scholarly journals A comparison between the combined effect of calcium carbonate with sucroferric oxyhydroxide and other phosphate binders: an in vitro and in vivo experimental study

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Atsushi Yaguchi ◽  
Kenji Akahane ◽  
Kumi Tsuchioka ◽  
Saori Yonekubo ◽  
Shota Yamamoto ◽  
...  
Keyword(s):  
Calcium Carbonate ◽  
Lanthanum Carbonate ◽  
Combined Effect ◽  
Ferric Citrate ◽  
Phosphate Binders ◽  
Phosphate Solution ◽  
Phosphate Binding ◽  
Sevelamer Hydrochloride

Abstract Background Approximately 30% of patients on dialysis received combination therapy for their phosphate binder prescription; however, few studies for combined effects of phosphate binders are reported. For the purpose of evaluating the efficacy of combination therapy, we compared the efficacy of sucroferric oxyhydroxide (PA21) combined with calcium carbonate with that of lanthanum carbonate hydrate, sevelamer hydrochloride, and ferric citrate hydrate combined with calcium carbonate. Methods For in vitro studies, calcium carbonate and the other phosphate binders alone or in combination were stirred in phosphate solution at pH 2–8 for 2 h. After centrifuging the suspension, the phosphorus level in the supernatant was determined. For in vivo studies, rats were orally administered calcium carbonate and the other phosphate binders (except for sevelamer hydrochloride) alone or in combination, followed by oral administration of phosphate solution adjusted to pH 2 or 7. Serum samples were collected from the rats at predetermined timepoints and the serum phosphorus levels were determined and analyzed using a two-way analysis of variance. Results In the in vitro study, the measured phosphate-binding capacity of combining sevelamer hydrochloride, PA21, and lanthanum carbonate hydrate with calcium carbonate was approximately equal to or greater than the theoretical values under most conditions. Furthermore, these combined effects were insensitive to pH in that order. The measured phosphate-binding capacity of ferric citrate hydrate combined with calcium carbonate was smaller than the theoretical values, and the combination did not exhibit efficacy under any of the tested conditions. In the in vivo study, the combined effect of PA21 and calcium carbonate at both pH values and that of lanthanum carbonate hydrate and calcium carbonate at pH 2 were additive. In contrast, the combined effect of lanthanum carbonate hydrate and calcium carbonate at pH 7 and that of ferric citrate hydrate and calcium carbonate at pH 2 were antagonistic. Conclusions These results suggest that coadministration of PA21 and calcium carbonate showed good and relatively stable efficacy throughout the range of the gastrointestinal pH and that combining lanthanum carbonate hydrate and ferric citrate hydrate with calcium carbonate may not produce the expected efficacy under certain conditions.

Comparison of Phosphate Binding Capacities of PA21, A Novel Phosphate Binder, with those of other Phosphate Binders in vitro and in vivo

Drug Research ◽  
2016 ◽  
Vol 66 (05) ◽  
pp. 262-269 ◽  
Author(s):  
A. Yaguchi ◽  
S. Yonekubo ◽  
I. Maruyama ◽  
S. Tatemichi ◽  
K. Maruyama ◽  
...  
Keyword(s):  
Phosphate Binder ◽  
Phosphate Binders ◽  
Phosphate Binding

Effects of Anion Exchange Resin as Phosphate Binder on Serum Phosphate and Ipth Levels in Normal Rats

2000 ◽  
Vol 23 (4) ◽  
pp. 243-249 ◽  
Author(s):  
H. Inoue ◽  
M. Kagoshima ◽  
K. Kaibara
Keyword(s):  
Anion Exchange ◽  
Phosphate Solution ◽  
Phosphate Binding ◽  
Phosphorus Excretion ◽  
Dietary Phosphorus ◽  
Anion Exchange Resins ◽  
Fecal Phosphorus ◽  
Exchange Resins

In order to investigate the characteristics of anion exchange resins that may safely and effectively bind dietary phosphate in digestive tract, phosphate binding experiments were carried out in vitro and in vivo with normal rats by comparing anion exchange resins, PAA-B (which has the same chemical structure as Sevelamer® HCl) and Dowe 1x8, with CaCO3. In in vitro phosphate binding experiments, PAA-B bound 32.3% less phosphate than CaCO3 at pH 7. In the rat dietary phosphorus excretion experiments, PAA-B, Dowex 1x8, and CaCO3 increased fecal phosphorus excretion by 62.7, 32.3, and 84.0%, respectively. Famotidine significantly reduced the phosphate binding of CaCO3. When phosphate solution was orally adiministered, PAA-B depressed serum phosphorus augmentations immediately after administration and thereafter effectively depressed serum iPTH. This suggests that anion exchange resins with most primary and secondary amino type anion exchange groups, have bright prospects in the treatment of hyperphosphatemia. (Int J Artif Organs 2000; 23: 243–9)

Relative in Vitro Efficacy of the Phosphate Binders Lanthanum Carbonate and Sevelamer Hydrochloride

2007 ◽  
Vol 96 (10) ◽  
pp. 2818-2827 ◽  
Author(s):  
Valerie Autissier ◽  
Stephen J.P. Damment ◽  
Richard A. Henderson
Keyword(s):  
Lanthanum Carbonate ◽  
Phosphate Binders ◽  
Sevelamer Hydrochloride

P0272COMPARATIVE GUT MICROBIOME DIFFERENCES BETWEEN FERRIC CITRATE AND CALCIUM CARBONATE PHOSPHATE BINDER TREATMENT IN HEMODIALYSIS PATIENTS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ping-Hsun Wu ◽  
Yi-Ting Lin ◽  
Po-Yu Liu ◽  
Mei-Chuan Kuo ◽  
Yi wen Chiu
Keyword(s):  
Calcium Carbonate ◽  
Gut Microbiome ◽  
Phosphate Binder ◽  
Hemodialysis Patients ◽  
Ferric Citrate ◽  
Phosphate Binders ◽  
Uremic Toxin ◽  
Phosphate Binding ◽  
Microbial Composition ◽  
Linear Discriminant

Abstract Background and Aims Gut microbiome alteration increases uremic toxin levels inducing chronic inflammation and leading morbidity and mortality in patients with chronic kidney disease. Phosphate-binding agents may potentially change the composition of the gut microbiota. However, the limited clinical study investigates the microbiome difference between iron-containing and calcium-containing phosphate binders. The aim of this study was to compare the microbiota composition in hemodialysis patients treated with ferric citrate or calcium carbonate. Method The stool microbiota was investigated in hemodialysis patients with ferric citrate used (n=8) and calcium carbonate used (n=46) by 16S rRNA next-generation gene sequencing profiling. The altered microbiota between two different phosphate binders was analyzed. Differences in the microbial composition of the two patient groups were assessed using linear discriminant analysis effect size. Results Hemodialysis patients with calcium carbonate used revealed significantly reduced microbial species diversity (Shannon index and Simpson index) and increased microbial dysbiosis index compared with ferric citrate users. Compared to patients taking calcium carbonate, a distinct microbial community structure in patients taking ferric citrate, with an increased abundance of Bacteroidetes phylum and decreased abundance of phylum Firmicutes. In comparison between two phosphate binder users, members of the order Lactobacillales were prominent in calcium carbonate therapy, including family Streptococcaceae and genus Streptococcus. In contrast, taxa of the genus Ruminococcaceae, Flavonifractor, and Cronobacter were enriched in ferric citrate phosphate binder users. Conclusion The fecal microbiota was richer and more diverse in the ferric citrate group than in the calcium carbonate group. Hemodialysis patients with ferric citrate used were associated with differences in the gut microbiome composition compared to calcium carbonate users.

scholarly journals Comparative Gut Microbiome Differences between Ferric Citrate and Calcium Carbonate Phosphate Binders in Patients with End-Stage Kidney Disease

2020 ◽  
Vol 8 (12) ◽  
pp. 2040
Author(s):  
Ping-Hsun Wu ◽  
Po-Yu Liu ◽  
Yi-Wen Chiu ◽  
Wei-Chun Hung ◽  
Yi-Ting Lin ◽  
...  
Keyword(s):  
Calcium Carbonate ◽  
Kidney Disease ◽  
Gut Microbiome ◽  
Phosphate Binder ◽  
Hemodialysis Patients ◽  
Ferric Citrate ◽  
Phosphate Binders ◽  
Rrna Gene ◽  
Phosphate Binding ◽  
Linear Discriminant

Gut dysbiosis in patients with chronic kidney disease (CKD) may induce chronic inflammation and increase morbidity. Phosphate-binding agents, generally used in patients with CKD, may potentially change the composition of the gut microbiota. This study aimed to compare the microbiota composition in hemodialysis patients treated with ferric citrate or calcium carbonate. The stool microbiota was investigated in hemodialysis patients treated with ferric citrate (n = 8) and calcium carbonate (n = 46) using 16S rRNA gene amplicon sequencing profiling using linear discriminant analysis of effect size. Further predictive functional profiling of microbial communities was obtained with Tax4Fun in R. Hemodialysis patients treated with calcium carbonate had a significantly reduced microbial species diversity (Shannon index and Simpson index) and an increased microbial alteration ratio compared with patients treated with ferric citrate. A distinct microbial community structure was found in patients treated with ferric citrate, with an increased abundance of the Bacteroidetes phylum and a decreased abundance of the phylum Firmicutes. Members of the order Lactobacillales were enriched in patients treated with calcium carbonate, whereas taxa of the genera Ruminococcaceae UCG-004, Flavonifractor, and Cronobacter were enriched in patients treated with ferric citrate phosphate binder. In conclusion, Ferric citrate therapy results in a more diverse microbiome community compared to calcium carbonate therapy in hemodialysis patients with phosphate binder treatment. The gut microbiome reflects the phosphate binder choice in hemodialysis patients, further affecting the physiological environment in the gastrointestinal tract.

scholarly journals Clinical and pharmacoeconomic profile of lanthanum carbonate treatment of hyperphosphataemia in chronic renal dialysis patients

2010 ◽  
Vol 11 (1) ◽  
pp. 13-26
Author(s):  
Mario Eandi
Keyword(s):  
Calcium Carbonate ◽  
Phosphate Binder ◽  
Cost Effective ◽  
Lanthanum Carbonate ◽  
The Body ◽  
Serum Phosphorus ◽  
Recent Analysis ◽  
Phosphate Binders ◽  
Phosphate Binding ◽  
Metastatic Calcification

Hyperphosphatemia is recognized as a principal mineral disorder in chronic kidney disease (CKD) that leads to the development of secondary hyperparathyroidism. Approximately 70% of patients with end-stage renal disease (ESRD) and dialysis have hyperphosphataemia, which is associated with renal osteodystrophy, metastatic calcification and increased mortality and morbidity. Despite dietary restriction and dialysis, most patients will require a phosphate-binding agent to treat this condition.Lanthanum carbonate is an new, potent, selective, no-resin, non-calcium phosphate binder that retains high affinity for phosphate over a wide pH range, does not bind bile acids or contribute to metabolic acidosis. Taken with food, it is well tolerated. It is poorly absorbed and does not require functioning kidneys to be removed from the body. There is no evidence from current studies that it accumulates to biologically significant levels in tissues. Lanthanum carbonate has been shown in clinical studies of up to 6 years to be an effective, well-tolerated phosphate binder. Lanthanum carbonate controls hyperphosphataemia without increasing calcium intake above guideline targets and has the potential to reduce pill burden and increase patient compliance compared with other phosphate binders. Reported adverse effects are mainly gastrointestinal, and do not differ from those of calcium carbonate. The new phosphate binders, lanthanum carbonate and sevelamer, have increased the possibilities for serum phosphate control, at the expenses of significant increases in costs. The cost-effectiveness of lanthanum carbonate has been assessed by three different studies. A recent analysis, conducted on the perspective of the UK NHS, shows it is cost-effective to follow current treatment guidelines and treat all patients who are not adequately maintained on calcium carbonate (serum phosphorus above 5.6 mg/dl) with second-line lanthanum carbonate. This is particularly the case for patients with serum phosphorus above 6.6 mg/dl. A retrospective analysis, performed on IHCSI data base (USA), and a prospective study conducted in Spain show that lanthanum carbonate is cost-effective as compared with sevelamer, requiring less number of tablets, a fact that might improve adherence, and that probably explains better results with lower costs.

Cytotoxicity Studies of Curcumin Loaded-Cockle Shell-Derived Calcium Carbonate Nanoparticles

2019 ◽  
Vol 09 ◽  
Author(s):  
Maryam Muhammad Mailafiya ◽  
Mohamad Aris Mohd Moklas ◽  
Kabeer Abubakar ◽  
Abubakar Danmaigoro ◽  
Samaila Musa Chiroma ◽  
...  
Keyword(s):  
Calcium Carbonate ◽  
Safety Margin ◽  
Bone Diseases ◽  
In Vivo Studies ◽  
Normal Cells ◽  
Cytotoxicity Studies ◽  
Standard Techniques ◽  
Cockle Shell

Background: Cockle shell-derived calcium carbonate nanoparticles (CSCaCO3NP) are natural biogenic inorganic material that is used in drug delivery mainly as a bone-remodeling agent as well as a delivery agent for various therapeutics against bone diseases. Curcumin possess wide safety margin and yet puzzled with the problem of poor bioavailability due to insolubility. Propounding in vitro and in vivo studies on toxicity assessments of newly synthesized nanoparticles are ongoing to overcome some crucial challenges regarding their safety administration. Nanotoxicology has paved ways for concise test protocols to monitor sequential events with regards to possible toxicity of newly synthesized nanomaterials. The development of nanoparticle with no or less toxic effect has gained tremendous attentions. Objective: This study aimed at evaluating the in vitro cytotoxic effect of curcumin-loaded cockle shell-derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) and assessing its biocompatibility on normal cells using standard techniques of WST’s assay. Method: Standard techniques of WST’s assay was used for the evaluation of the biocompatibility and cytotoxicity. Result: The result showed that CSCaCO3NP and Cur-CSCaCO3NP possess minimal toxicity and high biocompatibility on normal cells even at higher dose of 500 µg/ml and 40 µg/ml respectively. Conclusion: CSCaCO3NP can be termed an excellent non-toxic nanocarrier for curcumin delivery. Hence, curcumin loaded cockle shell derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) could further be assessed for various in vivo and in vitro therapeutic applications against various bone related ailments.

Structural characterization of amorphous calcium carbonate-binding protein: an insight into the mechanism of amorphous calcium carbonate formation

2013 ◽  
Vol 453 (2) ◽  
pp. 179-186 ◽  
Author(s):  
Jingtan Su ◽  
Xiao Liang ◽  
Qiang Zhou ◽  
Guiyou Zhang ◽  
Hongzhong Wang ◽  
...  
Keyword(s):  
Calcium Carbonate ◽  
Binding Sites ◽  
Binding Protein ◽  
Homology Modelling ◽  
Size Exclusion ◽  
Structural Basis ◽  
Amorphous Calcium Carbonate ◽  
Carbonate Formation

ACC (amorphous calcium carbonate) plays an important role in biomineralization process for its function as a precursor for calcium carbonate biominerals. However, it is unclear how biomacromolecules regulate the formation of ACC precursor in vivo. In the present study, we used biochemical experiments coupled with bioinformatics approaches to explore the mechanisms of ACC formation controlled by ACCBP (ACC-binding protein). Size-exclusion chromatography, chemical cross-linking experiments and negative staining electron microscopy reveal that ACCBP is a decamer composed of two adjacent pentamers. Sequence analyses and fluorescence quenching results indicate that ACCBP contains two Ca2+-binding sites. The results of in vitro crystallization experiments suggest that one Ca2+-binding site is critical for ACC formation and the other site affects the ACC induction efficiency. Homology modelling demonstrates that the Ca2+-binding sites of pentameric ACCBP are arranged in a 5-fold symmetry, which is the structural basis for ACC formation. To the best of our knowledge, this is the first report on the structural basis for protein-induced ACC formation and it will significantly improve our understanding of the amorphous precursor pathway.

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