Receiving Lanthanum Carbonate Research Articles

The Pharmacological Effect and Mechanism of Lanthanum Hydroxide on Vascular Calcification Caused by Chronic Renal Failure Hyperphosphatemia.

ObjectiveThe present work aimed to explore the efficacy of lanthanum hydroxide in managing the vascular calcification induced by hyperphosphate in chronic renal failure (CRF) as well as the underlying mechanism.MethodsRats were randomly allocated to five groups: normal diet control, CKD hyperphosphatemia model, CKD model treated with lanthanum hydroxide, CKD model receiving lanthanum carbonate treatment, together with CKD model receiving calcium carbonate treatment. The serum biochemical and kidney histopathological parameters were analyzed. The aortic vessels were subjected to Von Kossa staining, CT scan and proteomic analysis. In vitro, the calcium content and ALP activity were measured, and RT-PCR (SM22α, Runx2, BMP-2, and TRAF6) and Western blot (SM22α, Runx2, BMP-2, TRAF6, and NF-κB) were performed.ResultsIn the lanthanum hydroxide group, serum biochemical and kidney histopathological parameters were significantly improved compared with the model group, indicating the efficacy of lanthanum hydroxide in postponing CRF progression and in protecting renal function. In addition, applying lanthanum hydroxide postponed hyperphosphatemia-mediated vascular calcification in CKD. Furthermore, lanthanum hydroxide was found to mitigate vascular calcification via the NF-κB signal transduction pathway. For the cultured VSMCs, lanthanum chloride (LaCl3) alleviated phosphate-mediated calcification and suppressed the activation of NF-κB as well as osteo-/chondrogenic signal transduction. Lanthanum hydroxide evidently downregulated NF-κB, BMP-2, Runx2, and TRAF6 expression.ConclusionLanthanum hydroxide protects against renal failure and reduces the phosphorus level in serum to postpone vascular calcification progression.

Deposition patterns of iatrogenic lanthanum and gadolinium in the human body depend on delivered chemical binding forms

BackgroundRecently, gadolinium from linear GBCAs has been reported to deposit in various regions of the body. Besides gadolinium, other lanthanides are used in medical care. In the current study, we investigated deposition of lanthanum in two patients who received lanthanum carbonate as a phosphate binder due to chronic kidney injury and compared it to additionally found Gd deposition. MethodsTissue specimens of two patients with long-term application of lanthanum carbonate as well as possible GBCA application were investigated. Spatial distribution of gadolinium and lanthanum was determined by quantitative laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging of tissue sections. The deposition of gadolinium and lanthanum in different organs was compared, and the ratio of Gd concentration to La concentration (Gd-to-La-ratio) was investigated on an individual pixel base within the images. ResultsDeposition of Gd and La was found in all investigated tissues of both patients. Gd and La exhibited high spatial correlation for all samples, with the main deposition being located in the middle coat (tunica media) of blood vessels. The Gd-to-La-ratio was similar in the tissues investigated (between 8 ± 4 (mean ± standard deviation) and 10 ± 2), except for the thyroid vasculature and surrounding tissue (90 ± 17) as well as the cerebellum (270 ± 18). Here, the ratio was significantly increased towards higher Gd concentration. ConclusionThe results of this study demonstrate long-term deposition of La and comparable localization of additionally found Gd in various tissues of the body. La deposition was relatively low, considering the total administered amount of lanthanum carbonate of up to 11.5 kg, indicating a low absorption and/or high excretion of lanthanum. However, the total amount of deposited La is significant and raises questions about possible adverse side effects. The ratio-approach allows for the usage of the additionally generated Gd data, without detailed knowledge about possible GBCA applications. The significantly decreased Gd-to-La-ratio in the brain might be explained by the lanthanum being released and taken up as free La3+ ion in the stomach that impedes a crossing of the blood-brain-barrier while the intravenously injected GBCAs might dechelate first when they have already crossed the blood-brain-barrier.

Case of early-stage gastric cancer identified in the gastric mucosa with lanthanum phosphate deposition

Background and study aims A 78-year-old man with Helicobacter pylori infection had been undergoing hemodialysis for chronic renal failure and receiving lanthanum carbonate preparations for 3 years. Endoscopy revealed fine white granular discoloration throughout the stomach, a moderately reddish depression on the lesser curvature of the gastric angle, and white granular discoloration in the surrounding area. A magnified image using narrow-band imaging showed that the depressed part had irregular vascular and pit structures. We established a diagnosis of intramucosal gastric cancer and performed endoscopic submucosal dissection. Histopathological examination revealed a well-differentiated adenocarcinoma that was confined to the mucosa of the depressed area. Moreover, using an electron probe microanalyzer-equipped electron microscope, we found that the degree of lanthanum deposition was lower in the tumor region than in the non-tumor region. Thus, the current case can help in understanding the relationship between lanthanum deposition and early-stage gastric cancer. Because gastric cancers can occur in lanthanum deposit-containing mucosa, esophagogastroduodenoscopy should be used carefully after understanding the characteristics of early- stage gastric cancer in such cases.

Long-Term Mortality and Bone Safety in Patients with End-Stage Renal Disease Receiving Lanthanum Carbonate

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.

Effect of Sucroferric Oxyhydroxide on Fibroblast Growth Factor 23 Levels in Hemodialysis Patients

Objective: This study investigated the effects of sucroferric oxyhydroxide on fibroblast growth factor (FGF)-23 and dose reduction of erythropoiesis-stimulating agents (ESA) and intravenous saccharated ferric oxide in hemodialysis patients. Methods: In this prospective, open-label, parallel-group, multicenter trial involving patients receiving lanthanum carbonate hydrate, eligible patients were randomized to a sucroferric oxyhydroxide group or a control group. Hemoglobin, serum phosphate, FGF-23, iron, and ferritin levels, as well as transferrin saturation, doses of intravenous saccharated ferric oxide and ESA administered, and the erythropoietin responsiveness index (ERI) were monitored for 24 weeks. Results: Sixty-eight eligible patients were allocated to receive sucroferric oxyhydroxide (n = 34) or serve as controls (n = 34). Data for 31 patients in the sucroferric oxyhydroxide group and 32 in the control group were analyzed. Serum phosphate was equally well controlled in both groups. In the sucroferric oxyhydroxide group, intact FGF-23 levels decreased significantly from baseline at the end of the study (p = 0.01) and there was a significant difference compared with the control group (p = 0.035). Required doses of ESA and ERI were significantly reduced in the sucroferric oxyhydroxide group decreased significantly. The dose of intravenous saccharated ferric oxide required in the sucroferric oxyhydroxide group was significantly lower than that at baseline (p = 0.006) and in the control group (p = 0.003). Conclusions: Treatment of hyperphosphatemia with sucroferric oxyhydroxide was effective in patients on hemodialysis, resulting in decreased serum FGF-23 levels and a reduction in the required dose of saccharated ferric oxide.

Nutritional status and survival of maintenance hemodialysis patients receiving lanthanum carbonate.

Hyperphosphatemia and poor nutritional status are associated with increased mortality. Lanthanum carbonate is an effective, calcium-free phosphate binder, but little is known about the long-term impact on mineral metabolism, nutritional status and survival. We extended the follow-up period of a historical cohort of 2292 maintenance hemodialysis patients that was formed in late 2008. We examined 7-year all-cause mortality according to the serum phosphate levels and nutritional indicators in the entire cohort and then compared the mortality rate of the 562 patients who initiated lanthanum with that of the 562 propensity score-matched patients who were not treated with lanthanum. During a mean ± SD follow-up of 4.9 ± 2.3years, 679 patients died in the entire cohort. Higher serum phosphorus levels and lower nutritional indicators (body mass index, albumin and creatinine) were each independently associated with an increased risk of death. In the propensity score-matched analysis, patients who initiated lanthanum had a 23% lower risk for mortality compared with the matched controls. During the follow-up period, the serum phosphorus levels tended to decrease comparably in both groups, but the lanthanum group maintained a better nutritional status than the control group. The survival benefit associated with lanthanum was unchanged after adjustment for time-varying phosphorus or other mineral metabolism parameters, but was attenuated by adjustments for time-varying indicators of nutritional status. Treatment with lanthanum is associated with improved survival in hemodialysis patients. This effect may be partially mediated by relaxation of dietary phosphate restriction and improved nutritional status.

Iron parameters in patients with end-stage renal disease receiving lanthanum carbonate or other non-iron-based phosphate binders: Results from a phase 3, randomized open-label study.

Objectives:The recent availability of iron-based phosphate binders has raised some concerns about iron overload in patients with end-stage renal disease. This study evaluated iron parameters in patients with end-stage renal disease receiving lanthanum carbonate or other non-iron-based phosphate binders.Methods:This analysis used 2-year follow-up data from an open-label, multicentre, randomized, active-controlled, parallel-group, phase 3 trial of lanthanum carbonate (SPD405-307). After a washout period, if patients’ serum phosphate levels exceeded 5.9 mg/dL, they were randomized 1:1 to receive lanthanum carbonate (375–3000 mg/day) or non-iron-based standard therapy during a 6-week dose titration period. Patients achieving control of serum phosphate levels (⩽5.9 mg/dL) received maintenance therapy with lanthanum carbonate or standard therapy for up to 24 months.Results:No clinically relevant changes in mean (standard deviation) iron parameters between the treatment groups (lanthanum carbonate, n = 682; standard therapy, n = 677) from baseline to month 24/final visit were observed: iron (µg/dL), −1.1 (41.8) versus 1.0 (38.7); ferritin (ng/mL), 208.4 (445.1) versus 262.4 (505.5); transferrin saturation (%), 2.8 (18.0) versus 2.8 (17.3); and haemoglobin (g/dL), 0.4 (1.9) versus 0.3 (1.7), respectively (all, p > 0.1). There were no clinically relevant changes in the percentage of patients receiving any anti-anaemic preparation in either treatment group (pre- vs post-randomization: lanthanum carbonate, 94.9% vs 97.8%; standard therapy, 95.1% vs 98.8%, respectively). This is in contrast to the study by Lewis and colleagues, which found significant increases in ferritin and transferrin saturation levels in patients receiving ferric citrate versus active control (calcium acetate and/or sevelamer carbonate) after 52 weeks of therapy. Although serum ferritin and transferrin saturation are the recommended iron indices by the Kidney Disease Outcome Quality Initiative, they are indirect indicators of iron status. Longer-term studies are required to understand fully the potential risks associated with iron overload.Conclusion:No evidence of iron accumulation was found in patients with end-stage renal disease receiving lanthanum carbonate or other non-iron-based binders.

Lanthanum carbonate: safety data after 10 years.

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.

Clinical experiences of bixalomer usage at our hospital.

In 2012, bixalomer was launched as new non-calcium (Ca) containing phosphorus (P) binder, increasing the choices available for the treatment of hyperphosphatemia. In this study, among the maintenance dialysis patients at our hospital, we newly administered bixalomer to 21 patients who were not receiving any P binders, and switched to bixalomer for 13 patients who had been receiving sevelamer hydrochloride and 23 patients who had been receiving lanthanum carbonate. The initial dosage of bixalomer was set as 1500 mg/day for new administration patients and dosage equivalent to that of the previously-used P binder for patients who were switched to bixalomer. The dosage of bixalomer was increased if the effects were insufficient. The serum P, Ca and intact parathyroid hormone concentrations as well as serum pH, HCO3 concentration and base excess were evaluated prior to administering bixalomer, 3 months and 6 months after administering bixalomer. For the group who were newly administered bixalomer, significant reductions in serum P concentrations were seen (P<0.01) and no significant changes were seen in clinical test items that serve as indices for acidosis. For the group who were switched from sevelamer hydrochloride to bixalomer, significant reductions in serum P concentrations were seen (P<0.01) together with significant improvements in acidosis (P<0.01). For the group who were switched from lanthanum carbonate to bixalomer, by increasing the dosage of bixalomer to approximately three times the dosage of lanthanum carbonate, it was possible to maintain post-switch serum P concentrations at almost the same levels as before the switch. Furthermore, there were minor, yet significant improvements in acidosis (P<0.01). From these results, it was shown that bixalomer can be useful treatment alternative in dialysis patients for whom it is necessary to change the P binder due to insufficient management of serum P concentrations or development of acidosis.

Oral administration of Bifidobacterium longum in a gastro-resistant seamless capsule decreases serum phosphate levels in patients receiving haemodialysis.

Oral administration of Bifidobacterium longum in a gastro-resistant seamless capsule decreases serum phosphate levels in patients receiving haemodialysis.

Abdominal X-ray might be a useful tool for assessing medication adherence in patients receiving Lanthanum carbonate

Control of the serum phosphate (P) level is the most important and challenging in dialysis patients, because hyperphosphatemia is closely associated with higher cardiovascular morbidity and mortality. Lanthanum carbonate (LC), which is a novel non-calcium phosphate P binder, is effective in decreasing the serum P level and is well-tolerated with fewer adverse effects. However, LC has been reported that ingested LC fragments could be detectable in abdominal X-ray and computed tomography, because its density is between that of bone and metal. We performed an observational study to assess the relationship clinical effects of LC and abdominal X-ray findings in dialysis patients receiving LC. The enrolled 39 patients (female 7 (17.9%), age 59.6 yrs, dialysis vintage 11.2 yrs, diabetes 15 (38.5%)) were made abdominal X-ray examination at 4, 8, and 12 weeks after LC administration. Serum albumin, creatinine, and alkaline phosphatase levels did not change significantly during the 12-week treatment period. The P and the parathyroid hormone levels decreased after LC administration. Abdominal X-ray examination revealed digested LC tablets, in a variety of forms, through the intestinal tract in 37 patients (94.9%). The two patients without any digested LC fragment were still hyperphosphatemic after LC prescription, and they admitted not to have taken LC. Their serum P levels rapidly decreased after a series of medication counseling. In conclusion, this study suggested that abdominal X-ray might be useful tool for assessing medication adherence in patients receiving LC.

Conversion to lanthanum carbonate monotherapy effectively controls serum phosphorus with a reduced tablet burden: a multicenter open-label study

BackgroundLanthanum carbonate (FOSRENOL®) is an effective, well-tolerated phosphate binder. The ability of lanthanum to reduce serum phosphorus levels to ≤5.5 mg/dL in patients with end-stage renal disease (ESRD) was assessed in a clinical practice setting.MethodsA 16-week, phase IV study enrolled 2763 patients at 223 US sites to evaluate the efficacy of lanthanum carbonate in controlling serum phosphorus in patients with ESRD, and patient and physician satisfaction with, and preference for, lanthanum carbonate after conversion from other phosphate-binder medications. Patients received lanthanum carbonate prescriptions from physicians. These prescriptions were filled at local pharmacies rather than obtaining medication at the clinical trial site. Changes from serum phosphorus baseline values were analyzed using paired t tests. Patient and physician preferences for lanthanum carbonate versus previous medications were assessed using binomial proportion tests. Satisfaction was analyzed using the McNemar test. Daily dose, tablet burden, and laboratory values including albumin-adjusted serum calcium, calcium × phosphorus product, and parathyroid hormone levels were secondary endpoints.ResultsSerum phosphorus control (≤5.5 mg/dL) was effectively maintained in patients converting to lanthanum carbonate monotherapy; 41.6% of patients had controlled serum phosphate levels at 16 weeks. Patients and physicians expressed markedly higher satisfaction with lanthanum carbonate, and preferred lanthanum carbonate over previous medication. There were significant reductions in daily dose and daily tablet burden after conversion to lanthanum carbonate.ConclusionsSerum phosphorus levels were effectively maintained in patients converted from other phosphate-binder medications to lanthanum carbonate, with increased satisfaction and reduced tablet burden.Trial RegistrationClinicalTrials.gov: NCT0016012

Lanthanum carbonate reduces FGF23 in chronic kidney disease Stage 3 patients

In chronic kidney disease (CKD) patients, the ability to excrete a phosphate load is impaired. Compensatory increase in parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) promote phosphaturia. Serum FGF23 concentration is considered an early biomarker of excess phosphate load and high levels of FGF23 have been associated with increased mortality. In the present study, we have evaluated the changes in plasma FGF23 after treatment with the phosphate binder lanthanum carbonate in patients with CKD-3 and a normal serum phosphate concentration. Eighteen Caucasian CKD Stage 3a/3b patients with serum phosphate <4.5 mg/dL were recruited in a prospective longitudinal open-label study. Patients received a 4-week period of standardized phosphorus-restricted diet containing 0.8 g/Kg/day protein. Thereafter, the same diet was maintained and patients received lanthanum carbonate (750 mg with the three main meals) for 4 weeks. No significant changes were observed in serum phosphate, however, lanthanum carbonate significantly decreased urinary excretion of phosphate and fractional excretion of phosphate (P < 0.004). This was accompanied by a significant decrease in carboxyterminal FGF23 (median percent change from baseline -21.8% (interquartile range -4.5, -30%), P = 0.025). No changes were observed in PTH. In conclusion, lanthanum carbonate reduced phosphate load, as assessed by urinary phosphate excretion, and also reduced plasma FGF23 in CKD-3 patients. This occurs in the presence of unchanged normal serum phosphate levels.

Pharmacology of the Phosphate Binder, Lanthanum Carbonate

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.

Lanthanum Carbonate Reduces Phosphorus Burden in Patients with CKD Stages 3 and 4

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. 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. At the end of treatment, 25 (44.6%) versus nine (26.5%) patients had serum phosphorus < or =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. 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.

Lanthanum Carbonate Treatment of Hyperphosphatemia in End-Stage Renal Disease

Objective: To review the literature on the safety and efficacy of lanthanum carbonate for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). Data Sources: Primary literature was obtained through a PubMed search (1966–September 2005) using the key terms Fosrenol and lanthanum carbonate. The FDA review, manufacturer-provided data, and published abstracts on lanthanum carbonate were also reviewed and evaluated. Study Selection and Data Extraction: Human studies in which lanthanum carbonate was compared with placebo or active control for the treatment of hyperphosphatemia secondary to renal disease were included. Dose-titration studies were excluded. Data Synthesis: Phosphate-lowering agents and dietary phosphate restriction are currently the first-line therapies for initial treatment of hyperphosphatemia associated with ESRD. Lanthanum carbonate is a highly effective non–aluminum, non–calcium-containing phosphate binder. It is the only FDA-approved phosphate binder that is available as an unflavored chewable tablet that may be taken without water. Conclusions: Clinical studies demonstrate that lanthanum carbonate is more effective than placebo but as or less effective than standard therapies in lowering serum phosphate to target levels. When compared with calcium salts, lanthanum carbonate had a lower incidence of hypercalcemia and a lower risk of patients developing bone disease. However, in clinical trials, patients receiving lanthanum carbonate had greater discontinuation rates, some due to adverse events. The long-term safety data (&gt;5 y), including the potential for lanthanum accumulation in the bone with subsequent development of osteodystrophy, remain unknown.

Lanthanum carbonate (Fosrenol®) efficacy and tolerability in the treatment of hyperphosphatemic patients with end-stage renal disease

High serum phosphorus levels are a common problem in patients receiving long-term dialysis treatment. Lanthanum carbonate (Fosrenol) is a new non-aluminum, non-calcium phosphate binder developed for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). We report data from a recent trial, which, for the first time, assessed the efficacy and tolerability of lanthanum carbonate treatment, compared with placebo, in Chinese patients with ESRD. Following a one- to three-week washout phase and a four-week, open-label lanthanum carbonate dose-titration phase, male and female hemodialysis patients were randomized (1:1) to receive either lanthanum carbonate or placebo for four weeks. The primary efficacy parameter of the study was the control of serum phosphorus levels (< or =1.8 mmol/l [< or = 5.6 mg/dl]). Secondary endpoints included the profile of serum phosphorus during titration and parathyroid hormone, calcium, and calcium x phosphorus (Ca x P) product levels. The safety and tolerability of lanthanum carbonate were assessed by monitoring adverse events throughout the study. Mean serum phosphorus level at the end of washout was 2.5 +/- 0.5 mmol/l (7.7 +/- 1.5 mg/dl; n=73), and there was no evidence of a difference in levels between the treatment groups pre-randomization. At the end of the study, lanthanum carbonate-treated patients had significantly lower phosphorus levels (1.6 +/- 0.5 mmol/l [5.1 +/- 1.5 mg/dl]; n=30) than those receiving placebo (2.3 +/- 0.4 mmol/l [7.2 +/- 1.3 mg/dl]; n=31; p < 0.001). In addition, a significantly higher proportion of patients receiving lanthanum carbonate had controlled serum phosphorus levels (60%) compared with the placebo group (10%; p < 0.001). Ca x P product levels were also significantly lower in the lanthanum carbonate group at the end of randomized treatment (p < 0.001). Lanthanum carbonate was well tolerated; only one serious adverse event was reported, which was unrelated to treatment. Lanthanum carbonate was shown to be an effective and well-tolerated phosphate binder for the treatment of hyperphosphatemia in Chinese patients with ESRD. This finding supports the results of previous US and European studies, which have also shown that lanthanum carbonate treatment effectively controls serum phosphorus levels.

A long-term, open-label extension study on the safety of treatment with lanthanum carbonate, a new phosphate binder, in patients receiving hemodialysis

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 serum calcium, calcium × phosphorus product, and parathyroid hormone levels.Results: Lanthanum carbonate was well tolerated and was associated with few treatment-related adverse events. The most commonly reported adverse events were nausea (26.0%), peripheral edema (23.4%), and myalgia (20.8%). No treatment-related serious adverse events occurred. By Week 4, the mean serum phosphorus level had decreased by approximately 1 mg/dL to 5.7 ± 2.0 mg/dL (1.84 ± 0.7 mmol/L). At the end of the study, the mean pre-dialysis serum phosphorus level was 5.7 ± 1.4 mg/dL (1.84 ± 0.5 mmol/L); 53% of patients had controlled phosphorus levels. Calcium × phosphorus product decreased during Week 1 and remained within a clinically acceptable range thereafter. There were no clinically significant changes in serum calcium, or parathyroid hormone levels.Conclusion: Lanthanum carbonate is well tolerated and is effective for the long-term maintenance of serum phosphorus control in patients with end-stage renal disease.

Improving outcomes in hyperphosphataemia.

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.