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 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.

scholarly journals Anti-Acid Drug Treatment Induces Changes in the Gut Microbiome Composition of Hemodialysis Patients

2021 ◽  
Vol 9 (2) ◽  
pp. 286
Author(s):  
Yi-Ting Lin ◽  
Ting-Yun Lin ◽  
Szu-Chun Hung ◽  
Po-Yu Liu ◽  
Ping-Hsun Wu ◽  
...  
Keyword(s):  
Random Forest ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Hemodialysis Patients ◽  
Microbiota Composition ◽  
Microbial Composition ◽  
Linear Discriminant ◽  
H2 Blocker ◽  
Α Diversity ◽  
16S Rna

Anti-acid drugs, proton pump inhibitor (PPI) and histamine-2 blocker (H2-blocker), are commonly prescribed to treat gastrointestinal disorders. These anti-acid drugs alter gut microbiota in the general population, but their effects are not known in hemodialysis patients. Hence, we investigated the microbiota composition in hemodialysis patients treated with PPIs or H2-blocker. Among 193 hemodialysis patients, we identified 32 H2-blocker users, 23 PPI users, and 138 no anti-acid drug subjects. Fecal samples were obtained to analyze the gut microbiome using 16S RNA amplicon sequencing. Differences in the microbial composition of the H2-blocker users, PPI users, and controls were assessed using linear discriminant analysis effect size and the random forest algorithm. The species richness or evenness (α-diversity) was similar among the three groups, whereas the inter-individual diversity (β-diversity) was different between H2-blocker users, PPI users, and controls. Hemodialysis patients treated with H2-blocker and PPIs had a higher microbial dysbiosis index than the controls, with a significant increase in the genera Provetella 2, Phascolarctobacterium, Christensenellaceae R-7 group, and Eubacterium oxidoreducens group in H2-blocker users, and Streptococcus and Veillonella in PPI users. In addition, compared to the H2-blocker users, there was a significant enrichment of the genera Streptococcus in PPI users, as confirmed by the random forest analysis and the confounder-adjusted regression model. In conclusion, PPIs significantly changed the gut microbiota composition in hemodialysis patients compared to H2-blocker users or controls. Importantly, the Streptococcus genus was significantly increased in PPI treatment. These findings caution against the overuse of PPIs.

scholarly journals Gut Microbiome-Derived Uremic Toxin Levels in Hemodialysis Patients on Different Phosphate Binder Therapies

2021 ◽  
pp. 1-10
Author(s):  
Lin-Chun Wang ◽  
Leticia M. Tapia ◽  
Xia Tao ◽  
Joshua E. Chao ◽  
Ohnmar Thwin ◽  
...  
Keyword(s):  
Liver Function ◽  
Gut Microbiome ◽  
Phosphate Binder ◽  
Serum Levels ◽  
Colonic Transit ◽  
Serum Phosphorus ◽  
Phosphate Binders ◽  
Uremic Toxin ◽  
Sevelamer Carbonate ◽  
Patient Reported

<b><i>Introduction:</i></b> Constipation is prevalent in patients with kidney failure partly due to the use of medication, such as phosphate binders. We hypothesized that serum levels of gut microbiome-derived uremic toxins (UTOX) may be affected by the choice of phosphate binder putatively through its impact on colonic transit time. We investigated two commonly prescribed phosphate binders, sevelamer carbonate (SEV) and sucroferric oxyhydroxide (SFO), and their association with gut microbiome-derived UTOX levels in hemodialysis (HD) patients. <b><i>Methods:</i></b> Weekly blood samples were collected from 16 anuric HD participants during the 5-week observational period. All participants were on active phosphate binder monotherapy with either SFO or SEV for at least 4 weeks prior to enrollment. Eight UTOX (7 gut microbiome-derived) and tryptophan were quantified using liquid chromatography-mass spectrometry. Serum phosphorus, nutritional, and liver function markers were also measured. For each substance, weekly individual levels, the median concentration per participant, and differences between SFO and SEV groups were reported. Patient-reported bowel movements, by the Bristol Stool Scale (BSS), and pill usage were assessed weekly. <b><i>Results:</i></b> The SEV group reported a 3.3-fold higher frequency of BSS stool types 1 and 2 (more likely constipated, <i>p</i> &#x3c; 0.05), whereas the SFO group reported a 1.5-fold higher frequency of BSS stool types 5–7 (more likely loose stool and diarrhea, not significant). Participants in the SFO group showed a trend toward better adherence to phosphate binder therapy (SFO: 87.6% vs. SEV: 66.6%, not significant). UTOX, serum phosphorus, nutritional and liver function markers, and tryptophan were not different between the two groups. <b><i>Conclusion:</i></b> There was no difference in the gut microbiome-derived UTOX levels between phosphate binders (SFO vs. SEV), despite SFO therapy resulting in fewer constipated participants. This pilot study may inform study design of future clinical trials and highlights the importance of including factors beyond bowel habits and their association with UTOX levels.

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.

scholarly journals Plasma Zinc Decreases in Hemodialysis Patients Treated with Calcium Carbonate as the Phosphate Binder

Nephron ◽  
1989 ◽  
Vol 53 (4) ◽  
pp. 384-385 ◽  
Author(s):  
Paolo Gilli ◽  
Dino Docci ◽  
Leopoldo Baldrati ◽  
Fausto Turci
Keyword(s):  
Calcium Carbonate ◽  
Phosphate Binder ◽  
Hemodialysis Patients ◽  
Plasma Zinc

Oral Low-Dose Ferric Citrate Is a Useful Iron Source for Hyperphosphatemic Hemodialysis Patients: A Case Series

2016 ◽  
Vol 43 (1-3) ◽  
pp. 97-100 ◽  
Author(s):  
Masayuki Tanemoto ◽  
Yu Ishimoto ◽  
Hisako Saito
Keyword(s):  
Phosphate Binder ◽  
Low Dose ◽  
Transferrin Saturation ◽  
Case Series ◽  
Ferric Citrate ◽  
Phosphate Binders ◽  
Iron Stores ◽  
Median Serum ◽  
Iron Deficient ◽  
Iron Parameters

Background: Randomized trials have demonstrated that a phosphate binder ferric citrate (FeC) increases iron parameters in comparison with other phosphate binders, but the doses for FeC to improve iron stores safely have not been clarified. Methods: We examined changes of iron parameters and blood hemoglobin (Hb) in 7 iron-deficient hemodialysis (HD) patients taking FeC 750 mg/day as a phosphate binder. Results: The median serum transferrin saturation and ferritin increased from 13% (interquartile range (IQR) 7-18) to 28% (IQR 22-31; p = 0.010) and from 17 ng/ml (IQR 11-60) to 106 ng/ml (IQR 58-176; p = 0.015) by 2 and 3 months respectively. With the persistence of these levels thereafter, the FeC administration reduced the usage of erythropoiesis-stimulating agents while maintaining adequate blood Hb levels. Conclusion: Oral FeC 750 mg/day improves iron stores without inducing iron overload in hyperphosphatemic HD patients.

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