 years); 65% were male and 35% were female. All patients received Lanthanum Carbonate at the optimal dose for phosphorus control, determined in their previous study. Safety and tolerability were assessed by monitoring adverse events, laboratory parameters, and vital signs. The number of patients who maintained serum phosphorus levels at ≤ 5.9 mg/dL (1.9 mmol/L) was recorded, along with se...
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efficacy and safety of Lanthanum Carbonate for reduction of serum phosphorus in patients with chronic renal failure receiving hemodialysis
Clinical Nephrology, 2004Co-Authors: William F Finn, Melanie S Joy, G HladikAbstract:BACKGROUND Lanthanum Carbonate is a highly effective phosphate binder with significant potential as a treatment for hyperphosphatemia in patients with end-stage renal disease (ESRD). Here, the results of a placebo-controlled, dose-ranging study are presented. METHODS 196 patients (> or = 18 years) receiving hemodialysis for at least 6 months entered a 1- to 3-week, single-blind, placebo run-in phase. Of these, 145 patients were randomized to a double-blind phase in which they received placebo or Lanthanum Carbonate in daily Lanthanum doses of 225, 675, 1,350 or 2,250 mg for 6 weeks. Serum levels of phosphorus, calcium and parathyroid hormone, and adverse events were monitored throughout the study. RESULTS The intent-to-treat analysis (n = 144) showed significant dose-related reductions in serum phosphorus at Lanthanum doses of 675, 1,350 and 2,250 mg. After 6 weeks of treatment, phosphorus levels were significantly lower in the Lanthanum groups receiving 1,350 mg/day and 2,250 mg/day, compared with the placebo group (respective changes from randomization: -0.95 +/- 1.39 mg/dl (-0.31 +/- 0.45 mmol/l), -1.13 +/- 2.01 mg/dl (-0.36 +/- 0.65 mmol/l), 0.75 +/- 1.47 mg/dl (0.24 +/- 0.47 mmol/l), p < 0.001). Significant reductions in serum phosphorus, compared with placebo, occurred in the Lanthanum 1,350 mg/day group from the second week of treatment and in the 2,250 mg/day group from the first week of treatment. Adverse events were mainly gastrointestinal (e.g. nausea and vomiting). Treatment-related adverse events occurred in 39% of patients treated with Lanthanum Carbonate and 44% of the placebo group. CONCLUSION Lanthanum Carbonate is an effective and well-tolerated agent for the short-term treatment of hyperphosphatemia in patients with ESRD.
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randomized double blind placebo controlled dose titration phase iii study assessing the efficacy and tolerability of Lanthanum Carbonate a new phosphate binder for the treatment of hyperphosphatemia
American Journal of Kidney Diseases, 2003Co-Authors: William F FinnAbstract:Abstract Background: Lanthanum Carbonate is a novel, non-calcium, non-aluminum phosphate binder under evaluation for the treatment of hyperphosphatemia in end-stage renal disease (ESRD) patients receiving either hemodialysis or continuous ambulatory peritoneal dialysis. Methods: This 16-week study assessed the control of serum phosphorus with Lanthanum Carbonate, and its effects on serum calcium, calcium × phosphorus product, and parathyroid hormone (PTH). Hemodialysis patients ≥18 years old entered into a 1- to 3-week washout period during which serum phosphorus levels rose to >5.9 mg/dL (1.90 mmol/L). In total, 126 patients were titrated with Lanthanum Carbonate at doses containing 375, 750, 1,500, 2,250, or 3,000 mg/d elemental Lanthanum, given in divided doses with meals over a 6-week period, to achieve serum levels ≤5.9 mg/dL. By the end of dose titration, 11/126 (9%) patients received ≤750 mg/d of Lanthanum, 25 (20%) received 1,500 mg/d, 37 (29%) received 2,250 mg/d, and 53 (42%) received 3,000 mg/d. Following titration, patients were randomized to receive either Lanthanum Carbonate or placebo during a 4-week, double-blind maintenance phase. Results: At the study endpoint, the mean difference in serum phosphorus between the Lanthanum Carbonate and placebo treatment arms was 1.91 mg/dL (0.62 mmol/L) ( P P P Conclusion: Lanthanum Carbonate is an effective and well-tolerated agent for the treatment of hyperphosphatemia in patients with ESRD.
Geert J. Behets - One of the best experts on this subject based on the ideXlab platform.
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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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does the phosphate binder Lanthanum Carbonate affect bone in rats with chronic renal failure
Journal of The American Society of Nephrology, 2004Co-Authors: Geert J. Behets, Stephen J.p. Damment, Sven R Vercauteren, Roger Bouillon, Geert Dams, Marc E. De Broe, Patrick C DhaeseAbstract:ABSTRACT. Adequate control of phosphate levels remains an important issue in patients with chronic renal failure (CRF). Lanthanum Carbonate has been proposed as a new phosphate binder. Previous studies have shown a high phosphate binding capacity (>97%) and low gastrointestinal absorption of Lanthanum, without serious toxic side effects in the presence of a normal renal function (NRF). Because of Lanthanum’s physicochemical resemblance to calcium, the possible effects of it on bone have to be considered. The aim of this study was to investigate the effects of Lanthanum Carbonate on bone histology in NRF and CRF rats after oral administration of the compound with doses of 100, 500, or 1000 mg/kg per d for 12 wk. Bone histomorphometry showed that CRF animals that received vehicle developed secondary hyperparathyroidism. Urinalysis of Lanthanum-loaded CRF animals showed a dose-dependent decrease in urinary phosphorus excretion, which was clearly more pronounced in the CRF groups compared with NRF animals. Phosphatemia, however, remained normal. Lanthanum Carbonate administration induced a dose-dependent decrease in bone formation rate and increase in osteoid area in CRF animals. Three of seven animals in the CRF-1000 group and one of eight animals in the NRF-100 group were classified as having a mineralization defect. The number of cuboidal osteoblasts, however, was not affected, indicating that bone changes were not due to a toxic effect of Lanthanum on the osteoblast. Furthermore, Lanthanum concentrations in the femur remained low and did not correlate with histomorphometric parameters. These findings suggest that the administration of high doses of phosphate binder (1000 mg/kg per d Lanthanum Carbonate), in combination with decreased 25-(OH) vitamin D 3 in the uremic state, resulted in phosphate depletion and followed by an increased mobilization of phosphorus out of bone and/or reduced incorporation into bone. There was no evidence that Lanthanum had a direct toxic effect on osteoblasts.
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Lanthanum Carbonate a new phosphate binder
Current Opinion in Nephrology and Hypertension, 2004Co-Authors: Geert J. Behets, Patrick C Dhaese, Steven C. Verberckmoes, Marc E. De BroeAbstract:Purpose of reviewHyperphosphatemia remains an important aspect in the management of end-stage renal disease patients. Consequently, there is a need for new, efficient and well-tolerated phosphate binders. In this review, a new phosphate-binding drug, Lanthanum Carbonate, with an attractive preclinic
