Dose Of Lanthanum Carbonate Research Articles

Investigation of the clinical significance and pathological features of lanthanum deposition in the gastric mucosa

BackgroundThere are often specific endoscopic findings caused by deposition of lanthanum (La) in the gastric mucosa of patients taking lanthanum carbonate (LaC), a novel phosphate binder for patients on hemodialysis. We conducted a retrospective study to investigate the clinical significance of La deposition in the gastric mucosa, and the association between endoscopic features and histologic findings in the same population.MethodsWe compared background factors in patients taking LaC with and without La deposition in their gastroscopic biopsy specimen. We also investigated the relationship between gastric endoscopic biopsy specimens with La deposition and the concurrent endoscopic images.ResultsThere was a significant difference in the total dose of LaC between the La-positive and La-negative groups (990 g [180–3150 g] vs. 480 g [225–1328 g]; p = 0.013). In 27 biopsy specimens with specific whitish mucosa, 10 showed mild histiocytic infiltration and 17 showed severe infiltration. In contrast, among 24 specimens with non-whitish mucosa, 5 showed no histiocytic infiltration, 10 showed mild infiltration, and 9 showed severe infiltration. There was a significant relationship between endoscopic features and the degree of histiocytic infiltration (p = 0.026).ConclusionsWe demonstrated that La deposition in the gastric mucosa depended on the total dose of LaC and was not affected by background factors. The specific endoscopic features of La deposition are associated with the infiltration of histiocytes, which represents the body’s normal response to foreign bodies.Trial registry The protocol was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN000038929, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000044393).

A comparison of the long-term effects of lanthanum carbonate and calcium carbonate on the course of chronic renal failure in rats with adriamycin-induced nephropathy.

Lanthanum carbonate (LA) is an effective phosphate binder. Previous study showed the phosphate-binding potency of LA was twice that of calcium carbonate (CA). No study in which LA and CA were given at an equivalent phosphate-binding potency to rats or humans with chronic renal failure for a long period has been reported to date. The objective of this study was to compare the phosphate level in serum and urine and suppression of renal deterioration during long-term LA and CA treatment when they were given at an equivalent phosphate-binding potency in rats with adriamycin (ADR)-induced nephropathy. Rats were divided into three groups: an untreated group (ADR group), a CA-treated (ADR-CA) group and a LA-treated (ADR-LA) group. The daily oral dose of LA was 1.0 g/kg/day and CA was 2.0 g/kg/day for 24 weeks. The serum phosphate was lower in the ADR-CA or ADR-LA group than in the ADR group and significantly lower in the ADR-CA group than in the ADR group at each point, but there were no significant differences between the ADR and ADR-LA groups. The serum phosphate was also lower in the ADR-CA group than in the ADR-LA group, and there was significant difference at week 8. The urinary phosphate was significantly lower in the ADR-CA group than in the ADR or ADR-LA group at each point. The urinary phosphate was also lower in the ADR-LA group than in the ADR group at each point, and significant difference at week 8. There were no significant differences in the serum creatinine or blood urea nitrogen among the three groups. In conclusion, this study indicated the phosphate-binding potency of LA isn’t twice as strong as CA, and neither LA nor CA suppressed the progression of chronic renal failure in the serum creatinine and blood urea nitrogen, compared to the untreated group.

Pilot Study of the Effect of Lanthanum Carbonate (Fosrenol®) In Patients with Calciphylaxis: A Wisconsin Network for Health Research (WiNHR) Study.

BackgroundCurrently there is a lack of effective treatment options for patients with calciphylaxis. There is anecdotal evidence that non-calcium based phosphorus binders may offer some benefit. The aim of this pilot study is to determine if lanthanum carbonate is effective in inducing remission of calciphylaxis lesions and demonstrate an improved DLQI (Dermatology Life Quality Index).MethodsThis is a multi-site exploratory pilot study conducted through the Wisconsin Network for Health Research (WiNHR), a collaboration of health services researchers across the state of Wisconsin. Dialysis patients were recruited from in-center dialysis units, clinics and hospital admissions over a period of 24-months.ResultsDue to the low inclusion rate, the trial was terminated after which 4 patients were prospectively analyzed. Dose of lanthanum carbonate was escalated to 3750 mg divided into 3 meals and titrated according to level of serum phosphorus. Gastrointestinal symptoms were the most common adverse effect. All 4 patients achieved complete remission by definition of skin re-epithelialization. Secondary outcome measurements showed a significant improvement in serum albumin (B coeff 0.17, 95% CI 0.002-0.031; p=0.023) and a significant improvement in overall DLQI score (B coeff -0.46, 95% CI -0.85- -0.08; p=0.019).ConclusionsLanthanum carbonate appears to be efficacious as an adjunctive therapy to improve calciphylaxis lesions and symptom burden. More prospective clinical trials are warranted to determine the feasibility of this novel treatment strategy.

Measurement of serum lanthanum in patients treated with lanthanum carbonate by inductively coupled plasma-mass spectrometry

Lanthanum carbonate is used as a phosphate binder in patients with stage V chronic kidney disease (CKD). While well tolerated in clinical trials, with no toxicity reported as regards bone and liver metabolism, and cognitive function, concerns remain over possible toxicity. Published methods for the measurement of lanthanum ion in biological samples include aggressive and complicated sample preparation steps that are unsuitable for routine use. A simple method has been developed and validated for the measurement of serum lanthanum. A ThermoFisher Scientific XSERIES-II inductively coupled plasma-mass spectrometer was used to monitor ¹³⁹La. Validation was undertaken using internal quality control solutions containing lanthanum ion (0.20, 0.70 and 4.00 μg/L). Lanthanum was measured in patients (number = 20) with CKD prescribed lanthanum carbonate (500-1500 mg/d) and patients undergoing haemodialysis not prescribed lanthanum carbonate (number = 20). Accuracy and imprecision were >95% and <5%, respectively. Calibration was linear (range 0.1-5 μg/L, R² = 0.99). The lower limit of quantification (LLoQ) was 0.1 μg/L lanthanum ion. In patients with CKD not prescribed lanthanum carbonate, serum lanthanum was below the LLoQ. Out of 20 CKD patients prescribed lanthanum carbonate, serum lanthanum was measurable in only 12 (range 0.11-0.60 μg/L lanthanum ion). There was no apparent relationship between dose and serum lanthanum in these patients. A lack of relationship between the dose of lanthanum carbonate and the serum lanthanum concentration may have been due to poor adherence to the treatment regimen. However the concentrations measured were close to the LLoQ.

Utilization of bone histomorphometry in renal osteodystrophy: demonstration of a new approach using data from a prospective study of lanthanum carbonate

The aim of this study was to develop a novel approach to the analysis of bone histomorphometric data and outcomes presentation that would simplify the characterization of renal osteodystrophy and facilitate clinical decision-making. Data were derived from a randomized trial of dialysis patients treated for one year with a dose of lanthanum carbonate or calcium carbonate (up to 3750 mg/day and 9000 mg/day, respectively). Histomorphometric analyses of baseline and end-of-study bicortical transiliac bone biopsies were performed. Activation frequency, bone formation rate/bone surface, osteoclast surface/ bone surface, osteoblast surface/bone surface, mineralization lag time, and osteoid thickness were determined to provide a measure of overall bone cell activity (bone formation, bone resorption, bone turnover) and risk of developing osteopenia (bone balance). A novel approach of qualitatively grouping these numerical data as "improved", "unchanged", or "worsened" based on deviation from normal was used to facilitate interpretation of clinical relevance. Using our method, lanthanum carbonate was shown to improve histomorphometric parameters measured. These improvements were superior to those produced by calcium carbonate. These data add valuable clinical relevance to the previously published qualitative data from the same cohort [D'Haese et al. 2003]. Lanthanum carbonate moderated extreme forms of renal osteodystrophy, whereas calcium carbonate treatment increased the incidence of adynamic and predominant hyperparathyroid bone disease. This study provides an approach to the prospective evaluation of bone disease progression with therapy, and its application supports the safety and greater efficacy of one-year lanthanum carbonate versus calcium carbonate therapy as a means to normalize bone turnover in dialysis patients.

Assessment of effects of lanthanum carbonate with and without phosphate supplementation on bone mineralization in uremic rats

Previous studies have indicated that impaired bone mineralization in 5/6 th nephrectomized rats given high doses of lanthanum carbonate is due to phosphorus depletion caused by excessive binding to, and reduced absorption of, dietary phosphate. This study aimed to test this hypothesis by: 1) directly comparing the effects of a supratherapeutic dose of lanthanum carbonate or dietary phosphorus restriction on bone mineralization in a rodent model of chronic renal failure (CRF); and 2) investigating whether phosphorus supplementation would prevent the bone mineralization defect associated with lanthanum carbonate treatment. Male Sprague-Dawley rats were subjected to sham surgery or a two-step 5/6th nephrectomy to induce CRF and randomized across five treatment groups: sham, CRF, CRF + dietary phosphorus deficiency, CRF + lanthanum carbonate (1000 mg/kg/ day), and CRF + lanthanum carbonate + parenteral phosphorus repletion. Rats with 5/6th nephrectomy had elevated serum creatinine, blood urea concentration, and urine volume and protein, consistent with impaired renal function, and increased urinary phosphorus and serum parathyroid hormone, consistent with hyperparathyroidism. Lanthanum carbonate and dietary phosphate insufficiency induced parallel changes in serum and urine markers of phosphate homeostasis and increased osteoid formation. These changes induced by lanthanum carbonate were normalized by systemic phosphate supplementation. These findings provide further support for the concept that supratherapeutic doses of lanthanum carbonate induce effects on bone mineralization in uremic rats via an indirect pharmacological mechanism (phosphate depletion) and not via direct bone toxicity.

Effects of Efficient Phosphate Binding on Bone in Chronic Renal Failure Rats

Background. We recently reported that administration of high doses of lanthanum carbonate (1000 mg/kg/day) to chronic renal failure (CRF) rats can result in a mineralization defect. Our results suggested, however, that the impaired mineralization was not due to a direct toxic action of lanthanum on the bone, but rather was an indirect consequence of a phosphate depletion resulting from the compound's high phosphate-binding capacity. To further substantiate these results, in the present study, the effects of lanthanum carbonate on bone were compared to the effects of sevelamer, a nonabsorbed, non-metal-containing polymeric phosphate-binding agent. Methods. Male Wistar rats underwent a 5/6th nephrectomy to induce chronic renal failure, after which they were treated with either sevelamer (500 or 1000 mg/kg/day) or lanthanum carbonate (1000 mg/kg/day) by oral gavage for 12 weeks. Results. CRF animals treated with either sevelamer (500 or 1000 mg/kg/day) or lanthanum carbonate (1000 mg/kg/day) developed a phosphate depletion after 4 weeks of treatment, as evidenced by a marked reduction in phosphaturia. At sacrifice after 12 weeks of treatment, bone histomorphometry showed that a mineralization defect had developed in two out of six animals in the lanthanum-carbonate-treated group, in four out of seven animals in the 1000 mg/kg/day sevelamer group, and in one out of nine animals in the 500 mg/kg/day sevelamer group. Conclusions. These results corroborate our previous findings that the administration of a powerful phosphate-binding agent to CRF rats can induce phosphate depletion, resulting in a mineralization defect.

Lanthanum Carbonate in the Management of Renal Osteodystrophy in Dialysis Patients

In an open label, randomized, parallel group study, we treated ten patients with lanthanum carbonate and ten patients with calcium carbonate to control their serum phosphate levels. All patients were initiated onto dialysis within 12 weeks of recruitment to the study. They were on maintenance bicarbonate haemodialysis for 12 hours per week, with low flux polysulphone or hemophane membrane, and required phosphate control by the use of oral phosphate binders. Both phosphate binders were given with meal, divided into three equal doses. The maximum allowed daily dose of lanthanum carbonate and calcium carbonate was 3750 mg and 9000 mg, respectively. The duration of the study was one year. Serum phosphate levels were controlled well in both groups with no difference between them. In the lanthanum group mean phosphate level varied between 1.3 and 1.9 mmol/l, whilst in the calcium carbonate group it varied between 1.3 and 1.65 mmol/l. The maximum mean daily dose reached 1450 +/− 610 mg in the lanthanum carbonate group and 2400 +/− 1400 mg in the calcium carbonate group. In both groups, serum calcium levels did not vary significantly during the study. Mean serum calcium was 2.12 +/− 0.02 mmol/l in the lanthanum carbonate group and 2.33 +/−0.09 mmol/l in the calcium carbonate group. Bone alkaline phosphatase did not significantly vary between the two treatment groups, remaining at the upper limit of the referent values. The mean value of PTH level in the lanthanum carbonate group was 33 +/−6.2 pmol/l, and differed significantly from the mean PTH level at the calcium carbonate group –23 +/− 5.9 pmol/l (PTH ref. values 1.05– 6.84 pmol/l). In the both groups the mean levels of 25 vitamin D and 1,25 vitamin D were similar and throughout the study remained at the lower limit of the referent values. Lanthanum carbonate proved a safe phosphate binder, as we noted no serious adverse events, except for sporadic, clinically non-relevant hypocalcaemia. We could conclude that lanthanum carbonate was a safe and effective phosphate binder and it could better prevent hypercalcaemia.