Lanthanum carbonate for the treatment of hyperphosphataemia in renal failure and dialysis patients

Hyperphosphataemia is a usual accompaniment of end stage renal disease and dialysis, in the absence of dietary phosphate restriction or supplemental phosphate binders. It 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. However, phosphate control has not significantly improved over the last two decades, mainly because of the lack of an ideal oral phosphate-binding agent. Aluminium- and calcium-based agents are associated with major side effects, despite their undoubted efficacy. Although sevel-amer hydrochloride represents a step forward in the management of hyperphosphataemia, it is not an ideal phosphate binder due to its cost and tablet burden. Lanthanum carbonate is the most recent non-calcium, non-aluminium, phosphate-binding agent. It is effective and well-tolerated, and no n-egative effects on bone histology have been observed.     

Lanthanum carbonate for the treatment of hyperphosphataemia in renal failure and dialysis patients

Hyperphosphataemia is a usual accompaniment of end stage renal disease and dialysis, in the absence of dietary phosphate restriction or supplemental phosphate binders. It 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. However, phosphate control has not significantly improved over the last two decades, mainly because of the lack of an ideal oral phosphate-binding agent. Aluminium- and calcium-based agents are associated with major side effects, despite their undoubted efficacy. Although sevel-amer hydrochloride represents a step forward in the management of hyperphosphataemia, it is not an ideal phosphate binder due to its cost and tablet burden. Lanthanum carbonate is the most recent non-calcium, non-aluminium, phosphate-binding agent. It is effective and well-tolerated, and no negative effects on bone histology have been observed.     

碳酸镧对持续非卧床腹膜透析患者高磷血症的疗效观察

目的评价碳酸镧治疗持续非卧床腹膜透析(CAPD)患者高磷血症的有效性。方法选取维持性腹膜透析并高磷血症患者33例,随机分为2组。对照组16例,给予碳酸钙咀嚼片1片,2次/d;试验组17例,给予碳酸镧咀嚼片,根据患者的血磷水平调整碳酸镧剂量。治疗周期均为12周。结果治疗4、12周后,试验组血磷水平下降,且试验组低于对照组[(1.82±0.27)mmol/L vs.(2.31±0.28)mmol/L,(1.53±0.23)mmol/L vs.(2.27±0.26)mmol/L],两组比较差异有统计学意义(P<0.05);试验组i PTH水平下降,且试验组低于对照组[(813.68±357.69)pg/m L vs.(928.87±519.12)pg/m L,(613.79±148.35)pg/m L vs.(1 028.96±334.69)pg/m L],两组比较差异有统计学意义(P<0.05)。结论碳酸镧可以显著降低CAPD高磷血症患者的血磷水平。     

碳酸镧对维持性血液透析患者高磷血症的疗效及安全性

目的探讨碳酸镧对维持性血液透析患者高磷血症治疗的有效性和安全性。方法采用多中心、队列研究方式,选择符合纳入标准的维持性血透患者60例,将其分为2组,每组30例,分别使用碳酸镧或醋酸钙进行降磷治疗,观察时间为8周,定期检测各项血生化指标,记录不良反应。结果治疗前,两组透析患者血磷、血钙水平比较差异无统计学意义(P>0.05),治疗结束时,两组血磷水平均降低(P<0.05)。但治疗后2、4、8周,碳酸镧组血磷水平均低于醋酸钙组(P<0.05),血磷水平达标率(<1.78 mmol/L)高于醋酸钙组(P<0.05)。治疗结束时,碳酸镧组血钙水平与治疗前比较差异无统计学意义(P>0.05),而醋酸钙组血钙水平升高(P<0.05)。碳酸镧组的各期发生高钙血症比率及累计不良反应发生率均低于醋酸钙组(P<0.05)。结论相较于常用含钙磷结合剂醋酸钙,碳酸镧对于维持性血液透析患者具有更好的降磷效果,且高钙血症的发生率降低,可避免增加血管钙化的风险,且不增加患者的不良反应。     

碳酸镧治疗维持性血液透析患者高磷血症的短期疗效及安全性

目的观察碳酸镧治疗维持性血液透析患者高磷血症的短期疗效及安全性。方法选取维持性血液透析并高磷血症患者42例,随机分为两组,每组21例。试验组给予碳酸镧咀嚼片,根据患者的血磷值制定碳酸镧的使用剂量;对照组给予碳酸钙D_3咀嚼片,1片,bid;治疗周期均为12周。观察两组血磷、血钙、钙磷乘积、血全段甲状旁腺素水平变化及不良反应。结果试验组和对照组血磷分别于治疗2周和4周后出现下降,试验组血磷下降幅度大于对照组(P<0.05)。试验组治疗前后血钙水平无明显变化(均P>0.05),对照组治疗后血钙升高(P<0.05)。试验组钙磷乘积下降,且低于同时点对照组,差异显著(P<0.05)。试验组和对照组胃肠道反应发生率分别为29%和24%(P>0.05),高钙血症发生率分别为0和29%(P<0.05)。结论与碳酸钙相比,碳酸镧具有更快、更好的降血磷效果,且不会导致高钙血症,是治疗维持性血液透析患者高磷血症安全有效的药物。     

碳酸镧治疗维持性血液透析患者高磷血症的临床疗效

目的 探讨碳酸镧治疗维持性血液透析患者高磷血症的疗效。方法 选择2014年1月至2015年12月在连云港市第一人民医院维持性血液透析的50例患者为研究对象（透析至少6个月）,随机分为碳酸镧组（LC组）和碳酸钙组（CC组）,每组各25例,治疗4周、24周后,分别比较两组治疗前后血磷、血钙、甲状旁腺激素水平,24周后两组间钙、磷、甲状旁腺激素水平。结果 47例患者完成治疗及随访。与治疗前相比,两组患者治疗4周后的血磷水平均下降,差异有统计学意义（P<0.05）;与治疗前相比,两组患者治疗24周后的血磷水平下降,差异有统计学意义（P<0.05）。LC组整个治疗过程中血钙无明显变化,差异无统计学意义（P>0.05）,而CC组治疗24周后血钙水平升高,差异有统计学意义（P<0.05）。两组患者的甲状旁腺激素水平较治疗前下降,差异有统计学意义（P<0.05）。治疗24周后,LC组患者血磷、血钙、甲状旁腺激素水平低于CC组,差异有统计学意义（P<0.05）。结论 碳酸镧能安全有效治疗终末期肾衰透析患者高磷血症,降磷作用持久、副作用少,且更安全有效。     

醋酸钙联合碳酸镧治疗尿毒症血液透析高磷血症的疗效观察

目的探讨醋酸钙片联合碳酸镧咀嚼片治疗尿毒症血液透析患者高磷血症的临床疗效。方法选取2014年8月—2016年9月在青岛市市立医院进行尿毒症血液透析高磷血症患者134例,根据血磷水平随机分为醋酸钙组(43例)、碳酸镧组(45例)、醋酸钙和碳酸镧联合组(46例)。醋酸钙组口服醋酸钙片,2片/次,3次/d;碳酸镧组口服碳酸镧咀嚼片,2片/次,3次/d;联合组口服碳酸镧咀嚼片、醋酸钙片,2片/次,3次/d。3组患者均持续治疗12周。观察各组的临床疗效,比较各组的观察指标。结果碳酸镧组总有效率(75.5%)高于醋酸钙组(69.7%),但差异无统计学意义。联合组总有效率(94.5%)高于醋酸钙组、碳酸镧组,差异均具有统计学意义(P0.05)。治疗后,各组血磷、血甲状旁腺素(PTH)均显著降低,碳酸镧组血钙、冠状动脉钙化积分(CACs)降低,醋酸钙组、联合组血钙、CACs升高,与同组治疗前比较差异具有统计学意义(P0.05)。治疗后,与醋酸钙组比较,碳酸镧组、联合组的血磷、血钙、血PTH、CACs均降低,差异具有统计学意义(P0.05);与碳酸镧组比较,联合组的血磷、血PTH降低,血钙、CACs升高,差异具有统计学意义(P0.05)。结论碳酸镧和醋酸钙均能有效降低血磷,但碳酸镧对血钙的影响较小,并能明显延缓CACs的进展。碳酸镧联合醋酸钙控制血磷效果最好,但有增加CAC的进展的风险,有待于进一步研究。     

碳酸镧对维持性血液透析患者并继发性甲旁亢的高血磷影响

目的观察碳酸镧对维持性血液透析患者并继发性甲旁亢的高磷血症的影响。方法将31例血清全段甲状旁腺素（iFFH〉300-500pg/ml的维持性血液透析患者随机分为2组,每组均口服骨化三醇1．0ug,2次／周冲击治疗。观察组给予口服碳酸镧咀嚼片（Fosren01）500mg,3次／d,14例。对照组给予醋酸钙片667mg,3次／d,17例。结果治疗8周后观察组血磷及iFFH较治疗前明显下降,血磷较对照组有明显下降,差异有统计学意义（P〈0．05）。结论碳酸镧可有效降低MHD患者并继发性甲旁亢用骨化三醇冲击治疗时的血磷水平。     

碳酸镧应用于高磷血症维持性血液透析患者的长期临床疗效和安全性

目的评估碳酸镧长期应用于高磷血症维持性血液透析(MHD)患者的临床疗效和安全性。方法 MHD患者56例,血清磷>1.78 mmol·L-1,随机分为两组。碳酸镧组35例,予碳酸镧咀嚼片,起始剂量750 mg,bid,总剂量<3 000 mg·d-1。碳酸钙组21例,予碳酸钙D3片,起始剂量600 mg,bid,总剂量<3 000 mg·d-1。根据血磷和血钙检测结果调整药物剂量,疗程均为36个月。观察两组治疗前和治疗1、3、6、12、24、36个月患者血清钙、磷、全段甲状旁腺激素(i PTH)、成纤维细胞生长因子23(FGF-23)水平变化情况和不良反应,并在治疗前和治疗36个月行心脏彩超和螺旋CT,评估左心室肥厚和冠状动脉钙化状况。结果共39例患者完成本次研究,碳酸镧组25例,碳酸钙组14例。与治疗前比较,两组血磷水平治疗1个月起即下降(P<0.05)。碳酸镧组治疗期间血钙水平无明显变化,而碳酸钙组于治疗6个月血钙开始增高(P<0.05)。碳酸镧组i PTH水平治疗6个月起下降(P<0.05),碳酸钙组治疗期间i PTH水平无明显变化。碳酸镧组FGF-23水平治疗1个月起即下降(P<0.05),碳酸钙组于治疗12个月起下降(P<0.05)。治疗36个月,碳酸镧组血磷、钙、i PTH、FGF-23水平均低于碳酸钙组(P<0.05)。治疗前后血磷水平变化值和血FGF-23水平变化值进行相关分析,两者呈正相关(r=0.605,P<0.01)。治疗36个月,两组左心室质量指数和冠状动脉钙化评分均较治疗前上升(P<0.05),但碳酸镧组两项指标的进展幅度均小于碳酸钙组(P<0.05)。两组均无严重不良反应发生。结论对于高磷血症MHD患者,碳酸镧降血磷效果优于碳酸钙,且能同时降低血FGF-23和i PTH水平,而不引起血钙蓄积,还能够延缓MHD患者左心室肥厚和冠状动脉硬化的进展。     

Phosphate binders for the treatment of hyperphosphatemia in chronic kidney disease patients on dialysis: a comparison of safety profiles

Introduction: Hyperphosphatemia is common in the late stages of chronic kidney disease (CKD) and is associated with elevated parathormone levels, abnormal bone mineralization, extraosseous calcification and increased risk of cardiovascular events and death. Several classes of oral phosphate binders are available to help control phosphorus levels. Although effective at lowering serum phosphorus, they all have safety issues that need to be considered when selecting which one to use.

Areas covered: This paper reviews the use of phosphate binders in patients with CKD on dialysis, with a focus on safety and tolerability. In addition to the more established agents, a new resin-based phosphate binder, colestilan, is discussed.

Expert opinion: Optimal phosphate control is still an unmet need in CKD. Nonetheless, we now have an extending range of phosphate binders available. Aluminium has potentially serious toxic risks. Calcium-based binders are still very useful but can lead to hypercalcemia and/or positive calcium balance and cardiovascular calcification. No long-term data are available for the new calcium acetate/magnesium combination product. Lanthanum is an effective phosphate binder, but there is insufficient evidence about possible long-term effects of tissue deposition. The resin-based binders, colestilan and sevelamer, appear to have profiles that would lead to less vascular calcification, and the main adverse events seen with these agents are gastrointestinal effects.     

Lanthanum: new drug. Hyperphosphataemia in dialysis patients: more potential problems than benefits

(1) In dialysis patients with chronic renal failure, hyperphosphataemia can cause osteorenal dystrophy, leading to bone pain, fractures and excess cardiovascular mortality. In addition to a low-phosphorus diet and dialysis, phosphorus chelators are usually needed to control blood phosphorus levels. The first choice is calcium carbonate, and sevelamer is an alternative. (2) Lanthanum carbonate, a phosphorus chelator, is now also licensed for the treatment of hyperphosphataemia in dialysis patients with chronic renal failure. (3) In addition to three dose-finding placebo-controlled studies, clinical evaluation includes 2 comparative randomised unblinded trials: one 6-month trial versus calcium carbonate and a 2-year trial versus other phosphorus chelators. During these trials, lanthanum was no more effective than the comparators in terms of effects on the mortality rate, incidence of fractures, or blood phosphorus level. (4) During these trials, adverse events attributed to treatment were more frequent with lanthanum than with the other phosphorus chelators. The main problems were gastrointestinal disorders (nausea, vomiting, diarrhoea, constipation and abdominal pain), headaches, seizures, and encephalopathy. (5) The accumulation of lanthanum in the bones and brain is troubling. The known long-term adverse effects of aluminium, another trivalent cation with weak gastrointestinal absorption, suggest that caution is also required with lanthanum. (6) In practice, when a phosphorus chelator is needed to treat hyperphosphataemia in dialysis patients with chronic renal failure, calcium carbonate is the first choice and sevelamer remains the best alternative.     

药用炭片联合碳酸镧治疗血液透析高磷血症的临床研究

目的探讨药用炭片联合碳酸镧治疗血液透析高磷血症的临床疗效。方法选取2014年5月—2016年5月在驻马店市中心医院治疗的血液透析高磷血症患者160例,随机分为对照组(80例)和治疗组(80例)。对照组口服碳酸镧咀嚼片,1 g/次,3次/d;治疗组在对照组基础上口服药用炭片,1.5 g/次,3次/d。两组患者均经过12周。观察比较治疗前后两组患者临床疗效和血清学指标。结果治疗后,对照组和治疗组临床总有效率分别为81.25%、93.75%,两组比较差异具有统计学意义(P0.05)。治疗后,两组血磷、血钙、血甲状旁腺激素(PTH)、超敏C反应蛋白(hs-CRP)、成纤维生长因子23(FGF-23)和钙磷乘积水平均明显降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗组血清学指标低于对照组,两组比较差异具有统计学意义(P0.05)。结论药用炭片联合碳酸镧治疗血液透析高磷血症可有效改善患者生存质量,具有一定的临床推广应用价值。     

尿毒清颗粒对血液透析患者高磷血症控制作用的临床研究

目的观察尿毒清颗粒对维持性血液透析患者高磷血症的控制作用。方法选择行维持性血液透析的慢性肾脏病患者24例,患者经常规治疗其高磷血症仍控制不良。患者在保持饮食及基础治疗不变的基础上,予常规碳酸钙口服2个月后,给予口服尿毒清颗粒一日2次,每次10g,治疗2个月,观察治疗前后血磷、钙水平,钙磷乘积和iPTH变化。结果尿毒清颗粒治疗后血清磷、钙磷乘积较治疗前均明显降低（P〈0．01）,与对照期相比,治疗期血磷降低（0．22±0．23）mmol／L,钙磷乘积降低（7．30±6．91）（mg／dL）^2,差异均有统计学意义（P〈0．01）,未发现对钙和iPTH水平的影响。结论尿毒清颗粒可以有效改善高磷血症,适用于血液透析患者常规治疗后仍存在高磷血症患者的辅助治疗。     

Drug therapy in patients undergoing peritoneal dialysis. Clinical pharmacokinetic considerations

Peritoneal dialysis has become an accepted treatment modality for end-stage renal disease. The introduction of continuous ambulatory peritoneal dialysis (CAPD) has further popularised this technique. The need for adjustment of drug dosage in patients with endstage renal disease and the need for supplemental dosages following haemodialysis are well recognised. Little documentation exists concerning the need for supplemental drug dosage in patients on peritoneal dialysis. Knowledge of the influence of peritoneal dialysis on the elimination of specific drugs is essential to the rational design of dosage regimens in patients undergoing this dialysis technique. This review addresses the clinical pharmacokinetic aspects of drug therapy in patients undergoing peritoneal dialysis and considers: the efficiency of the peritoneal membrane as a dialysing membrane; the effects of peritoneal dialysis on the pharmacokinetics of drugs; the pharmacokinetic models and estimation methods for peritoneal dialysis clearance and the effects of peritoneal dialysis on drug elimination; the influence of the pharmacokinetic parameters of drugs on drug dialysability; and the application of pharmacokinetic principles to the adjustment of drug dosage regimens in peritoneal dialysis patients. Data on drugs which have been studied in peritoneal dialysis are tabulated with inclusion of pharmacokinetic and dialysability information.     

碳酸镧联用醋酸钙或碳酸钙治疗血液透析患者高磷血症的Meta分析

目的 系统评价碳酸镧联用醋酸钙或碳酸钙治疗血液透析患者高磷血症的有效性和安全性。方法 计算机检索PubMed、Embase、Cochrane图书馆,中国学术期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、维普中文期刊全文数据库（VIP）和万方数据库,纳入碳酸镧联用醋酸钙或碳酸钙治疗血液透析患者高磷血症的临床随机对照试验（RCT）,检索时限均为建库起至2020年10月,筛选文献并进行质量评价后,采用RevMan 5.3软件进行Meta分析。结果 共纳入12项RCTs,1 066例患者。Meta分析结果显示：（1）相对于醋酸钙或碳酸钙单用,碳酸镧联用醋酸钙或碳酸钙显著提高临床有效率[RR=1.32,95% CI=（1.22,1.42）,P<0.01]、降低血磷水平[MD=-0.35,95% CI=（-0.44,-0.27）,P<0.01]、血钙水平[MD=-0.17,95% CI=（-0.23,-0.11）,P<0.01]和免疫反应性甲状旁腺激素水平[MD=-50.44,95% CI=（-69.71,-31.16）,P<0.01],未显著增加不良反应发生率[RR=0.96,95% CI=（0.62,1.50）,P=0.87];（2）相对于碳酸镧单用,碳酸镧联用醋酸钙或碳酸钙显著提高临床有效率[RR=1.26,95% CI=（1.09,1.45）,P<0.01],降低血磷水平[MD=-0.24,95% CI=（-0.31,-0.17）,P<0.01]、免疫反应性甲状旁腺激素水平[MD=-30.09,95% CI=（-52.76,-7.43）,P<0.01],未增加血钙水平[MD=0.09,95% CI=（-0.04,0.23）,P=0.18]和不良反应发生率[RR=1.03,95% CI=（0.46,2.33）,P=0.94]。结论 碳酸镧联用醋酸钙或碳酸钙治疗血液透析患者高磷血症的临床疗效优于醋酸钙或碳酸钙单用和碳酸镧单用,且未显著增加不良反应发生率。     

Effect of lanthanum carbonate and calcium acetate in the treatment of hyperphosphatemia in patients of chronic kidney disease

Objectives:

The tolerability and efficacy of lanthanum carbonate has not been studied in the Indian population. This study was, therefore, undertaken to compare the efficacy and tolerability of lanthanum carbonate with calcium acetate in patients with stage 4 chronic kidney disease.

Design:

A randomized open label two group cross-over study.

Materials and Methods:

Following Institutional Ethics Committee approval and valid consent, patients with stage 4 chronic kidney disease were randomized to receive either lanthanum carbonate 500mg thrice daily or calcium acetate 667 mg thrice daily for 4 weeks. After a 4-week washout period, the patients were crossed over for another 4 weeks. Serum phosphorous, serum calcium, serum alkaline phosphatase, and serum creatinine were estimated at fixed intervals.

Results:

Twenty-six patients were enrolled in the study. The mean serum phosphorous concentrations showed a declining trend with lanthanum carbonate (from pre-drug levels of 7.88 ± 1.52 mg/dL-7.14 ± 1.51 mg/dL) and calcium acetate (from pre-drug levels of 7.54 ± 1.39 mg/dL-6.51 ± 1.38 mg/dL). A statistically significant difference was seen when comparing the change in serum calcium produced by these drugs (P < 0.05). Serum calcium levels increased with calcium acetate (from pre-drug levels of 7.01 ± 1.07-7.46 ± 0.74 mg dL), while it decreased with lanthanum carbonate (from pre-drug levels 7.43 ± 0.77-7.14 ± 0.72 mg/dL). The incidence of adverse effects was greater with lanthanum carbonate.

Conclusion:

Lanthanum carbonate and calcium acetate are equally effective phosphate binders with trends obvious in the first 4 weeks of therapy. The decrease in serum calcium levels with lanthanum carbonate when compared to the increase in serum calcium levels due to calcium acetate is statistically significant. The drawback of lanthanum carbonate is its high cost and relatively higher incidence of adverse events during treatment.     

Drug therapy in patients undergoing continuous ambulatory peritoneal dialysis. Clinical pharmacokinetic considerations

Continuous ambulatory peritoneal dialysis (CAPD) is an accepted alternative to haemodialysis in the treatment of end-stage renal failure. The frequently used intraperitoneal administration of antibiotics to treat peritonitis and the possible role of CAPD in the elimination of drugs has stimulated pharmacokinetic research in this field. The 2 principal results derived from these studies are: (1) the elimination capacity of CAPD for drugs given systemically or orally is very low, and (2) drugs administered intraperitoneally rapidly enter the circulation, a significant amount of drug being absorbed from the peritoneal cavity. This pharmacokinetic behavior is easily understood considering some basic and simple pharmacokinetic principles: the higher the volume of distribution of a substance, the lower will be the percentage of drug present in the peritoneal cavity. Thus, a prerequisite for rapid drug elimination by CAPD is a low body volume of distribution of a particular drug. Only in such a case will the drug diffuse into the peritoneal space to a significant extent. For dosing regimens in CAPD patients, the fraction of the dose eliminated by the peritoneal route should be known or estimated. This fraction depends on the relation of the peritoneal clearance to the total body clearance, and on the protein binding of the drug. The low flow rate of the peritoneal effluent (approximately 10 L/day = 7 ml/min) appears to be the most important limiting factor for the low extraction capacity of CAPD. The list of drugs that have been found to be significantly eliminated by CAPD is short: particular mention should be made of the aminoglycosides and some cephalosporins. The data on the peritoneal elimination of vancomycin are inconsistent. Although the intravenous and oral routes have been successfully used for the treatment of peritonitis, the time course of antibiotic concentrations in the peritoneal space appears to favour the peritoneal route of drug administration. During peritonitis, intraperitoneally administered drugs enter the circulation more rapidly and completely, due to the increased permeability of the peritoneal membrane. As long as the dialysate outflow rate and protein binding of the drug are not extensively altered by peritoneal inflammation, however, the extraction capacity of CAPD appears to remain low.