Effect of lanthanum carbonate on serum calciprotein particles in patients with stage 3-4 CKD-results from a placebo-controlled randomized trial.

BACKGROUND: Calciprotein particles (CPP) are colloidal aggregates of calcium phosphate and the mineral-binding protein fetuin-A, and are potential mediators of cardiovascular disease in chronic kidney disease (CKD). Emerging evidence suggests non-calcium-containing phosphate binders may reduce serum CPP in patients with kidney failure who require dialysis; however, it is unclear whether similar interventions are effective in patients with earlier stages of CKD. METHODS: The IMpact of Phosphate Reduction On Vascular End-points in CKD (IMPROVE-CKD) was a multi-centre, placebo-controlled, randomized trial of lanthanum carbonate on cardiovascular markers in 278 participants with stage 3b/4 CKD. In this pre-specified exploratory analysis, primary (CPP-I) and secondary CPP (CPP-II) were measured in a sub-cohort of participants over 96 weeks. Treatment groups were compared using linear mixed-effects models and the relationship between serum CPP and pulse wave velocity (PWV) and abdominal aortic calcification (AAC) was examined. RESULTS: A total of 253 participants had CPP data for baseline and at least one follow-up timepoint and were included in this analysis. The mean age was 62.4 ± 12.6 years, 32.0% were female and the mean estimated glomerular filtration rate (eGFR) was 26.6 ± 8.3 mL/min/1.73 m2. Baseline median serum CPP-I was 14.9 × 104 particles/mL [interquartile range (IQR) 4.6-49.3] and median CPP-II was 3.3 × 103 particles/mL (IQR 1.4-5.4). There was no significant difference between treatment groups at 96 weeks in CPP-I [22.8% (95% confidence interval -39.2, 36.4), P = 0.65] or CPP-II [-18.3% (95% confidence interval -40.0, 11.2), P = 0.20] compared with a placebo. Serum CPP were not correlated with baseline PWV or AAC, or with the progression of either marker. CONCLUSIONS: Lanthanum carbonate was not associated with a reduction of CPP at 96 weeks when compared with a placebo in a CKD cohort.

Optimal Phosphate Control Related to Coronary Artery Calcification in Dialysis Patients.

BACKGROUND: In patients on maintenance dialysis, cardiovascular mortality risk is remarkably high, which can be partly explained by severe coronary artery calcification (CAC). Hyperphosphatemia has been reported to be associated with the severity of CAC. However, the optimal phosphate range in patients on dialysis remains unknown. This study was planned to compare the effects on CAC progression of two types of noncalcium-based phosphate binders and of two different phosphate target ranges. METHODS: We conducted a randomized, open-label, multicenter, interventional trial with a two by two factorial design. A total of 160 adults on dialysis were enrolled and randomized to the sucroferric oxyhydroxide or lanthanum carbonate group, with the aim of reducing serum phosphate to two target levels (3.5-4.5 mg/dl in the strict group and 5.0-6.0 mg/dl in the standard group). The primary end point was percentage change in CAC scores during the 12-month treatment. RESULTS: The full analysis set included 115 patients. We observed no significant difference in percentage change in CAC scores between the lanthanum carbonate group and the sucroferric oxyhydroxide group. On the other hand, percentage change in CAC scores in the strict group (median of 8.52; interquartile range, -1.0-23.9) was significantly lower than that in the standard group (median of 21.8; interquartile range, 10.0-36.1; P=0.006). This effect was pronounced in older (aged 65-74 years) versus younger (aged 20-64 years) participants (P value for interaction =0.003). We observed a similar finding for the absolute change in CAC scores. CONCLUSIONS: Further study with a larger sample size is needed, but strict phosphate control shows promise for delaying progression of CAC in patients undergoing maintenance hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Evaluate the New Phosphate Iron-Based Binder Sucroferric Oxyhydroxide in Dialysis Patients with the Goal of Advancing the Practice of EBM (EPISODE), jRCTs051180048.

Comparison of the effects of lanthanum carbonate and calcium carbonate on the progression of cardiac valvular calcification after initiation of hemodialysis.

BACKGROUND: Although mineral metabolism disorder influences cardiac valvular calcification (CVC), few previous studies have examined the effects of non-calcium-containing and calcium-containing phosphate binders on CVC in maintenance hemodialysis patients. The aim of the present study was to compare the effects of lanthanum carbonate (LC) with calcium carbonate (CC) on the progression of CVC in patients who initiated maintenance hemodialysis and to investigate clinical factors related to CVC. METHODS: The current study included 50 subjects (mean age 65 years, 72% males) from our previous randomized controlled trial (LC group, N = 24; CC group, N = 26). CVC was evaluated as CVC score (CVCS) using echocardiography at baseline and 18 months after initiation of hemodialysis. We compared CVCS and the changes between the two groups. We also analyzed the associations between CVCS and any other clinical factors including arterial plaque score (PS) and serum phosphorus levels. RESULTS: Baseline characteristics of study participants including CVCS were almost comparable between the two groups. At 18 months, there were no significant differences in mineral metabolic markers or CVCS between the two groups, and CVCS were significantly correlated with PS (r = 0.39, p < 0.01). Furthermore, changes in CVCS were significantly correlated with average phosphorus levels (r = 0.36, p < 0.05), which were significantly higher in high serum phosphorus and high PS group compared to low serum phosphorus and low PS group (p < 0.05). CONCLUSIONS: In the present study, there were no significant differences between LC and CC with regard to progression of CVC. However, serum phosphorus levels and arterial plaque seem to be important for the progression and formation of CVC in hemodialysis patients.

Distribution of lanthanum carbonate in the gastric mucosa confirmed by electron microscopy with a magnified endoscopy: a case report and literature review.

We describe the case of a 70-year-old man with diabetic nephropathy undergoing hemodialysis. Four years following hemodialysis, he started taking lanthanum carbonate 1500 mg/day and lansoprazole 30 mg/day. Nine years following hemodialysis, he underwent screening esophagogastroduodenoscopy, which demonstrated the presence of the whitish cobblestone-like mucosa in the gastric corpus and multiple reddish depressed lesions with annular whitish mucosa in the antrum. With magnified narrow-band imaging endoscopy, a yellowish-white substance was observed in the villous structure, and subepithelial vessels were observed on the yellowish-white substance. Biopsies were taken from the whitish cobblestone-like mucosa of the upper corpus, a reddish depressed part of the antrum. Histologically, aggregates of cells containing amphophilic fine granular material were found in the mucosal interstitium. These cells stained positive for CD68 and were identified as histiocytes. Since he had been taking lanthanum carbonate for 5 years, we considered the possibility of histiocyte-mediated phagocytosis of lanthanum. Digital mapping via scanning electron microscopy with energy-dispersive X-ray spectrometry showed the presence of lanthanum and phosphorus in the interstitium and cytoplasm of histiocytes. The white, rough mucosa in the gastric body appeared 6 months following the commencement of lanthanum administration and still exists 3 years and 5 months after discontinuation of lanthanum.

[Deposits of lanthanum in the gastric mucosa of a patient with chronic kidney disease]. / Depósito de lantano en la mucosa gástrica de paciente con enfermedad renal crónica.

Lanthanum carbonate is a non-calcium phosphorus chelator used in the treatment of hyperphosphatemia associated with chronic renal disease. Deposits of lanthanum in the gastrointestinal wall have been recently described but its clinical significance is uncertain. We present a case of a 62-year-old male with chronic renal disease treated with lanthanum carbonate for 3 years, with deposits in his gastric mucosa, found on biopsy for dyspepsia. The deposits were acellular and of irregular shape, surrounded by macrophages and foreign body giant cells. The presence of lanthanum in the deposits was confirmed by X-ray spectroscopy. Diagnosis is reached with knowledge of its microscopic appearance and a thorough clinical history.

Lanthanum carbonate, a phosphate binder, inhibits calcification of implanted aortic allografts in a rat model.

OBJECTIVES: Calcification is one of the major postoperative problems after aortic allograft implantation. We hypothesized that phosphate binders, lanthanum carbonate and calcium carbonate inhibit calcification of implanted aortic allografts and verified this hypothesis using a rat model. METHODS: Aortas were harvested from 4-week-old Brown Norway rats and implanted into the subdermal space of 4-week-old Lewis rats. Twenty-seven recipient Lewis rats were divided into Group N, Group L, and Group C (9 rats per group), which were fed a normal diet, a normal diet containing 3% lanthanum carbonate, and a normal diet containing 3% calcium carbonate, respectively. Implanted aortic allografts were explanted 2 weeks later. Calcification of aortic allografts was evaluated using von Kossa staining and calcium content assay. Calcification score was defined in von Kossa staining as 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Serum calcium and phosphorus levels at euthanasia were measured. RESULTS: Calcification scores were 2.6, 1.2, and 0.8, and calcium content was 48.9, 15.8, and 8.9 mg/dry·g, in Groups N, L, and C, respectively. Calcification was significantly reduced in Groups L and C. Serum calcium level was 11.5, 12.2, and 13.5 mg/dl, and serum phosphorus level was 15.4, 12.5, and 11.7 mg/dl, in Groups N, L, and C, respectively. Serum calcium level in Group C was significantly higher than in the other two groups. CONCLUSIONS: Lanthanum carbonate and calcium carbonate significantly reduced calcification of implanted aortic allografts in young rats. Although calcium carbonate induced hypercalcemia, lanthanum carbonate has significant potential to inhibit calcification of implanted aortic allografts.

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.

Successful Treatment of Tumoral Calcinosis by Lanthanum Carbonate.

Tumoral calcinosis (TC) is a rare benign but aggressive disorder with variable response rates and high recurrence rates despite medical or surgical treatments. We herein report a case of a 28-year-old woman with underlying systemic lupus erythematosus (SLE) who developed diffuse tumoral calcinosis that was successfully treated by lanthanum carbonate. The formation of tumoral calcinosis depends on the supersaturation of calcium and phosphate. Lanthanum carbonate not only has an excellent phosphate-lowering ability but also low gastro-intestinal calcium absorption. It can be considered an effective alternative treatment for tumoral calcinosis if surgical treatment is not feasible.

135La as an Auger-electron emitter for targeted internal radiotherapy.

135La has favorable nuclear and chemical properties for Auger-based targeted internal radiotherapy. Here we present detailed investigations of the production, emissions, and dosimetry related to 135La therapy. 135La was produced by 16.5 MeV proton irradiation of metallic natBa on a medical cyclotron, and was isolated and purified by trap-and-release on weak cation-exchange resin. The average production rate was 407 ± 19 MBq µA-1 (saturation activity), and the radionuclidic purity was 98% at 20 h post irradiation. Chemical separation recovered > 98 % of the 135La with an effective molar activity of 70 ± 20 GBq µmol-1. To better assess cellular and organ dosimetry of this nuclide, we have calculated the x-ray and Auger emission spectra using a Monte Carlo model accounting for effects of multiple vacancies during the Auger cascade. The generated Auger spectrum was used to calculate cellular S-factors. 135La was produced with high specific activity, reactivity, radionuclidic purity, and yield. The emission spectrum and the dosimetry are favorable for internal radionuclide therapy.

Effect of lanthanum carbonate on coronary artery calcification and bone mineral density in maintenance hemodialysis patients with diabetes complicated with adynamic bone disease: A prospective pilot study.

BACKGROUND: The incidence of adynamic bone disease (ABD) is increasing. Coronary artery calcification (CAC) may be severe in patients with ABD on maintenance hemodialysis (MHD). The aim of this study was to evaluate the effect of lanthanum carbonate (LC) on CAC and bone mineral density (BMD) in MHD patients with diabetes complicated with ABD. METHODS: A total of 92 MHD cases were divided into the calcium carbonate (CC) and LC groups. Primary outcome measure was the changes in the degree of CAC score (CACS) and BMD in forearm from baseline to 12 months. Secondary outcomes included changes in serum markers of CKD-MBD and side-effects. RESULTS: After 12 months, serum levels of calcium, phosphate, FGF23, and MGP were decreased significantly, while iPTH, b-ALP, PINP and ß-CTX, and CACS and BMD were increased in LC group compared with those at baseline (P < .05). After 12 months treatment, serum levels of calcium, phosphate, FGF23, and CACS were lowered, while MGP, b-ALP, PINP, ß-CTX, BMD, and iPTH were higher in LC group than in CC group. Pearson correlation analyses revealed that BMD in forearm was positively correlated with iPTH and MGP, while negatively with CACS. CACS was positively correlated with serum calcium, phosphate and FGF23, while negatively with serum MGP. Multivariate linear regression revealed changes of BMD in forearm and femoral neck and changes of serum FGF23 were independent influential factors for changes of CACS (P < .05). CONCLUSIONS: In MHD patients with diabetes complicated with ABD, lanthanum carbonate could delay CAC progress, and improve bone transport and bone density.

Gastric mucosal status susceptible to lanthanum deposition in patients treated with dialysis and lanthanum carbonate.

Lanthanum carbonate is a popular chemical which is administered for patients with end-stage kidney disease to reduce the absorption of phosphate, and lanthanum deposition in the gastroduodenal mucosa has recently been reported. The aim of this study was to assess whether any histologic changes of the gastric mucosa are related to the deposition of lanthanum. Twenty-four patients who revealed the histology of lanthanum deposition on gastroduodenal biopsy between 2011 and 2014 were included in the study, and their clinical records and gastroduodenal biopsies obtained from 2011 to 2015 were reviewed, adding the review of gastroduodenal biopsies before 2011 if possible. Analysis of the deposited materials by scanning electron microscopy-energy dispersive x-ray spectroscopy was performed for a representative gastric biopsy. All patients were diagnosed as having renal insufficiency due to chronic kidney disease and treated with dialysis for more than 5 years, with confirmation of lanthanum carbonate use for 22 patients. Of 121 gastric biopsies and 10 duodenal ones between 2011 and 2015, 86 gastric biopsies (71.1%) and 3 duodenal biopsies (30%), respectively, revealed histology consistent with lanthanum deposition, which was confirmed by scanning electron microscopy-energy dispersive x-ray spectroscopy analysis for a representative case. The deposition tended to occur in the gastric mucosa with regenerative change, intestinal metaplasia, or foveolar hyperplasia (P<.05). Such mucosal changes were observed in about half of the gastric biopsy samples obtained prior to 2010, in which no lanthanum deposition was identified irrespective of the gastric mucosal status. Although direct association between lanthanum deposition and clinical symptoms is not clear, the evaluation of the gastric mucosal status (prior to administration) seems to be important to predict lanthanum deposition when lanthanum carbonate is administered for patients with chronic kidney disease treated with dialysis.

The efficacy and safety of sevelamer and lanthanum versus calcium-containing and iron-based binders in treating hyperphosphatemia in patients with chronic kidney disease: a systematic review and meta-analysis.

Background: It remains unclear which phosphate binders should be preferred for hyperphosphatemia management in chronic kidney disease (CKD). Methods: We performed a systematic review and meta-analysis of randomized trials comparing sevelamer or lanthanum with other phosphate binders in CKD. Results: Fifty-one trials (8829 patients) were reviewed. Compared with calcium-based binders, all-cause mortality was nonsignificantly lower with sevelamer {risk ratio [RR] 0.62 [95% confidence interval (CI) 0.35-1.08]} and lanthanum [RR 0.73 (95% CI 0.18-3.00)], but risk of bias was concerning. Compared with calcium-based binders, sevelamer reduced the risk of hypercalcemia [RR 0.27 (95% CI 0.17-0.42)], as did lanthanum [RR 0.12 (95% CI 0.05-0.32)]. Sevelamer reduced hospitalizations [RR 0.50 (95% CI 0.31-0.81)], but not lanthanum [RR 0.80 (95% CI 0.34-1.93)]. The presence/absence of other clinically relevant outcomes was infrequently reported. Compared with calcium-based binders, sevelamer reduced serum calcium, low-density lipoprotein and coronary artery calcification, but increased intact parathyroid hormone. The clinical relevance of these changes is unknown since corresponding clinical outcomes were not reported. Lanthanum had less favorable impact on biochemical parameters. Sevelamer hydrochloride and sevelamer carbonate were similar in three studies. Sevelamer was similar to lanthanum (three studies) and iron-based binders (three studies). Conclusion: Sevelamer was associated with a nonsignificant reduction in mortality and significantly lower hospitalization rates and hypercalcemia compared with calcium-based binders. However, differences in important outcomes, such as cardiac events, fractures, calciphylaxis, hyperchloremic acidosis and health-related quality of life remain understudied. Lanthanum and iron-based binders did not show superiority for any clinically relevant outcomes. Future studies that fail to measure clinically important outcomes (the reason why phosphate binders are prescribed in the first place) will be wasteful.

Lanthanum phosphate deposition in the gastric mucosa of patients with chronic renal failure.

A 77-year-old Japanese man underwent endoscopic submucosal dissection twice over a 5-year period for the treatment of two separate early gastric cancers. He had been taking lanthanum carbonate, an orally administered phosphate binder, for 3 years. Esophagogastroduodenoscopy revealed reddish mucosa in the greater curvature and anterior wall of the gastric angle, while granular, white deposits were also observed in some areas of this reddish mucosa. Additionally, biopsy specimens from the gastric mucosa revealed the deposition of fine, amorphous, eosinophilic material, which appeared bright on scanning electron microscopy. Energy dispersive X-ray spectroscopy revealed the presence of lanthanum and phosphate in these bright areas, and elemental mapping confirmed that their distribution was identical to that seen in the bright areas. Based on these findings, the diagnosis of lanthanum phosphate deposition in the gastric mucosa was determined.

Novel iron-containing phosphate binders for treatment of hyperphosphatemia.

INTRODUCTION: Hyperphosphatemia is a frequent complication of chronic kidney disease and is associated with increased mortality. Despite side effects, risk of accumulation and high costs, phosphate binders (PBs) have become the crucial cornerstone of therapy. The iron-containing PB sucroferric oxyhydroxide (SO) and ferric citrate hydrate (FCH) have entered the market and other candidates are prior market entry. AREAS COVERED: A literature search was performed using MEDLINE and EMBASE databases to identify references on iron-containing PB with particular regard to efficacy, safety and potential benefits. Additional hand searches were conducted along with a full-text review of any citation that appeared relevant. EXPERT OPINION: On the highly competitive market, where the 'ideal' PB is still unknown, novel substances that offer clear benefits over available drugs are desired. Although SO and FCH showed similar efficacy and safety compared to sevelamer, head-to-head studies with lanthanum carbonate are absent. Clinical 1-year data in a limited patient cohort suggested improved adherence for SO and a large randomized controlled trial showed significant reduction in hospitalizations and costs for FCH. Additional large randomized controlled trials have now to prove these possible advantages. Cost-effectiveness in comparison to other PB and the exclusion of significant harms under long-term treatment will determine the future use of both drugs.

[Iron, aluminum, and lanthanum-based drugs for treatment of hyperphosphatemia].

The control of the serum phosphorus (P) level in chronic kidney disease patients is important because elevated serum P levels are associated with progression of vascular calcification and increased mortality in these patients. In 2014, a novel phosphate binder, ferric citrate hydrate (Riona(®)), became available for the treatment of hyperphosphatemia in Japan, the first country to approve this medication. Ferric citrate hydrate, which relies upon the potent phosphate-binding capacity of ferric iron, inhibits P absorption by forming complexes between ferric iron and dietary phosphate in the gut. The active pharmaceutical ingredient in ferric citrate hydrate provides a larger specific surface area and higher water solubility; therefore, it is expected to have greater efficacy in terms of its phosphate-binding capacity. In clinical trials, ferric citrate hydrate significantly reduced the serum phosphate level and effectively maintained serum P concentrations throughout the duration of the trials. Moreover, in one clinical trial, ferric citrate hydrate significantly decreased levels of fibroblast growth factor-23 (FGF-23) in nondialysis patients. FGF-23 is an endocrine hormone that increases urinary phosphate excretion to maintain serum P at the proper level. A portion of the iron from ferric citrate hydrate is absorbed and transported throughout the body as transferrin-bound iron, where it is used for the synthesis of hemoglobin, enzymes, and others. Although safer and more effective phosphate binders are expected in the future, ferric citrate hydrate will become a new approach for the treatment of hyperphosphatemia.

Extensive lanthanum deposition in the gastric mucosa: the first histopathological report.

Lanthanum carbonate is one of the new phosphate binders used for the treatment of hyperphosphatemia in patients with chronic kidney disease. It is poorly absorbed from the gastrointestinal tract, forms insoluble complexes within the lumen, and prevents the absorption of dietary phosphate. A 63-year-old female with a 7-year history of peritoneal dialysis, who was treated with lanthanum carbonate for four years, underwent endoscopic submucosal dissection for intramucosal gastric cancer. Resected specimens showed massive accumulation of macrophages containing fine, granular, brown material in the lamina propria. This was confirmed as lanthanum deposition by scanning electron microscopy with energy dispersive x-ray spectroscopy. Although lanthanum may be poorly absorbed, increased tissue accumulation of lanthanum, particularly in the liver and bone, has been reported in animals with chronic kidney disease. This report indicates enhanced gastrointestinal absorption of lanthanum in some patients or conditions, although its clinical significance awaits further studies.

CKD-induced wingless/integration1 inhibitors and phosphorus cause the CKD-mineral and bone disorder.

In chronic kidney disease, vascular calcification, renal osteodystrophy, and phosphate contribute substantially to cardiovascular risk and are components of CKD-mineral and bone disorder (CKD-MBD). The cause of this syndrome is unknown. Additionally, no therapy addresses cardiovascular risk in CKD. In its inception, CKD-MBD is characterized by osteodystrophy, vascular calcification, and stimulation of osteocyte secretion. We tested the hypothesis that increased production of circulating factors by diseased kidneys causes the CKD-MBD in diabetic mice subjected to renal injury to induce stage 2 CKD (CKD-2 mice). Compared with non-CKD diabetic controls, CKD-2 mice showed increased renal production of Wnt inhibitor family members and higher levels of circulating Dickkopf-1 (Dkk1), sclerostin, and secreted klotho. Neutralization of Dkk1 in CKD-2 mice by administration of a monoclonal antibody after renal injury stimulated bone formation rates, corrected the osteodystrophy, and prevented CKD-stimulated vascular calcification. Mechanistically, neutralization of Dkk1 suppressed aortic expression of the osteoblastic transcription factor Runx2, increased expression of vascular smooth muscle protein 22-α, and restored aortic expression of klotho. Neutralization of Dkk1 did not affect the elevated plasma levels of osteocytic fibroblast growth factor 23 but decreased the elevated levels of sclerostin. Phosphate binder therapy restored plasma fibroblast growth factor 23 levels but had no effect on vascular calcification or osteodystrophy. The combination of the Dkk1 antibody and phosphate binder therapy completely treated the CKD-MBD. These results show that circulating Wnt inhibitors are involved in the pathogenesis of CKD-MBD and that the combination of Dkk1 neutralization and phosphate binding may have therapeutic potential for this disorder.

Evaluation of aortic calcification with lanthanum carbonate vs. calcium-based phosphate binders in maintenance hemodialysis patients with type 2 diabetes mellitus: an open-label randomized controlled trial.

Vascular calcification (VC) contributes to cardiovascular disease in hemodialysis (HD) patients, especially with diabetes mellitus (DM) complications. No randomized studies have been published regarding the effect of lanthanum carbonate (LC) on VC progression in DM patients. The aim of this study was to evaluate the effects of lanthanum carbonate on the progression of VC in HD patients with type 2 DM. We conducted a randomized controlled trial comparing LC with calcium carbonate (CC) in 43 HD patients at a single dialysis center. Estimations of aortic calcification index (ACI) by abdominal computed tomography were performed twice for each patient (at baseline and 12 months). Forty-one patients completed the study (19 LC, 22 CC). When ACI at baseline was ≦0.48 (median of baseline ACI), median change in ACI (Δ%ACI) was 20.44 (11.50-36.80%) in the LC group, and 40.00 (33.30-92.60%) in the CC group (P = 0.026). On the other hand, when ACI at baseline was >0.48, the median change in ACI (Δ%ACI) was 6.42 (3.13-24.40%) in the LC group, and 8.08 (5.68-12.20%) in the CC group (P = 1.000). Serum markers of chronic kidney disease-mineral and bone disorder (CKD-MBD), HbA1c, dose of vitamin D analogues, and side-effects of medications did not change in either group throughout the study except int-PTH increased in the LC group. This study indicated that administration of LC inhibited the progression of VC in patients receiving HD for type 2 DM, only in cases of slight VC compared with CC.

High phosphate feeding induced arterial medial calcification in uremic rats: roles of Lanthanum carbonate on protecting vasculature.

AIMS: High cardiovascular mortality in patients with end-stage renal disease is closely associated with arterial medial calcification (AMC) caused by hyperphosphatemia, the mechanism of which associated hormones (FGF-23, klotho) and osteochondrogenic events is unclear. We examined the effect of Lanthanum carbonate on AMC via regulating the abnormalities in phosphorus metabolism of uremic rats. MAIN METHODS: 45 healthy SD rats were randomly divided into 3 groups: Normal group (n=15), CRF group (n=15), CRF diet supplemented with 2% La (n=15). AMC in great arteries were evaluated by VonKossa. Osteochondrogenic specific genes were analyzed by Immunohistochemistry and qRT-PCR. Serum FGF-23 and klotho levels were detected by ELISA kit. KEY FINDINGS: Serum phosphate was markedly increased in CRF group (6.94 ± 0.97 mmol/L) and 2%La group (5.12 ± 0.84 mmol/L) at week 4, while the latter became hypophosphatemic (2.92 ± 0.73 mmol/L vs CRF group, p<0.01) at week 10. Inhibitory effect of 2%La on development of AMC was reflected by downregulated Runx2, Osterix, BSP, Osteocalcin and collagenII and a reduction of FGF-23 at week 4(vs CRF group, p<0.01) but not week 10. SIGNIFICANCE: Beneficial effects of Lanthanum carbonate on progression of AMC in CRF could be mainly due to the decreased phosphate retention and FGF-23 in early stage and likewise a reduction of bone-associated proteins via osteochondrogenic pathway. Lanthanum carbonate has no effect on soluble klotho and serum FGF-23 in late stage of CRF.