Use Of Lanthanum Carbonate Research Articles

Effects of the combined use of lanthanum carbonate and activated carbon capping materials on phosphorus and dissolved organic matter in lake sediments

Lanthanum carbonate (LC) represents a novel material for the immobilization of internal phosphorus (P) in sediments. Activated carbon (AC) is a traditional adsorbent that has been employed in the remediation of sediments on a wide scale. The objective of this study is to examine the mechanisms and effects of the combined use of LC and AC capping materials on the immobilization of P and dissolved organic matter (DOM) in sediments, through a 90-day incubation experiment. The results of isotherm experiments showed that the adsorption mechanism of P on LC and AC was mainly chemisorption. The XPS analyses showed the adsorption mechanism of P on LC was mainly ligand exchange and inner-sphere complexation; while the adsorption mechanism of P on AC was mainly ligand exchange and electrostatic adsorption. The results demonstrated that the concentrations of soluble reactive phosphorus (SRP) and DOM in the 0 to −100 mm sediment layer were reduced by 69.79% and 33.93%, respectively, in comparison to the control group with the LC + AC group. Moreover, the HCl-P and Res-P (stable P) in the 0–5 cm sediment layer were increased by 50.07% and 21.04%, respectively, in the LC + AC group. This indicates that the combined application of LC and AC has the potential to reduce the risk of P release. Furthermore, the formation of Fe(III)/Mn(IV) oxyhydroxides by LC + AC treatment resulted in an increased adsorption of SRP and DOM. Moreover, the effect of LC + AC capping on microbial community was smaller than that of LC/AC capping alone. The findings of this study indicated that the combined use of LC and AC represents a novel approach to the effective treatment of internal P and DOM in eutrophic lake sediments.

Clinical Evaluation of the Safety, Efficacy and Tolerability of Lanthanum Carbonate in the Management of Hyperphosphatemia in Patients with End-Stage Renal Disease.

Patients with progressive chronic kidney disease (CKD) commonly develop mineral and bone abnormalities and extraskeletal calcifications with following increased cardiovascular risk. A key pathophysiological role is played by hyperphosphatemia. Since diet and dialysis are often insufficient to control serum phosphorus levels, many patients require treatment with phosphate binders. Among them is lanthanum carbonate, an aluminum-free non-calcium-based compound. The present review summarizes the most recent literature data concerning the safety, efficacy and tolerability of lanthanum carbonate in patients with end-stage renal disease and hyperphosphatemia. The drug is taken orally as chewable tablets or powder with only minimal gastrointestinal absorption and resulting reduced risk of tissue deposition and systemic drug interactions. The dissociation of the drug in the acid environment of the upper gastrointestinal tract induces the release of lanthanum ions, which bind to dietary phosphate forming insoluble complexes then excreted in the feces. Even though there is no clear evidence that lowering serum phosphorus levels can improve patient-centered outcomes, a mortality benefit with all phosphate binders, especially non-calcium containing ones, is not excluded. Lanthanum carbonate has been suggested to decrease all-cause mortality but not cardiovascular event rate compared to other phosphate binders. It induces a lower suppression of bone turnover than calcium carbonate and calcium acetate and may improve systolic function and cardiac dimension compared to calcium carbonate. Moreover, the use of lanthanum carbonate has been associated with better nutritional status compared to other phosphate binders, lower risk for hypercalcemia than calcium-containing binders, and amelioration of mild metabolic acidosis contrary to sevelamer hydrochloride. Main adverse effects include nausea, alkaline gastric reflux, gastric deposition of lanthanum, gastrointestinal obstruction, subileus, ileus, perforation, fecal impaction, and reduction of gastrointestinal absorption of some drugs including statins, angiotensin-converting enzyme inhibitors and some antibiotics such as fluoroquinolones or tetracyclines.

Gastropathy associated with lanthanum phosphate deposition that was endoscopically tracked for 3\u2009years. A case report

BackgroundWith the recent increased use of lanthanum carbonate, several cases of lanthanum phosphate deposition to gastric mucosa in dialysis patients have been reported. However, the endoscopic appearance of the early-stage lesion and the over-time alterations of endoscopic findings due to the progression of lanthanum phosphate deposition remain unclear.Case presentationAn 80-year-old man receiving dialysis and taking lanthanum carbonate as a phosphate binder over a 4-year period underwent upper gastrointestinal endoscopy four times beginning 1 year after initiation of treatment. The first endoscopic examination (after 1 year of exposure to lanthanum carbonate) revealed rough mucosa with a few areas of white granular mucosa. Over the 3 years of endoscopic follow-up, the white granular mucosa spread and multiple erosions appeared. Histopathological findings of biopsy specimens from an erosion showed extensive infiltration by histiocytes containing deposits. Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) revealed that the presence of the deposits containing phosphorus and lanthanum in the gastric mucosa.On the basis of these results, the patient was diagnosed with gastropathy associated with lanthanum phosphate deposition.ConclusionsOver a 3-year period, endoscopic findings associated with lanthanum deposition gradually changed and expanded from the early stage.

Can we IMPROVE cardiovascular outcomes through phosphate lowering in CKD? Rationale and protocol for the IMpact of Phosphate Reduction On Vascular End-points in Chronic Kidney Disease (IMPROVE-CKD) study

IntroductionPatients with chronic kidney disease (CKD) are at heightened cardiovascular risk, which has been associated with abnormalities of bone and mineral metabolism. A deeper understanding of these abnormalities should facilitate...

Lanthanum Carbonate - A New Phosphate Binding Drug in Advanced Renal Failure.

Lanthanum (La) is considered to be a non-essential element. La has been used for several decades in China to improve yield in plant production and has also been shown to have significant performance enhancing effects in feeding trials on animal husbandry. The estimated dietary intake of La in humans is below 150 µg, which is lower than 10% of the estimated limit of safe and acceptable daily intake. The present review is based on literature search in available databases. Upon ingestion of La as carbonate, the lanthanum ion (La3+) is released in the stomach and traps dietary phosphate as insoluble lanthanum phosphate complexes in the gut, thereby inhibiting phosphate absorption. Lanthanum carbonate as a drug to lower serum phosphate in endstage kidney failure was approved for human use by the US FDA in 2004 and by the EU in 2006. When used to treat patients with advanced renal insufficiency, lanthanum carbonate is administered orally at a dose of maximally 3000 mg per day. The uptake of lanthanum ions from the gut to the circulation is negligible. And few systemic side effects have been recorded upon the use of lanthanum carbonate as a phosphate binding drug, although gastrointestinal discomfort with pain, vomiting and diarrhea may occur. Lanthanum carbonate has the potential to chelate to drugs with anionic groups and therapeutic co-administration with lanthanum carbonate may reduce the bioavailibility of drugs like tetracyclines, quinolones and levothyroxine. The findings in this review confirm that lanthanum carbonate is a clinically useful phosphate binding drug with few side effects in advanced renal failure.

Improvement of MBD Parameters in Dialysis Patients by a Switch to, and Combined Use of Lanthanum Carbonate: Josai Dialysis Forum Collaborative Study

The effects of lanthanum carbonate on MBD parameters were investigated in 59 hemodialysis patients who were taking calcium carbonate. Lanthanum carbonate (initial dosage: 750 mg/day), as a replacement for or in combination with calcium carbonate and/or sevelamer hydrochloride, was administered for 12 months with increase/decrease of dosages. Lanthanum carbonate replaced calcium carbonate for 21 cases and was co-administered in 38 cases. It replaced sevelamer hydrochloride in 20 cases and was co-administered in 10 cases. Both the number of cases to which calcium carbonate was administered and their dosages decreased to about 70-80% 12 months after the initiation, and cases administered sevelamer decreased to about 30%. In the cases for which lanthanum carbonate was co-administered, the dosages of calcium carbonate and sevelamer slightly decreased. A significant decrease in serum calcium level was observed. In the serum phosphorus levels (P levels), significant decrease compared with the initial level was observed only at six and nine months. Intact parathyroid hormone (iPTH) level remained stable at around 230 pg/mL without significant change. The dosage of vitamin D and cinacalcet remained without significant change. The results of this trial suggest that, if dosages of vitamin D and cinacalcet are adequately controlled, a switch to lanthanum carbonate and its concomitant use are effective to control the Ca and P levels without changing iPTH levels.

Encephalopathy caused by lanthanum carbonate

Lanthanum carbonate is a nonaluminum, noncalcium phosphate-binding agent, which is widely used in patients with end-stage chronic kidney disease. Until now, no significant side-effects have been described for the clinical use of lanthanum carbonate, and there are no available clinical data regarding its tissue stores.Here we report the case of a 59-year-old patient who was admitted with confusional syndrome. The patient received 3750 mg of lanthanum carbonate daily. Examinations were carried out, and the etiology of the encephalopathy of the patient could not be singled out. The lanthanum carbonate levels in serum and cerebrospinal fluid were high, and the syndrome eased after the drug was removed. The results of our study confirm that, in our case, the lanthanum carbonate did cross the blood-brain barrier (BBB).Although lanthanum carbonate seems a safe drug with minimal absorption, this work reveals the problem derived from the increase of serum levels of lanthanum carbonate, and the possibility that it may cross the BBB. Further research is required on the possible pathologies that increase serum levels of lanthanum carbonate, as well as the risks and side-effects derived from its absorption.

Improved Patient Phosphorus Outcomes with the Use of Lanthanum Carbonate

 These findings should be confirmed in a prospective, randomized, controlled trial. CONCLUSIONS • The mean phosphorus levels decreased from baseline levels of 6.4 ± 1.8 mg/dL to 4.7 ± 1.0 mg/dL (p<0.001) after 2 months on lanthanum carbonate (Fig. 1A). PTH also decreased significantly (Fig. 1B). • After 2 months on lanthanum carbonate, the percent of patients meeting KDOQI guidelines increased from a baseline of 33% to 80% (Fig. 3A). • Comparing only patients who switched from a resinbased binder to lanthanum carbonate, serum phosphorus decreased (Fig. 2A) and a greater percent of patients were within KDOQI phosphorus guidelines (Fig. 3B) after 2 months on lanthanum carbonate. • Calcium and albumin did not change significantly for either comparison. • 33 patients (Table 1) who either switched to lanthanum carbonate from:

A confusional state associated with use of lanthanum carbonate in a dialysis patient: a case report

Sir, Muller and colleagues report a case of febrile confusion and ‘diverticular flare-up’ with abdominal pain and speculate an association with lanthanum carbonate (LC) because discontinuation of LC treatment and initiation of antibiotic therapy led to recovery [1]. They support their argument with the radiographic detection of lanthanum particles in the gastrointestinal tract, a reduction of plasma lanthanum levels following discontinuation of treatment and a selective review of the literature. However, there is no convincing argument for an association with LC treatment. The only available presentation of LC (FOSRENOL®, Shire Pharmaceuticals, Basingstoke, UK) is a chewable tablet containing no excipients to aid dispersal. Tablets should be taken with or immediately after meals and should be chewed completely; intact tablets should not be swallowed [2]. The size of the lanthanum particles evident in the radiograph is consistent with that of chewed LC, as has been seen in other published reports and not been associated with gastrointestinal obstruction [3,4]. As expected, and noted by the authors, the lanthanum particles ‘continued to migrate through the digestive tract’. In contrast, the case report by Kurtz (sic) et al. (Kongress der Gesellschaft fur Nephrologie, Tubingen, Germany, 2008) cited by Muller clearly showed the presence of un-chewed tablets. Speculation that deposition of lanthanum in the central nervous system (CNS) resulted in the confusional state draws on controversial evidence from in vivo studies [5,6]. Recent data from a study examining the potential for contamination of tissue samples in dietary studies of LC leads one to question the validity of this evidence [7]. In this study comparing dietary, oral gavage and intravenous administration, lanthanum was only detectable in brain tissue from rats administered LC in their diet. It appears that despite stringent efforts to limit contamination, lanthanum is still transferred to tissue samples during autopsy [7]. In another recent study, Bervoets et al. demonstrated no difference in the brain concentrations of lanthanum between healthy rats and those with chronic renal failure treated by oral gavage with LC for 20 weeks [8]. Levels remained around the lower limit of quantification for the assay. The results of these studies add to the weight of evidence in the literature that lanthanum does not cross the blood–brain barrier, even in the uraemic inflammatory and other disease states [8–10]. In the study by Feng et al., which suggests alteration of CNS function with lanthanum treatment, changes in biochemical parameters were not dose dependent and not predictive of effects in humans as discussed in the literature [6,11]. In addition, the authors do not consider the clinical data on the effects of LC on cognitive function [12]. Altmann et al. found no difference in the rate of cognitive decline in dialysis patients randomized to LC or standard phosphate-binder therapy (mainly calcium based) [12]. In this study, the median plasma lanthanum level of LC-treated patients stabilized at ∼0.3 (range 0.0–3.1) ng/mL. Therefore, the plasma lanthanum value of 2.13 μg/L noted by Muller et al. is neither ‘higher than normal’ compared with a population treated with LC for 2 years, nor is it associated with excessive cognitive decline. Extrapolation from in vivo tissue deposition data [8] based on human plasma lanthanum levels [13] is not scientifically sound and the conclusion that toxic levels of lanthanum can be reached in patients with renal failure is purely speculative, with no human or animal evidence provided. This patient was elderly and had diffuse cerebral atrophy on CT scan. Her presenting symptoms included dizziness with falling and confusion. Infection is commonly implicated with the etiology of several conditions that cause confusion in the elderly, and therapy of the underlying condition leads to recovery [14]. Benzodiazepine use is also commonly associated with confusion in the elderly. Either of these factors are plausible explanations for the confusion experienced by this patient. In summary, this patient with known diverticular disease presented with a febrile episode that responded to antibiotic treatment. The authors noted the expected radio-opaque appearance of lanthanum in the gastrointestinal tract and plasma lanthanum levels within the range observed in pivotal clinical trials. Neither finding has been convincingly linked to the patient's presentation; therefore, there are no grounds for revising the benefit–risk profile for LC. Conflict of interest statement. MS and RDP are employees of Shire Pharmaceuticals.

A confusional state associated with use of lanthanum carbonate in a dialysis patient: a case report

A 75-year-old woman was admitted with febrile confusion and abdominal pain. She was taking medications that included lanthanum carbonate. Examination, biology, a cerebral scan, and a review of her medications could not explain the confusion. The plain film of the abdomen revealed multiple diffuse calcium-like deposits throughout the digestive tract. The plasma levels of lanthanum were higher than normal. The confusion resolved after discontinuation of the lanthanum carbonate. This case raises the problem of the potential role played by lanthanum tablet residue in the genesis or aggravation of diverticular flare-up and the problem of the potential permeability of the blood-brain barrier with lanthanum use in case of its digestive accumulation, leading to increased serum concentrations.

Cognitive function in Stage 5 chronic kidney disease patients on hemodialysis: No adverse effects of lanthanum carbonate compared with standard phosphate-binder therapy

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.