Hyperphosphatemia In End-stage Renal Disease Research Articles

The Influence of Sevelamer Hydrochloride and Calcium Carbonate on Markers of Inflammation and Oxidative Stress in Hemodialysis at Six Months of Follow-Up.

Patients with end-stage renal disease (ESRD) present alterations in mineral and bone metabolism. Hyperphosphatemia in ESRD is considered an independent risk factor for cardiovascular disease (CVD), increasing morbidity, and mortality. Sevelamer hydrochloride is a calcium-free, non-absorbable phosphate-chelating polymer. Calcium carbonate chelator is helpful in controlling serum phosphate levels. There is insufficient information on the influence of sevelamer hydrochloride and calcium carbonate on the behavior of oxidative stress (OS) markers and inflammation in patients on hemodialysis (HD). A randomized open clinical trial was carried out on patients to evaluate sevelamer hydrochloride and calcium carbonate influence at 6 months of study follow-up. Levels of oxidants (LPO, NO, and 8-isoprostanes), antioxidants (SOD and TAC), oxidative DNA damage (8-OHdG and hOGG1), pro-inflammatory cytokines (IL-6 and TNF-α), and inflammation markers (ferritin and C-reactive protein) were measured with colorimetric and ELISA methods. We found a significant increase in oxidants LPO and NO, and antioxidants SOD and TAC, and downregulation of IL-6 and TNF-α. Ferritin decrease at 6 months follow-up in the sevelamer hydrochloride group. Increase in C-reactive protein was found in the group of patients treated with calcium carbonate. In conclusion, we found an oxidative state imbalance with increase in LPO and NO oxidants. The activity of the antioxidant enzymes (SOD and TAC) was also found to increase, suggesting a compensatory effect in the face of increase in oxidants. The same phenomenon was observed with increase in the oxidative damage marker to DNA and the increase in the DNA repair enzyme, suggesting a compensatory effect. Pro-inflammatory cytokines were predominantly downregulated by TNF-α in the group that ingested sevelamer hydrochloride in the final determination at 6 months of follow-up. Serum ferritin levels decreased significantly at the end of follow-up in patients on HD in the sevelamer hydrochloride group. The management of hyperphosphatemia with sevelamer hydrochloride appears to have obvious anti-inflammatory and antioxidant benefits.

The Novel Phosphate and Bile Acid Sequestrant Polymer SAR442357 Delays Disease Progression in a Rat Model of Diabetic Nephropathy.

As a gut-restricted, nonabsorbed therapy, polymeric bile acid sequestrants (BAS) play an important role in managing hyperlipidemia and hyperglycemia. Similarly, nonabsorbable sequestrants of dietary phosphate have been used for the management of hyperphosphatemia in end-stage renal disease. To evaluate the potential utility of such polymer sequestrants to treat type 2 diabetes (T2D) and its associated renal and cardiovascular complications, we synthesized a novel polymeric sequestrant, SAR442357, possessing optimized bile acid (BA) and phosphate sequestration characteristics. Long-term treatment of T2D obese cZucker fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1) with SAR442357 resulted in enhanced sequestration of BAs and phosphate in the gut, improved glycemic control, lowering of serum cholesterol, and attenuation of diabetic kidney disease (DKD) progression. In comparison, colesevelam, a BAS with poor phosphate binding properties, did not prevent DKD progression, whereas losartan, an angiotensin II receptor blocker that is widely used to treat DKD, showed no effect on hyperglycemia. Analysis of hepatic gene expression levels of the animals treated with SAR442357 revealed upregulation of genes responsible for the biosynthesis of cholesterol and BAs, providing clear evidence of target engagement and mode of action of the new sequestrant. Additional hepatic gene expression pathway changes were indicative of an interruption of the enterohepatic BA cycle. Histopathological analysis of ZSF1 rat kidneys treated with SAR442357 further supported its nephroprotective properties. Collectively, these findings reveal the pharmacological benefit of simultaneous sequestration of BAs and phosphate in treating T2D and its associated comorbidities and cardiovascular complications. SIGNIFICANCE STATEMENT: A new nonabsorbed polymeric sequestrant with optimum phosphate and bile salt sequestration properties was developed as a treatment option for DKD. The new polymeric sequestrant offered combined pharmacological benefits including glucose regulation, lipid lowering, and attenuation of DKD progression in a single therapeutic agent.

Use of Phosphate Binders in End-Stage Renal Disease: An Experience From a Secondary Care Hospital in United Arab Emirates.

ABSTRACTObjective:Hyperphosphatemia in end-stage renal disease (ESRD) is associated with many serious patient-level consequences including cardiovascular events and mortality. The purpose of this study was to investigate the use of phosphate binders in ESRD patients on maintenance hemodialysis.Materials and Methods:The study was a prospective observational cohort study including adult ESRD patients undergoing hemodialysis at a secondary hospital in United Arab Emirates. Patient characteristics were compared as per type of phosphate binder used. Bivariate and multivariate multinomial logistic regression analyses were carried out to determine variables that were independently associated with use of different phosphate binders.Results:Phosphate binders used at our study site were sevelamer, calcium carbonate, and a combination of sevelamer and calcium carbonate. Bivariate multinomial logistic regression analysis revealed that serum phosphorous (odds ratio [OR]: 0.14, 95% confidence interval [CI]: 0.04–1.09, P = 0.047; OR: 0.10, 95% CI: 0.03–0.89, P = 0.042), calcium (OR: 0.11, 95% CI: 0.02–0.86, P = 0.041; OR: 0.22, 95% CI: 0.01–0.96, P = 0.012), and calcium–phosphorous product (OR: 0.20, 95% CI: 0.06–0.64, P = 0.008; OR: 0.16, 95% CI: 0.05–0.54, P = 0.003) levels were significantly lower in patients on sevelamer per se as well as in patients on combination therapy, respectively when compared to calcium carbonate per se. Multivariate multinomial logistic regression analysis revealed that in sevelamer and combination groups, cardiovascular diseases (OR: 0.12, 95% CI: 0.02–0.65, P = 0.022; OR: 0.10, 95% CI: 0.01–0.88, P = 0.038) were significantly lesser compared to calcium carbonate group after being adjusted for other variables in the model.Conclusion:We observed that hyperphosphatemia and related events in our study population were better controlled by sevelamer per se and combination therapy than calcium carbonate per se. Further large scale, multicenter studies are required to confirm and establish these findings.

NPT-IIb Inhibition Does Not Improve Hyperphosphatemia in CKD

IntroductionSerum phosphate levels are insufficiently controlled in many patients with end-stage renal disease (ESRD), and novel therapeutic strategies are needed. Blocking intestinal phosphate absorption mediated by sodium-dependent phosphate co-transporter type 2b (NPT-IIb) holds promise; thus, we evaluated the efficacy, safety, tolerability, and pharmacokinetics of the novel and specific small molecule NPT-IIb inhibitor ASP3325 for the first time in humans.MethodsWe conducted a randomized, double-blind, placebo-controlled, phase 1a single (n = 88) and multiple (n = 36) ascending dose study in healthy subjects, and a randomized, open-label, uncontrolled, phase 1b study in hyperphosphatemic ESRD patients on hemodialysis (single oral dose, n = 5; multiple oral doses, n = 17). Primary efficacy measures were urinary phosphate and fecal phosphorous excretion (healthy subjects) and serum phosphate level (ESRD patients).ResultsNo time- or dose-dependent changes in urinary phosphate or fecal phosphorous excretion were observed following single/multiple ASP3325 doses for 7 days in healthy subjects. In ESRD patients, ASP3325 administered 3 times daily for 2 weeks before or after a meal did not reduce serum phosphate levels. ASP3325 was safe and well tolerated in both populations.ConclusionNPT-IIb inhibition with ASP3325 was not effective in reducing serum phosphate levels in ESRD patients. The relevance of NPT-IIb in humans and feasibility of oral NPT-IIb inhibitors for treatment of hyperphosphatemia in ESRD remain uncertain.

Optimal management of hyperphosphatemia in end-stage renal disease: an Indian perspective.

There has been an exponential increase in the incidence of diabetes and hypertension in India in the last few decades, with a proportional increase in chronic kidney disease (CKD). Preventive health care and maintenance of asymptomatic chronic disease such as CKD are often neglected by patients until they become symptomatic with fluid retention and uremia. Management of hyperphosphatemia in CKD remains one of the challenges of nephrology in India for this reason, as it is almost completely asymptomatic but contributes to renal osteodystrophy, metastatic vascular calcification, and acceleration of cardiovascular disease. Lack of understanding of the dangers of asymptomatic hyperphosphatemia, the huge pill burden of phosphate binders, difficulty with dietary and dialysis compliance, and most importantly, the added expense of the drugs places additional road blocks in the treatment of hyperphosphatemia at a population level in developing countries like India. In this review we seek to address the contribution of hyperphosphatemia to adverse outcomes and discuss economic, cultural, and societal factors unique to the management of phosphate levels in Indian patients with advanced CKD.

Understanding the Associations Between Modifying Factors, Individual Health Beliefs, and Hemodialysis Patients' Adherence to a Low-Phosphorus Diet

Hyperphosphatemia in end-stage renal disease is associated with significant morbidity and mortality. Because phosphorus is not effectively dialyzed, dietary adherence remains a significant problem. Previous studies have examined the health belief model, but none have looked at stages of change and dietary adherence in patients undergoing hemodialysis (HD). Cross-sectional survey. Three dialysis centers in Columbus, Ohio, between August 2012 and March2013. English-speaking patients age 18 or older on HD without dementia or developmental delay. None. Associations between dietary adherence based on the Precaution Adoption Process Model (stages of change) and serum phosphorus levels via a conceptual model incorporating modifying factors and individual health beliefs. Ninety-five patients completed the survey; 59 (62%) endorsed adherence to a low-phosphorus diet and 32 (34%) had phosphorus values ≤5.5mg/dL. Modifying factors associated with diet adherence included nonminority status odds ratio (OR), 95%CI 8.99 (1.08-74.60), greater level of education OR 18.23 (1.62-205.00), better quality of life OR 9.28 (1.35-63.71), and time on dialysis OR 1.04 (1.01-1.07). Individual health beliefs associated with diet adherence included perceived benefits OR 3.18 (1.47-6.88) and self-efficacy OR 1.22 (1.09-1.38). Modifying factors associated with phosphorus control included: age OR 0.94 (0.90-0.99), minority status OR 0.11 (0.02-0.68), greater level of education OR 6.60 (1.41-31.04), knowledge about chronic kidney disease OR 1.48 (1.03-2.13), and time on dialysis OR 0.98 (0.96-0.99). Individual health beliefs associated with phosphorus control included self-efficacy OR 1.08 (1.01-1.16). HD clinicians and educators may obtain better results with dietary adherence and phosphorus control if they focus not only toward disease and dietary education but also on understanding modifying factors and individual health beliefs. Assessing where the patient is with regard to stages of change may assist health care providers in better matching interventions that build patients' self-efficacy.

Use of Nicotinamide to Treat Hyperphosphatemia in Dialysis Patients

Hyperphosphatemia in chronic kidney disease (CKD) has been associated with elevated cardiovascular morbidity and mortality. Serum phosphate control remains a cornerstone of the clinical management of patients with CKD, in order to both attenuate the progression of secondary hyperparathyroidism or bone disease and (possibly) reduce the risk of vascular calcification. Despite technical improvements in dialysis and the use of dietary restrictions, drug therapy is often required to control phosphate levels in patients with end-stage renal disease (ESRD). Currently available medications for hyperphosphatemia in ESRD are very expensive and not always well tolerated. The discovery and development of new drugs in this indication is therefore a priority for both medical and health-economic reasons. Nicotinamide (an amide derivative of the water-soluble vitamin B3) is a potentially interesting alternative to phosphate binders. In vitro and in vivo data show that nicotinamide reduces hyperphosphatemia by inhibiting sodium-dependent phosphate co-transport in the renal proximal tubule and in the intestine. Accordingly, targeting the sodium-dependent phosphate co-transporter 2b by using nicotinamide as an alternative or adjunct to classical phosphate binders may be a therapeutic option for modulating serum phosphate in CKD. Several recent clinical studies have explored the potential value of nicotinamide in phosphate control (as well as its effects on lipid levels) in dialysis patients. However, we consider that more data on pharmacodynamics, pharmacokinetics and safety are needed before this compound can be recommended as a treatment for hyperphosphatemia in ESRD patients.

Cost-Effectiveness of Lanthanum Carbonate versus Sevelamer Hydrochloride for the Treatment of Hyperphosphatemia in Patients with End-Stage Renal Disease: A US Payer Perspective

Objective To assess the cost-effectiveness of lanthanum carbonate (LC) versus sevelamer hydrochloride (SH) as a treatment for hyperphosphatemia in end-stage renal disease (ESRD) patients. Methods A Markov model was developed to estimate health outcomes; quality-adjusted life years (QALYs) and life-years saved (LYS), as well as associated costs. The model incorporated patient-level data from a randomized head-to-head crossover study that compared the reduction of serum phosphorus using LC and SH for 4 weeks each. The model included patients previously treated with calcium-based binders. Both the intent-to-treat (ITT) population and the cohort of patients who completed treatment in both periods of the study (i.e., completer population) were assessed. The baseline risks of cardiovascular disease (CVD), all-cause mortalities for CVD, and non-CVD patients were derived from a large US renal database. Patient outcomes were modeled for 10 years, and incremental cost-effectiveness ratios (ICERs) were calculated for LC relative to SH. Deterministic and probabilistic sensitivity analyses (PSA) were performed to test the robustness of the base-case model. Results For the ITT population, the ICERs of LC versus SH were $24,724/QALY and $15,053/LYS, respectively (in US dollars). When the completer population was considered, the ICERs of LC versus SH were $15,285/QALY and $9,337/LYS ( Table 2), respectively. The PSA indicated 61.9% and 85.8% probabilities for ITT and completer populations of LC being cost-effective at the $50,000/QALY willingness-to-pay threshold, respectively. Conclusion LC is a cost-effective strategy compared with SH in the treatment of ESRD patients with hyperphosphatemia who were previously treated with calcium-based binders. Sensitivity analyses demonstrated the robustness of the pharmacoeconomic model.

The Control of Hyperphosphatemia in Chronic Kidney Disease: Which Phosphate Binder?

Hyperphosphatemia is currently regarded as a key mortality risk predictor in late CKD stages and especially in patients on dialysis. Fortunately, the armatorium to effectively treat hyperphosphatemia in end-stage renal disease has grown in recent years, and we gained an improved understanding of potential benefits and harms of specific compounds. Most interestingly, novel insights into the pathophysiology of calcium and phosphate handling, especially, the discovery of the phosphatonin FGF23, suggest a more complex assessment of phosphate balance especially in predialysis stages is warranted. This assessment should probably include measurements of fractional phosphate excretion and phosphatonin levels to objectively judge and effectively correct phosphate overload, however, clinical data on calcium and phosphate metabolism in CKD stages 3 - 4 are still scarce. This overview will both discuss aspects of pathophysiology of phosphate regulation and current and future clinical treatement approaches.

Phosphate Salivary Secretion in Hemodialysis Patients: Implications for the Treatment of Hyperphosphatemia

Background/Aims: Hyperphosphatemia is recognized as contributing to the increased risk of cardiac death in end-stage renal disease (ESRD) and hemodialysis (HD) patients. Currently available pharmacologic treatment for hyperphosphatemia is based on phosphate binders but, despite treatment, only half of the patients fall within the range for serum phosphorus of the K/DOQI guidelines. Therefore, there is a need to identify other therapeutic approaches in order to reduce serum phosphate. Salivary fluid contains phosphate which, if related to the daily salivary secretion (1,000–1,880 ml), may raise interest in order to identify further additive approaches to phosphorus removal in uremic patients, while data about salivary phosphate secretion in ESRD patients are controversial. Methods: This study evaluates salivary phosphate secretion in 68 HD patients compared with 30 healthy subjects. Saxon’s test confirmed normal salivary function in patients and controls. Salivary calcium and serum phosphate, calcium and PTH were also measured. Results: HD patients had significantly higher salivary phosphorus levels compared with healthy controls: 30.35 (26.5–34.6) vs. 12.1 (10.58–14.73) mg/dl (p < 0.0001), and this significantly correlated (p < 0.0001) with serum phosphorus. Multiple regression analysis confirmed serum phosphorus as the only predictor (p < 0.0001) of salivary phosphorus. Conclusions: Given the functional secretive similarity between salivary glands and the kidneys, this increased salivary phosphate secretion might be interpreted as being compensatory in the presence of renal failure. Absorption of the increased salivary phosphate secretion, however, may worsen hyperphosphatemia; therefore, the binding of salivary phosphate might be considered as a further therapeutic approach to hyperphosphatemia in ESRD.

The Cost-Effectiveness of Lanthanum Carbonate in the Treatment of Hyperphosphatemia in Patients with End-Stage Renal Disease

Objectives To assess the cost-effectiveness of lanthanum carbonate (LC) as a second-line therapy for hyperphosphatemia in end-stage renal disease (ESRD) patients not achieving target phosphorus levels. Methods A cohort of ESRD patients not adequately maintained on calcium carbonate (CC) and three subgroups of patients with baseline phosphorus levels of 5.6 to 6.5 mg/dl, 6.6 to 7.8 mg/dl, and more than 7.9 mg/dl were modeled. The following policy options were considered: continued CC (Policy 1); LC trial—if successful continue LC, if unsuccessful switch to CC (Policy 2). The survival benefit of using second-line LC to improve phosphorus control has been extrapolated from the relationship between hyperphosphatemia and mortality. Lifetime UK National Health Service drug and monitoring costs, expected survival, and quality-adjusted life-years (QALYs) were examined (discounting at 3.5% per annum). Results Policy 2 had a cost-effectiveness ratio (cost/QALY) of £25,033 relative to Policy 1. The results show it is particularly cost-effective to treat patients with phosphorus levels above 6.6 mg/dl. The outcomes did not vary significantly during the one-way sensitivity analysis carried out on important model parameters and assumptions except when the utility value for ESRD was decreased by more than 30%. Conclusion Applying a cost-effectiveness threshold of £30,000 per QALY, the model shows it is cost-effective to follow current treatment guidelines and treat all patients who are not adequately maintained on CC (serum phosphorus above 5.6 mg/dl) with second-line LC. This is particularly the case for patients with serum phosphorus above 6.6 mg/dl. Our estimates are probably conservative as the possible compliance difference in favor of LC and the reduced number of hypercalcemic events with LC relative to CC was not considered.

A comparison of calcium-based phosphorus binders for patients with chronic kidney disease

Hyperphosphatemia in patients with end-stage renal disease (ESRD) is associated with secondary hyperparathyroidism and renal osteodystrophy, and is independently associated with an increased risk of mortality. Therefore, tight control of serum phosphorus is considered essential in these patients. Ideally, the best phosphorus binder would be inexpensive, nontoxic, well tolerated, and potent. Currently, calcium-based binders are generally considered first-line agents for the treatment of hyperphosphatemia in ESRD. However, excessive calcium absorption may produce hypercalcemia and possibly soft-tissue and vascular deposition. Calcium carbonate is a widely used effective, inexpensive, over-the-counter phosphate binder. Calcium acetate is an alternative phosphorus binder that is a more soluble and efficient phosphate binder. Equimolar doses of calcium acetate bind twice as much phosphorus as calcium carbonate. As a result, phosphorus binding can be achieved with a lower dose of calcium. The NKF/K-DOQI guidelines state that the total dose of elemental calcium provided by calcium-based phosphate binders should not exceed 1,500 mg/day. Calcium acetate more readily permits optimal phosphorus binding within these guidelines. This review focuses on calcium binders.

Lanthanum carbonate versus standard therapy for the treatment of hyperphosphatemia: safety and efficacy in chronic maintenance hemodialysis patients

No conventional phosphate binder is entirely satisfactory for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). Consequently, there is a need for new agents. One such agent is lanthanum carbonate (La). This large-scale study compares the safety of La with standard therapy (any approved phosphate binder) in patients who were treated for up to 2 years. Efficacy, having previously been demonstrated, was a secondary endpoint. After washout, patients were randomized to receive La (n=682) or their pre-study phosphate binder (n=677). Over a 6-week period, La was titrated to a maximum daily dose of 3000 mg elemental lanthanum (serum phosphorus target levels for titration were < or = 5.9 mg/dl (1.90 mmol/l)). Safety assessments included adverse events (AEs), full laboratory parameters and blood profiles. Efficacy assessments included serum phosphorus, calcium, calcium x phosphorus product and parathyroid hormone (PTH) levels. Average treatment exposure was greater in the standard therapy group (501.4 days) than in the La group (370.3 days) because standard therapy patients who switched or combined treatments were allowed to continue in the study. The most common AEs were gastrointestinal. The incidences of AEs in the La and treatment exposure-corrected standard therapy groups were nausea, 37 versus 29%; vomiting, 27 versus 22% and diarrhea (24% in each group). Hypercalcemia that was reported as an AE (La versus treatment exposure-corrected standard therapy) occurred in 4.3% and 8.4% of patients, respectively. There was no indication of liver toxicity, suppression of erythropoiesis or changes in the mini-mental state examination. Over 2 years, phosphorus control was similar in both groups; in the La group, however, serum calcium was lower and serum PTH levels were maintained in the range recommended by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI). The 2-year tolerability and efficacy of La are similar to those seen with standard therapy, although lower serum calcium levels and improved PTH levels were observed in the La group. These results support La as a viable new option for the management of hyperphosphatemia in ESRD.

Lanthanum Carbonate Treatment of Hyperphosphatemia in End-Stage Renal Disease

Objective: To review the literature on the safety and efficacy of lanthanum carbonate for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). Data Sources: Primary literature was obtained through a PubMed search (1966–September 2005) using the key terms Fosrenol and lanthanum carbonate. The FDA review, manufacturer-provided data, and published abstracts on lanthanum carbonate were also reviewed and evaluated. Study Selection and Data Extraction: Human studies in which lanthanum carbonate was compared with placebo or active control for the treatment of hyperphosphatemia secondary to renal disease were included. Dose-titration studies were excluded. Data Synthesis: Phosphate-lowering agents and dietary phosphate restriction are currently the first-line therapies for initial treatment of hyperphosphatemia associated with ESRD. Lanthanum carbonate is a highly effective non–aluminum, non–calcium-containing phosphate binder. It is the only FDA-approved phosphate binder that is available as an unflavored chewable tablet that may be taken without water. Conclusions: Clinical studies demonstrate that lanthanum carbonate is more effective than placebo but as or less effective than standard therapies in lowering serum phosphate to target levels. When compared with calcium salts, lanthanum carbonate had a lower incidence of hypercalcemia and a lower risk of patients developing bone disease. However, in clinical trials, patients receiving lanthanum carbonate had greater discontinuation rates, some due to adverse events. The long-term safety data (&gt;5 y), including the potential for lanthanum accumulation in the bone with subsequent development of osteodystrophy, remain unknown.

Randomized, double-blind, placebo-controlled, dose-titration, phase III study assessing the efficacy and tolerability of lanthanum carbonate: a new phosphate binder for the treatment of hyperphosphatemia

Background:Lanthanum carbonate is a novel, non-calcium, non-aluminum phosphate binder under evaluation for the treatment of hyperphosphatemia in end-stage renal disease (ESRD) patients receiving either hemodialysis or continuous ambulatory peritoneal dialysis. Methods:This 16-week study assessed the control of serum phosphorus with lanthanum carbonate, and its effects on serum calcium, calcium × phosphorus product, and parathyroid hormone (PTH). Hemodialysis patients ≥18 years old entered into a 1- to 3-week washout period during which serum phosphorus levels rose to >5.9 mg/dL (1.90 mmol/L). In total, 126 patients were titrated with lanthanum carbonate at doses containing 375, 750, 1,500, 2,250, or 3,000 mg/d elemental lanthanum, given in divided doses with meals over a 6-week period, to achieve serum levels ≤5.9 mg/dL. By the end of dose titration, 11/126 (9%) patients received ≤750 mg/d of lanthanum, 25 (20%) received 1,500 mg/d, 37 (29%) received 2,250 mg/d, and 53 (42%) received 3,000 mg/d. Following titration, patients were randomized to receive either lanthanum carbonate or placebo during a 4-week, double-blind maintenance phase. Results:At the study endpoint, the mean difference in serum phosphorus between the lanthanum carbonate and placebo treatment arms was 1.91 mg/dL (0.62 mmol/L) (P < 0.0001). Calcium × phosphorus product (P < 0.0001) and serum PTH levels (P < 0.01) were also significantly lower with lanthanum carbonate versus placebo. The incidence of drug-related adverse events was similar between placebo- and lanthanum carbonate-treated patients. Conclusion:Lanthanum carbonate is an effective and well-tolerated agent for the treatment of hyperphosphatemia in patients with ESRD.

Hyperphosphatemia in end-stage renal disease.

Hyperphosphatemia occurs universally in end-stage renal disease (ESRD) unless efforts are made to prevent positive phosphate balance. Positive phosphate balance results from the loss of renal elimination of phosphate and continued obligatory intestinal absorption of dietary phosphate. Increased efflux of phosphate from bone because of excess parathyroid hormone-mediated bone resorption can also contribute to increased serum phosphate concentrations in the setting of severe hyperparathyroidism. It is important to treat hyperphosphatemia because it contributes to the pathogenesis of hyperparathyroidism, vascular calcifications, and increased cardiovascular mortality in ESRD patients. Attaining a neutral phosphate balance, which is the key to the management of hyperphosphatemia in ESRD, is a challenge. Control of phosphorus depends on its removal during dialysis and the limitation of gastrointestinal absorption by dietary phosphate restriction and chelation of phosphate. Knowledge of the quantitative aspects of phosphate balance is useful in optimizing our use of phosphate binders, dialysis frequency, and vitamin D sterols. The development of new phosphate binders and efforts to find new ways to inhibit gastrointestinal absorption of phosphate will lead to improvements in the control of serum phosphate levels in ESRD.

Poly[allylamine hydrochloride] (RenaGel): A noncalcemic phosphate binder for the treatment of hyperphosphatemia in chronic renal failure

Dietary phosphate restriction and the oral administration of calcium and aluminum salts have been the principal means of controlling hyperphosphatemia in individuals with end-stage renal disease over the past decade. Although relatively well-tolerated, a large fraction of patients treated with calcium develop hypercalcemia, particularly when administered concurrently with calcitriol, despite a lowering of the dialysate calcium concentration. We evaluated the efficacy of cross-linked poly[allylamine hydrochloride] (RenaGel; Geltex Pharmaceuticals, Waltham, MA), a nonabsorbable calcium- and aluminum-free phosphate binder, in a randomized, placebo-controlled, double-blind trial of 36 maintenance hemodialysis patients followed over an 8-week period. RenaGel was found to be as effective as calcium carbonate or acetate as a phosphate binder. The reduction in serum phosphorus was significantly greater after 2 weeks of treatment with RenaGel (6.6 ± 2.1 mg/dL to 5.4 ± 1.5 mg/dL) compared with placebo (7.0 ± 2.1 mg/dL to 7.2 ± 2.4 mg/dL; P = 0.037). There was no significant change in serum calcium concentration in either treatment group. The total serum cholesterol and low-density lipoprotein cholesterol fraction were significantly reduced in RenaGel-treated patients compared with placebo-treated patients ( P = 0.013 and P = 0.003, respectively) without a concomitant reduction in high-density lipoprotein cholesterol ( P = 0.93). There was no difference among recipients of RenaGel and placebo in terms of adverse events. RenaGel is a safe and effective alternative to oral calcium for the management of hyperphosphatemia in end-stage renal disease.