Management of hyperphosphataemia in dialysis patients: role of phosphate binders in the elderly

Phosphorus control remains a relevant clinical problem in dialysis patients. With age, however, serum phosphorus level decreases significantly because of a spontaneous decrease in protein intake. Older patients usually need lower doses of phosphorus binders. Nevertheless, hyperphosphataemia is observed in a quarter of patients aged >65 years. Phosphorus retention is related to an imbalance between phosphorus intake and removal by dialysis, and is usually aggravated when vitamin D analogues are employed. Hyperphosphataemia induces secondary hyperparathyroidism and the development of osteitis fibrosa. Recent publications describe an association between phosphorus retention and increased calcium and phosphorus product (Ca2+ x P), with significant progression of tissue calcification and higher mortality risk. Dietary intervention, phosphorus removal during dialysis and phosphorus binders are current methods for the management of hyperphosphataemia. However, the phosphorus removed by standard haemodialysis is insufficient to achieve a neutral phosphorus balance when protein intake is >50 g/day. Additional protein restriction may impose the risk of a negative protein balance. More frequent dialysis may help to control resistant hyperphosphataemia. Phosphorus binders constitute the mainstay of serum phosphorus level control in end-stage renal disease patients. Aluminium-based phosphorus binders, associated with toxic effects, have largely been substituted by calcium-based phosphorus binders. However, widespread use of calcium-based phosphorus binders has evidenced the frequent appearance of hypercalcaemia and long-term progressive cardiovascular calcification. Sevelamer, a relatively new phosphorus binder, has proved efficacious in lowering serum phosphorus and parathyroid hormone (PTH) levels without inducing hypercalcaemia. Furthermore, several investigators have reported that sevelamer may prevent progression of coronary calcification. However, its efficacy in severe cases of hyperphosphataemia remains to be confirmed in large series. There are no specific guidelines for phosphorus control in the elderly. Until more information is available, levels of mineral metabolites should be targeted in the same range as those recommended for the general population on dialysis (calcium 8.7-10.2 mg/dL, phosphorus 3.5-5.5 mg/dL and Ca2+ x P 50-55 mg2/dL2). PTH values over 120 ng/L help to avoid adynamic bone disease. Since elderly patients have a higher incidence of adynamic bone (which buffers less calcium) and vascular calcification, sevelamer should be the phosphorus binder of choice in this population; but sevelamer is costly and its long-term efficacy has not been definitively validated. Patients with low normal levels of calcium may receive calcium-based phosphorus binders with little risk. Patients with low values of PTH and high normal calcium should receive sevelamer. Tailored combinations of calcium-based phosphorus binders and sevelamer should be considered, and calcium dialysate concentration adjusted accordingly.     

Sevelamer therapy for pediatric end-stage renal disease

Sevelamer, a non-calcium-containing, non-aluminum-containing phosphate binder, is frequently prescribed for treatment in adults with hyperphosphatemia secondary to end-stage renal disease (ESRD). However, published information regarding sevelamer use in children younger than 11 years is lacking. We report the use of sevelamer as a phosphate binder in a 19-month-old girl with ESRD who was receiving calcium carbonate 1250 mg 3 times/day for hyperphosphatemia. The patient's initial serum phosphorus concentration was 8.6 mg/dl, and the calcium-phosphorus product was 75 mg(2)/dl(2). This was well above the level that places patients at risk for complications such as joint, vessel, and soft-tissue calcification. An aluminum-containing phosphate binder was not an option given the patient's renal disease and the concern for neurotoxicity. Sevelamer was considered, but a MEDLINE search revealed no pediatric dosing information. An initial dosage of 100 mg/kg/day divided every 8 hours was administered, as extrapolated from adult data, and then titrated to 130 mg/kg/day divided every 8 hours based on the patient's response. The child's dietary phosphorus intake remained constant throughout her hospital stay. During sevelamer therapy, her serum phosphorus concentration dropped as low as 5.2 mg/dl; at discharge it was 6.5 mg/dl, with a corresponding calcium-phosphorus product in the upper 50s. No adverse effects associated with sevelamer were observed. In the dosages we used, sevelamer resulted in an acceptable calcium-phosphorus product and returned the patient's serum phosphorus concentration to near normal. Sevelamer appears to be a viable option as a phosphate binder in children with ESRD.     

Safety of new phosphate binders for chronic renal failure.

Phosphate (Pi) retention is a common problem in patients with chronic kidney disease, particularly in those who have reached end-stage renal disease (ESRD). In addition to causing secondary hyperparathyroidism and renal osteodystrophy, recent evidence suggests that, in ESRD patients, high serum phosphorus concentration and increased calcium and phosphorous (Ca x P) product are associated with vascular and cardiac calcifications and increased mortality. Dietary phosphorus restriction and Pi removal by dialysis are not sufficient to restore Pi homeostasis. Reduction of intestinal Pi absorption with the use of Pi binders is currently the primary treatment for Pi retention in patients with ESRD. The use of large doses of calcium-containing Pi binders along with calcitriol administration may contribute to over-suppression of parathyroid hormone secretion and adynamic bone disease as well as to a high incidence of vascular calcifications. When used in patients with impaired renal function, aluminium salts were found to accumulate in bone and other tissues, resulting in osteomalacia and encephalopathy.Sevelamer, an aluminium- and calcium-free Pi binder can reduce serum phosphorus concentration and is associated with a significantly lower incidence of hypercalcaemia, while maintaining the ability to suppress parathyroid hormone production. An additional benefit of sevelamer is its ability to lower low density lipoprotein-cholesterol and total cholesterol levels. Sevelamer attenuates the progression of vascular calcifications in haemodialysis patients, which may lead to lower mortality. The use of sevelamer in non-dialysed patients might aggravate metabolic acidosis, common in these patients. Several other calcium-free Pi binders are in development. Lanthanum carbonate has shown significant promise in clinical trials in ESRD patients. Magnesium salts do not offer a significant advantage over currently available Pi binders. Their use is restricted to patients receiving dialysis since excess magnesium must be removed by dialysis. Iron-based compounds have shown variable efficacy in short-term clinical trials in small numbers of haemodialysis patients. Mixed metal hydroxyl carbonate compounds have shown efficacy in animals but have not been studied in humans. Major safety issues include absorption of the metal component with possible tissue accumulation and toxicity.     

The role of sevelamer in achieving the kidney disease outcomes quality initiative (K/DOQI) guidelines for hyperphosphatemia

BACKGROUND: End-stage renal disease (ESRD) is a chronic health care problem associated with multiple co-morbidities and escalating costs. Disregulation of mineral metabolism (principally hyperphosphatemia and hypercalcemia) contributes to substantial morbidity and mortality. Accordingly, new and more-aggressive Kidney Disease Outcomes Quality Initiative (K/DOQI) Guidelines from the National Kidney Foundation promote lower serum phosphorus (3.5-5.5 mg/dL), lower calcium (8.4-9.5 mg/dL), and lower calcium-phosphorus product (< 55 mg(2)/dL(2)) targets. REVIEW FINDINGS: Traditional calcium-based and metal-based phosphate binders are effective but are associated with side effects and toxicity that limit their use. Achieving rigorous K/DOQI goals demands higher therapeutic doses of phosphate binders and may require more-aggressive use of calcium-free and metal-free phosphate binders. Sevelamer hydrochloride is a calcium- and metal-free polymer that binds phosphate effectively without contributing to calcium load or metal accumulation. In the Treat-to-Goal trial, sevelamer-treated dialysis patients had less progression of coronary and aortic calcification than patients treated with calcium-based binders. This offers the potential promise of reducing cardiovascular morbidity and mortality. The 800-mg tablet (Renagel) increases the daily sevelamer dose while reducing the number of tablets required per meal. Nine of the 800-mg tablets per day (3 x 800-mg tablets tid with meals) of sevelamer monotherapy have been shown to achieve K/DOQI serum phosphorus and calcium-phosphorus product targets. CONCLUSION: In summary, this review of the current evidence-base concludes that the new, more-aggressive, K/DOQI goals limit the use of metal-based and calcium-based phosphate binders. Sevelamer offers the advantages of lowering serum phosphorus without the risks of calcium or metal accumulation - and offers the promise of slowing the progression of vascular calcification and potentially reducing the morbidity and mortality of hemodialysis patients.     

An economic evaluation of sevelamer in patients new to dialysis

ABSTRACT

Objective: The overall objective of this study was to estimate the costs and outcomes associated with treatment with sevelamer for hyperphosphataemia compared with calcium-based binders.

Methods: Using published data on mortality and hospitalisation rates, a Markov model was developed to predict health outcomes and associated costs for the treatment of hyperphosphataemia using either sevelamer or calcium binders in chronic kidney disease patients who had recently started haemodialysis. Patient outcomes were modelled for 5 years, and incremental cost-effective ratios (ICERs) were calculated for sevelamer relative to calcium carbonate and calcium acetate binders. The perspective adopted was that of the UK National Health Service.

Results: The total 5-year discounted treatment cost for patients treated with sevelamer is £24?216, while for the calcium carbonate group total cost was £17?695. This is an incremental cost of £6521 per sevelamer-treated patient over 5 years. Patients receiving sevelamer can be expected to experience 2.70 quality-adjusted life years (QALYs) compared to 2.46 for those treated with calcium carbonate (i.e. an incremental gain of 0.24 QALYs). This results in an incremental cost per QALY of £27?120 and an incremental cost per life year gained of £15?508. Results were similar with calcium acetate.

Conclusion: Together with the unique morbidity and mortality benefits, this study suggests that treatment with sevelamer confers clinical benefits with a modest investment of additional economic resources.     

The role of sevelamer in achieving the kidney disease outcomes quality initiative (K/DOQI) guidelines for hyperphosphatemia

SUMMARY

Background: End-stage renal disease (ESRD) is a chronic health care problem associated with multiple co-morbidities and escalating costs. Disregulation of mineral metabolism (principally hyperphosphatemia and hypercalcemia) contributes to substantial morbidity and mortality. Accordingly, new and more-aggressive Kidney Disease Outcomes Quality Initiative (K/DOQI) Guidelines from the National Kidney Foundation promote lower serum phosphorus (3.5–5.5?mg/dL), lower calcium (8.4–9.5?mg/dL), and lower calcium-phosphorus product (< 55?mg²/dL²) targets.

Review findings: Traditional calcium-based and metal-based phosphate binders are effective but are associated with side effects and toxicity that limit their use. Achieving rigorous K/DOQI goals demands higher therapeutic doses of phosphate binders and may require more-aggressive use of calcium-free and metal-free phosphate binders. Sevelamer hydrochloride is a calcium- and metal-free polymer that binds phosphate effectively without contributing to calcium load or metal accumulation. In the Treat-to-Goal trial, sevelamer-treated dialysis patients had less progression of coronary and aortic calcification than patients treated with calcium-based binders. This offers the potential promise of reducing cardiovascular morbidity and mortality. The 800-mg tablet (Renagel*) increases the daily sevelamer dose while reducing the number of tablets required per meal. Nine of the 800-mg tablets per day (3 × 800-mg tablets tid with meals) of sevelamer monotherapy have been shown to achieve K/DOQI serum phosphorus and calcium-phosphorus product targets.

Conclusion: In summary, this review of the current evidence-base concludes that the new, more-aggressive, K/DOQI goals limit the use of metal-based and calcium-based phosphate binders. Sevelamer offers the advantages of lowering serum phosphorus without the risks of calcium or metal accumulation – and offers the promise of slowing the progression of vascular calcification and potentially reducing the morbidity and mortality of hemodialysis patients.     

A comparative review of the efficacy and safety of established phosphate binders: calcium,sevelamer, and lanthanum carbonate*

ABSTRACT

Background: Obstacles to successful management of hyperphosphatemia in chronic kidney disease include inadequate control of dietary phosphate and non-compliance with phosphate-binder therapy. Three major classes of phosphate binders include calcium-based binders, sevelamer HCl, and lanthanum carbonate.

Scope: A literature search was performed using MEDLINE and EMBASE databases to identify clinical trials from January 1966 to May 2007 comparing classes of phosphate binders with regard to efficacy, safety, compliance, or pharmacoeconomics. Search terms included lanthanum AND sevelamer, lanthanum AND calcium, and sevelamer AND calcium. A total of 1372 articles were identified in the search, with 125 review articles and clinical trials of interest identified.

Findings: Calcium-based binders are effective, but their potential to contribute to total body calcium overload and vascular calcification is an important long-term clinical concern. Sevelamer HCl is effective in reducing serum phosphate, has no systemic absorption, and does not increase total body calcium load. However, sevelamer HCl binds bile acids, is not an efficient phosphate binder in an acidic environment, and contributes to metabolic acidosis. Lanthanum carbonate is a potent and selective phosphate binder that retains high affinity for phosphate over a wide pH range, does not bind bile acids or contribute to metabolic acidosis, and has the potential to reduce pill burden and increase patient compliance compared with other phosphate binders.

Conclusions: All three classes of phosphate binders are effective at reducing serum phosphate levels. Lanthanum carbonate may result in increased adherence by decreasing the pill burden.     

Effect of phosphate binders on supplemental iron absorption in healthy subjects

A single-dose, prospective, randomized, four-treatment, four-period crossover study was conducted to determine the acute effect of therapeutically equivalent doses of three commonly used phosphate binders on oral iron absorption. Twenty-three healthy subjects received 65 mg of elemental iron alone and with each phosphate binder (calcium carbonate 3000 mg, calcium acetate 2668 mg, or sevelamer HCl 2821 mg). Area under the change in plasma iron concentration-time curve over 6 hours postdosing was measured. ANOVA was used to assess the statistical significance of differences in iron absorption among the treatments. The relative bioavailability of iron administered with each phosphate binder compared to iron administered alone was estimated. The relative iron bioavailabilities (95% confidence intervals) for the calcium carbonate, calcium acetate, and sevelamer HCI treatments were 0.81 (0.70, 0.94), 0.73 (0.63, 0.85), and 0.90 (0.78, 1.05), respectively. Thus, single doses of both calcium-based phosphate binders significantly reduced single-dose iron absorption, while sevelamer HCl did not.     

Emerging drugs for hyperphosphatemia

Cardiovascular mortality is the leading cause of death in the uremic patient. Hyperphosphatemia is considered an independent risk factor associated with cardiovascular morbidity and mortality in dialysis patients. As phosphate control is not efficient with diet or dialysis, phosphate binders are commonly prescribed in patients with chronic renal failure. Aluminum salts, the first phosphate binders, even if effective, have several side effects due to their deposition in CNS, bone and hematopoietic cells. Calcium-containing phosphate binders, used in the last 15 years, increase total body calcium load and may exacerbate metastatic calcification, thus, increasing the risk of cardiovascular mortality. Recently two new compounds non-aluminum and non-calcium phosphate binders, sevelamer hydrochloride and lanthanum carbonate, have been introduced. Sevelamer, besides the effect on phosphate, has been associated with reduction of coronary and aortic calcification and with other pleiotropic effects especially on lipid metabolism. Lanthanum carbonate has similar phosphate control to calcium-based binders with less incidence of hypercalcemia but long-term clinical studies are needed for testing long-term exposure. Recently the authors found in dialysis patients, that salivary phosphorus correlated with serum phosphorus. Therefore, they supposed that the use of salivary phosphate binders could reduce its absorption and represent a chance for reducing the serum phosphate concentration in uremic patients.     

新型磷结合剂碳酸司维拉姆临床应用

碳酸司维拉姆作为一种不吸收的非钙、非金属的磷结合剂,临床用于控制正在接受透析治疗的慢性肾脏病成人患者的高磷血症,目前已在40多国上市并广泛使用。本文通过对碳酸司维拉姆进行文献检索,并对其作用机制、药效学、药动学、临床评价、适应证及药品相关不良反应等进行综述。     

Pharmacological and clinical trial data on a novel phosphate-binding polymer (sevelamer hydrochloride), a medicine for hyperphosphatemia in hemodialysis patients

Hyperphosphatemia is one of the major complications of hemodialysis patients and plays a key role in the pathogenesis of cardiovascular calcification and secondary hyperparathyroidism. Dietary phosphate restriction and removal of phosphate by dialysis are insufficient to control hyperphosphatemia. Therefore, almost all patients undergoing hemodialysis should take oral phosphate binders. Sevelamer hydrochloride (sevelamer) is a novel phosphate-binding polymer that contains neither aluminum nor calcium, and it is not absorbed from the gastrointestinal tract. In rat models with progressive chronic renal insufficiency, in addition to lowering effects on serum levels of phosphorus, calcium x phosphorus product, and parathyroid hormone, dietary treatment of sevelamer can prevent parathyroid hyperplasia, vascular calcification, high turnover bone lesion, and renal functional deterioration. In clinical studies with hemodialysis patients, sevelamer lowers serum phosphorus and calcium x phosphorus product without any incidence of hypercalcemia. Switching calcium-containing phosphate binders to sevelamer can decrease the percentage of hypoparathyroidism and hyperparathyroidism by negative calcium balance and increased dosage of vitamin D, respectively. Sevelamer also decreases serum low-density lipoprotein cholesterol levels by its bile acid-binding capacity. A long-term clinical study has demonstrated that the progression of coronary and aortic calcification in hemodialysis patients is attenuated by sevelamer. Thus, sevelamer offers the promise of impacting cardiac calcification and thereby reducing morbidity and mortality of hemodialysis patients.     

Emerging drugs for hyperphosphatemia

Cardiovascular mortality is the leading cause of death in the uremic patient. Hyperphosphatemia is considered an independent risk factor associated with cardiovascular morbidity and mortality in dialysis patients. As phosphate control is not efficient with diet or dialysis, phosphate binders are commonly prescribed in patients with chronic renal failure. Aluminum salts, the first phosphate binders, even if effective, have several side effects due to their deposition in CNS, bone and hematopoietic cells. Calcium-containing phosphate binders, used in the last 15 years, increase total body calcium load and may exacerbate metastatic calcification, thus, increasing the risk of cardiovascular mortality. Recently two new compounds non-aluminum and non-calcium phosphate binders, sevelamer hydrochloride and lanthanum carbonate, have been introduced. Sevelamer, besides the effect on phosphate, has been associated with reduction of coronary and aortic calcification and with other pleiotropic effects especially on lipid metabolism. Lanthanum carbonate has similar phosphate control to calcium-based binders with less incidence of hypercalcemia but long-term clinical studies are needed for testing long-term exposure. Recently the authors found in dialysis patients, that salivary phosphorus correlated with serum phosphorus. Therefore, they supposed that the use of salivary phosphate binders could reduce its absorption and represent a chance for reducing the serum phosphate concentration in uremic patients.     

Sevelamer as a phosphate binder in adult hemodialysis patients: an evidence-based review of its therapeutic value

INTRODUCTION: Patients on hemodialysis require phosphate binders to reduce dietary phosphate absorption and control serum phosphate. The standard therapy, calcium salts, can be associated with elevated serum calcium (hypercalcemia). Concern has been raised that hypercalcemia, especially combined with elevated serum phosphate, may be associated with arterial calcification, and this may contribute to increased risk of cardiovascular mortality and morbidity. Sevelamer is a nonmetal, nonabsorbed phosphate binder. AIMS: This review assesses the evidence for the therapeutic value of sevelamer as a phosphate binder in adult hemodialysis patients. EVIDENCE REVIEW: Strong evidence shows that sevelamer is as effective as calcium salts in controlling serum phosphate and calcium-phosphate product, has less risk of inducing hypercalcemia and is more effective at lowering lipid levels. Some evidence indicates that sevelamer reduces arterial calcification progression and loss of bone mineral density, but it may be more likely to induce metabolic acidosis, compared with calcium salts. Sevelamer-containing regimens may improve calcific uremic arteriolopathy, although the evidence is weak. Evidence is divided on whether the incidence of gastrointestinal adverse events with sevelamer is similar to or higher than that with calcium salts. Retrospective and modeling studies suggest lower cardiovascular morbidity and mortality with sevelamer than with calcium salts, with incremental cost-effectiveness of $US1100-2200 per life-year gained. Further direct evidence is needed on mortality, quality of life, and cost-effectiveness. PLACE IN THERAPY: Sevelamer is effective in controlling serum phosphate and lowering lipid levels in hemodialysis patients without inducing hypercalcemia, and may have beneficial effects on arterial calcification.     

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.     

Protein-Bound Uremic Toxins Lowering Effect of Sevelamer in Pre-Dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial

P-cresyl sulfate and indoxyl sulfate are strongly associated with cardiovascular events and all-cause mortality in chronic kidney disease (CKD). This randomized controlled trial was conducted to compare the effects between sevelamer and calcium carbonate on protein-bound uremic toxins in pre-dialysis CKD patients with hyperphosphatemia. Forty pre-dialysis CKD patients with persistent hyperphosphatemia were randomly assigned to receive either 2400 mg of sevelamer daily or 1500 mg of calcium carbonate daily for 24 weeks. A significant decrease of total serum p-cresyl sulfate was observed in sevelamer therapy compared to calcium carbonate therapy (mean difference between two groups −5.61 mg/L; 95% CI −11.01 to −0.27 mg/L; p = 0.04). There was no significant difference in serum indoxyl sulfate levels (p = 0.36). Sevelamer had effects in terms of lowering fibroblast growth factor 23 (p = 0.01) and low-density lipoprotein cholesterol levels (p = 0.04). Sevelamer showed benefits in terms of retarding CKD progression. Changes in vascular stiffness were not found in this study.     

Compounds in development to combat hyperphosphataemia

Hyperphosphataemia in haemodialysis patients is associated with secondary hyperparathyroidism and more importantly with an increased cardiovascular mortality in dialysed patients. Removal of phosphate during dialysis is less than net intestinal uptake. This imbalance results in a positive phosphate balance. To control serum phosphate concentration oral phosphate binders have to be taken to reduce net intestinal uptake. The use of classical phosphate binders such as calcium carbonate, calcium acetate and aluminium-containing phosphate binders is limited by their side effects. Hypercalcaemia aggravates vascular calcification and cardiovascular risk. Aluminium intoxication causes aluminium osteopathy, anaemia and encephalopathy. Therefore, the development of calcium- and aluminium free phosphate binders has become a challenge to clinical nephrology. Polyallylamine hydrochloride (sevelamer) is one of the new alternative compounds which has been shown to effectively bind phosphate in dialysis patients. A promising approach in the development of alternative phophate binders are trivalent-iron (Fe(III)) containing phosphate binders. They were not only successfully tested in experimental animals but have also been shown to reduce urinary phosphate excretion and serum phosphate concentrations in patients with preterminal failure and those on maintenance haemodialysis. This review outlines the experimental and clinical data on Fe-III based phosphate binders providing evidence that they will be as effective and safe as phosphate binders without the major side effects of classical phosphate-binding compounds.     

2种不同磷结合剂治疗维持性血液透析患者高磷血症的对比研究

目的观察对比2种不同的磷结合剂对维持性血液透析患者高磷血症的治疗效果。方法选取肾内科维持性血液透析并高磷血症患者64例,随机分为观察组和对照组各32例,对照组应用碳酸钙治疗,观察组应用盐酸司维拉姆进行治疗。观察两组患者的治疗有效率及血液生化指标中血清高密度脂蛋白、血磷、血清钙磷乘积的变化情况及不良反应。结果治疗后,观察组和对照组患者血磷、血清钙磷的乘积均较治疗前显著下降,差异具有统计学意义（P〈0.05）;观察组这两项指标下降更为明显,与对照组相比差异具有统计学意义（P〈0.05）;观察组的治疗有效率显著高于对照组（P〈0.05）;观察组患者血清高密度脂蛋白较治疗前显著上升（P〈0.05）;观察组高钙血症发生率低于对照组,但差异无统计学意义（P〉0.05）。结论盐酸司维拉姆比碳酸钙对维持性血液透析患者高磷血症具有更好的短期疗效。     

Hyperphosphatemia and phosphate binders.

PURPOSE: The pathophysiology of hyperphosphatemia associated with end-stage renal disease and treatment with phosphate binders are discussed. SUMMARY: Phosphorus is an essential element necessary for the normal function of the human body, required for skeletal construction and synthesis of DNA, proteins, and adenosine triphosphate. In healthy individuals, serum phosphorus concentrations are maintained between 2.5 and 4.5 mg/dL through diet and renal excretion. In renal insufficiency, phosphorus excretion declines and hyperphosphatemia develops. The body's compensation mechanisms cause secondary hyperparathyroidism and renal osteodystrophy. Phosphate binders provide an effective means for managing serum phosphate. Commercially available phosphate binders include calcium carbonate, calcium acetate, sevelamer, lanthanum, and, rarely, aluminum hydroxide. Because of aluminum's known toxicities, aluminum-based phosphate binders have a limited place in therapy. Calcium carbonate's benefits are seen over a narrow gastric pH range, thereby limiting the drug's utility. Calcium acetate is effective over a wide pH range. Other phosphate binders, including sevelamer hydrochloride and lanthanum carbonate, have recently entered the market, but their use remains controversial. CONCLUSION: If left untreated, hyperphosphatemia can result in secondary hyperparathyroidism, renal osteodystrophy, and metastatic calcification of blood vessels and soft tissue. The treatment of hyperphosphatemia in patients with chronic renal failure includes dialysis, dietary phosphorus restrictions, phosphate-binding medications, and vitamin D analogs. Selection of phosphate binders should be based on patient characteristics, including serum phosphate, serum calcium, and intact parathyroid hormone concentrations, and patient tolerability.     

Lanthanum carbonate

Controlling hyperphosphatemia in patients with chronic renal failure on renal dialysis is a major problem. None of the available calcium- or aluminum-based phosphate binders match the requirements for an ideal agent, each having its own limitations. The introduction of sevelamer hydrochloride represented a step change in management. Lanthanum carbonate is an alternative nonaluminium, noncalcium phosphate binder. 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, but despite the large numbers of patients included in clinical trials, experience with long-term dosing is limited and, as with every new drug used in this type of clinical setting, patients should be carefully monitored as experience with the drug increases. Lanthanum carbonate binds phosphate effectively across the physiological pH range of the upper gastrointestinal tract, and has no detrimental effect on calcium, vitamin D or parathyroid hormone metabolism. From the extensive trial data it seems that lanthanum carbonate is an effective and practical phosphate binder. Lanthanum carbonate and sevelamer are two new oral phosphate binding agents that with others currently in preclinical trials, such as stabilized polynuclear iron idroxide, could well represent a significant breakthrough in the management of hyperphosphatemia in patients with chronic renal failure in whom dietary phosphate restriction and cheaper oral phosphate binding agents prove unsatisfactory. Comparative trials and enhanced clinical experience are needed before the exact place of these competing and complementary therapies can be properly identified in patient management.     

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.