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Background@#Hyperphosphatemia is a risk factor associated with mortality in patients on maintenance hemodialysis. Gut absorption of phosphate is the major source. Recent studies indicated that the intestinal flora of uremic patients changed a lot compared with the healthy population, and phosphorus is an essential element of bacterial survival and reproduction. The purpose of this study was to explore the role of intestinal microbiota in phosphorus metabolism.@*Methods@#A prospective self-control study was performed from October 2015 to January 2016. Microbial DNA was isolated from the stools of 20 healthy controls and 21 maintenance hemodialysis patients. Fourteen out of the 21 patients were treated with lanthanum carbonate for 12 weeks. Thus, stools were also collected before and after the treatment. The bacterial composition was analyzed based on 16S ribosomal RNA pyrosequencing. Bioinformatics tools, including sequence alignment, abundance profiling, and taxonomic diversity, were used in microbiome data analyses. Correlations between genera and the serum phosphorus were detected with Pearson's correlation. For visualization of the internal interactions and further measurement of the microbial community, SparCC was used to calculate the Spearman correlation coefficient with the corresponding P value between each two genera.@*Results@#Thirteen genera closely correlated with serum phosphorus and the correlation coefficient was above 0.4 (P < 0.05). We also found that 58 bacterial operational taxonomic units (OTUs) were significantly different and more decreased OTUs were identified and seven genera (P < 0.05) were obviously reduced after using the phosphate binder. Meanwhile, the microbial richness and diversity presented downward trend in hemodialysis patients compared with healthy controls and more downward trend after phosphorus reduction. The co-occurrence network of genera revealed that the network complexity of hemodialysis patients was significantly higher than that of controls, whereas treatment with lanthanum carbonate reduced the network complexity.@*Conclusions@#Gut flora related to phosphorus metabolism in hemodialysis patients, and improving intestinal microbiota may regulate the absorption of phosphate in the intestine. The use of phosphate binder lanthanum carbonate leads to a tendency of decreasing microbial diversity and lower network complexity.
Subject(s)
Child , Female , Humans , Male , Middle Aged , Gastrointestinal Microbiome , Physiology , Lanthanum , Therapeutic Uses , Phosphorus , Metabolism , Prospective Studies , Renal Dialysis , Risk Factors , Uremia , Drug Therapy , Metabolism , MicrobiologyABSTRACT
OBJECTIVE:To observe clinical efficacy and safety of lanthanum carbonate in the treatment of hyperphosphatemia in uremic patients underwent maintenance hemodialysis. METHODS:A total of 142 uremic patients with hyperphosphatemia under-went maintenance hemodialysis were selected from Xinqiao Hospital of Third Military Medical University and Chongqing Banan District Hospital of TCM during Jan. 2012-Dec. 2016. They were given Lanthanum carbonate chewable tablets with initial dose of 250 mg,tid,when serum phosphate level ranged 1.78-2.26 mmol/L or with initial dose of 500 mg,tid,when serum phosphate lev-el was >2.26 mmol/L. Drug dosage was adjusted according the level of serum phosphate during treatment. After 1,2,3 months of treatment,the levels of serum phosphate,serum calcium,albumin,parathyroid hormone(PTH)and alkaline phosphatase were de-tected and the corrected product of serum calcium and calcium phosphorus was calculated. The occurrence of ADR was observed. RESULTS:After 1,2,3 months of treatment,the levels of serum phosphate and the product of serum calcium and calcium phos-phorus were all decreased significantly compared to before trreatment,with statistical significance (P0.05). Total response rate was 93.7%. There were 19 cases of patients with mild adverse reactions. CONCLU-SIONS:Lanthanum carbonate in the treatment of hyperphosphatemia in uremic patients underwent maintenance hemodialysis shows good clinical response rate,can significantly reduce the levels of serum phosphate and the product of serum calcium and calcium phosphorus with good safety.
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Objective To assess the treatment efficacy and safety of lanthanum carbonate (LC) in patients on maintenance hemodialysis. Methods MEDLINE (1996—2014), Embase (1974—2014.12), Pubmed (1996—2014.12), Cochrane library, Chinese Wanfang database (1996—2014.12) and CNKI (1979—2014.12) were searched. Lanthanum carbonate and hemodialysis were used as Chinese and English search terms respectively, and the articles met the inclusion and exclusion criteria were used as supplements. Quality assessment and data mining were conducted by two independent investigators who performed Meta-analysis using RevMan5.2. Results Nine trials with 2 674 participants were included in this study. The Meta-analysis showed that there were similar blood levels of calcium [WMD=-0.24,95%CI:(-0.61)-0.14, P=0.21], phosphorus [WMD=0.14,95%CI:(-0.02)-0.30,P=0.08] and phosphate control rates (RR=0.91,95%CI:0.70-1.17, P=0.44) between control group and lanthanum carbonate group. There were lower incidence rates of hypercalcemia (RR=0.17, 95%CI:0.06-0.47, P=0.000 7) and blood levels of calcium-phosphorus product [WMD=-2.17,95%CI:(-3.99)-(-0.35), P=0.02], and higher levels of parathyroid hormone (iPTH, WMD=105.69, 95%CI:70.38-141.00, P<0.000 01) and bone-specific alkaline phosphatase (BAP, WMD=6.47, 95%CI:0.43-12.50, P=0.04) in these two groups. There were no significant differences in incidence rates of gastrointestinal adverse events between two groups. Conclusion Lanthanum carbonate should be used as preferred choice of phosphate binders to control serum phosphorus in patients on maintenance hemodialysis.
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Objective To assess the efficacy and adverse reaction of Lanthanum carbonate in patients with hyperphosphatemia and high calcium times phosphate product receiving maintenance hemodialysis.Methods Twenty-three hemodialysis patients with serum phosphate ≥ 2.0 mmol/L and/or the serum calcium times phosphate product ≥ 4.52 mmol2/L2 were prescribed Lanthanum carbonate chewed with meals for 4 weeks.Blood (Hb), serum albumin (ALB), alanine amino shift enzyme (ALT), aspartic acid transaminase (AST) ,calcium(CA), phosphorus (P) calculated the product of calcium and phosphorus (Ca×P) and intact parathyroid hormone (iPTH) level were checked before and after Lantharum carbonate therapy.The adverse reactions were recorded concomitantly.Results Serum phosphate and the serum calcium time phosphate product significantly decreased after 1 month Lanthanum carbonate therapy((2.48±0.55) mmol/L vs.(1.83 ±0.37) mmol/L, (5.21 ± 1.35) mmol2/L2 vs.(4.10±0.96) mmol2/L2;t =2.742,2.936;P＜0.05).Serum calcium, iPTH level and blood cells count remained no change(P＞0.05), while serum ALT, AST concentration within normal range.Five patients complained affordable abdomen discomfort or upset.Conclusion Lantharum carbonate show to effectively and quickly control serum phosphorus levels and calcium time phosphate product in hemodialysis patients without inducing changes in serum calcium and should be considered an ideal phosphate binder.
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Objective To assess the efficacy and safety of lanthanum carbonate in treatment of hyperphosphatemia in end-stage renal disease (ESRD).Methods Randomized controlled trails of lanthanum carbonate in treatment of hyperphosphatemia in ESRD patients were searched in the database of MEDLINE,Cochrane Central Register of Controlled Trials,EMBASE,CNKI,Wanfang database.Data extracted from the literatures were analyzed with the Cochrane Collaboration's RevMan 5.1 software.Results Lanthanum carbonate group was similar with calcium carbonate group in treating hyperphosphatemia[RR =1.00,95 ％ CI (0.92-1.09),P =0.97],and more effective than placebo [RR=4.69,95％ CI (2.63-8.39),P＜ 0.01] (intervention dose≤ 1500 mg) and [RR =18.92,95％ CI (7.42-48.22),P ＜ 0.01] (intervention dose ＞ 1500 mg).In comparison with calcium carbonate group,the incidence of hypercalcinemia of lanthanum carbonate group was lower [RR =0.06,95 ％ CI (0.01-0.72),P =0.03],while the incidence of nausea [RR =1.80,95 ％ CI(0.70-4.64),P =0.22],vomiting [RR =3.94,95％ CI (0.45-34.38),P=0.22] and constipation [RR=0.82,95％ CI (0.49-1.37),P=0.45] were similar.The incidence of nausea and vomiting of lanthanum carbonate group were similar with placebo,with lower incidence of constipation [RR =0.19,95 ％ CI (0.06-0.59),P ＜ 0.01].Conclusions The efficacy of lanthanum carbonate in treating hyperphosphatemia is similar with calcium carbonate.The incidence of hypercalcinemia of lanthanum carbonate is lower than that of calcium carbonate,and the incidence of gastrointestinal adverse effect such as nausea,vomiting and constipation are similar with calcium carbonate.
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Objective To assess the effect and safety of lanthanum carbonate vs conventional phosphate binders for hyperphosphatemia in patients undergoing maintenance hemodialysis.Methods According to the collaborative search strategy,MEDLINE (1996 to 2012.12),EBCO (1996 to 2012.12),the clinical control test database of Cochrane Library and Chinese Wanfang database (1996to 2012.12) were searched.Related literature,whether Published or not and meeting summary included,were searched by hand.Quality assessment and data extraction were conducted by two independent investigators.Meta-analysis was conducted by RevMan 5.0.The following outcomes were assessed:serum phosphorus levels,serum iPTH levels,serum calcium levels and adverse events.Results were expressed as OR with 95％ confidence interval for dichotomous outcomes and WMD with 95％ confidence interval for continuous outcomes.Results A total of 10 reports were identified which met the inclusion criteria.The meta-analysis showed that the efficacy of treating hyperparathyroidism in hemodialysis patients was similar between lanthanum carbonate and conventional phosphate binders (WMD =-0.06,95％ CI-0.27 to 0.15,P =0.57) and the incidences of discontinuing due to adverse events were also similar.However,there were fewer hypercalcemic episodes and lower serum calcium levels in the lanthanum carbonate group compared to calcium-based phosphorus binders group.Conclusion Lanthanum carbonate is effective and well tolerated in treating hyperphosphatemia in hemodialysis patients with fewer hypercalcemia and lower serum calcium levels compared to calciumbased phosphate binders.
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PURPOSE: Hyperphosphatemia and renal osteodystrophy increase the mortality and morbidity in chronic kidney disease. We compared the effects of lanthanum carbonate (LC) and calcium carbonate (CC) on phosphate homeostasis and bone bio-markers in hemodialysis patients. METHODS: The Korean dialysis patients with serum phosphorus more than 5.6 mg/dL were randomized to LC (n=12) or CC (n=11). Serum calcium, phosphorus, intact PTH, bone alkaline phosphatase, and osteocalcin were checked at regular intervals for 6 months. RESULTS: The reduction of serum phosphorus and calcium x phosphorus product at 24-week (wk) from baseline values was similar in LC and CC groups (Phosphorus: baseline, 7.28+/-1.04 mg/dL vs 7.41+/- 1.39 mg/dL, p=NS; at 24-wk, 5.39+/-1.85 mg/dL vs 5.67+/-1.43 mg/dL, p=NS) (Calcium x phosphorus product: baseline, 64.5+/-11.1 mg2/dL2 vs 61.3+/-11.9 mg2/dL2, p=NS; at 24-wk, 47.9+/-14.5 mg2/dL2 vs 51.8+/-14.0 mg2/dL2, p=NS). Despite higher baseline serum calcium levels in LC group, the changes of serum calcium from the baseline at 24-wk were significantly higher in CC group (LC vs CC; 0.23+/-0.38 mg/dL vs 0.94+/-0.87 mg/dL, p<0.05). Bone bio-markers, including iPTH, bone ALP, and osteocalcin, were comparable in 2 groups. However, significant gastrointestinal side effects leading to discontinuing the study were predominantly observed in LC (LC vs CC; n=5/12 vs n=0/11). CONCLUSION: Compared to calcium carbonate, lanthanum carbonate has similar efficacy to reduce serum phosphorus level, but less tendency to increase serum calcium level. However, the high incidence of gastrointestinal side effects in lanthanum carbonate needs further investigation in its correlation to Korean.