Calcium-based Phosphate Binders Research Articles

Relationship of FGF23 to indexed left ventricular mass in children with non-dialysis stages of chronic kidney disease.

The aim of this study was to evaluate the association of serum intact fibroblast growth factor 23 (FGF23) concentrations with indexed left ventricular mass in children with non-dialysis stages 3-5 of chronic kidney disease (CKD). The study cohort comprised 83 children (51 boys; mean age 12.1 ± 3.2 years) with a mean estimated glomerular filtration rate (eGFR) of 32.3 ± 14.6 ml/min/1.73 m(2) who underwent clinic and ambulatory blood pressure measurement (ABPM), echocardiography and evaluation of biochemical markers of CKD-associated mineral bone disease. The mean left ventricular mass index (LVMI) was 35.9 ± 8.5 g/m(2.7) (± standard deviation), with 30 (36.1 %) children showing left ventricular hypertrophy (LVH), all eccentric, as defined using age-specific criteria. For all subjects, the mean FGF23 concentration was 142.2 ± 204.4 ng/l and the normalised distribution following log transformation was 1.94 ± 0.39. There was significant univariate correlation of LVMI with GFR, body mass index (BMI) z-score and calcium intake, but not with 24-h systolic ABPM z-score, log intact parathyroid hormone or log FGF23. On multivariate analysis following adjustment for confounders, only elemental calcium content (g/kg/day) estimated from prescribed calcium-based phosphate binder dose (β = 154.9, p < 0.001) and BMI z-score (β = 2.397, p = 0.003) maintained a significant positive relationship with LVMI (model r (2) = 0.225). We observed no significant relationship of FGF23 with LVMI. Larger studies in children are needed to clarify the roles of calcium-containing phosphate binders and FGF23 with LV mass and their roles in the evolution of the development of adverse cardiovascular outcomes.

Iron-based phosphate binders: do they offer advantages over currently available phosphate binders?

Increased cardiovascular morbidity and mortality has been associated with the hyperphosphatemia seen in patients with end-stage chronic kidney disease (CKD). Oral phosphate binders are prescribed in these patients to prevent intestinal absorption of dietary phosphate and reduce serum phosphate. In prospective observational cohorts they have shown to decrease all-cause and cardiovascular mortality risk. Different problems have been associated with currently available phosphate binders as positive calcium balance and impaired outcomes with calcium-based phosphate binders or increased costs with non-calcium-based phosphate binders. Iron-based phosphate binders represent a new class of phosphate binders. Several iron-based phosphate binders have undergone testing in clinical trials. Ferric citrate (JTT-751) and sucroferric oxyhydroxide (PA21) are the two iron-based binders that have passed to the clinical field after being found safe and effective in decreasing serum phosphate. Iron from ferric citrate is partially absorbed compared to sucroferric oxyhydroxide. Ferric citrate usage could result in an important reduction in erythropoiesis-stimulating agent (ESA) and IV iron usage, resulting in significant cost savings. Sucroferric oxyhydroxide was effective in lowering serum phosphorus in dialysis patients with similar efficacy to sevelamer carbonate, but with lower pill burden, and better adherence. Ferric citrate may be more suited for the treatment of chronic hyperphosphatemia in CKD patients requiring iron supplements but its use may have been hampered by potential aluminum overload, as citrate facilitates its absorption; sucroferric oxyhydroxide may be more suited for hyperphosphatemic CKD patients not requiring iron supplementation, with low pill burden.

Use of vitamin D receptor activator, incident cardiovascular disease and death in a cohort of hemodialysis patients.

The use of vitamin D receptor activators (VDRAs) is an independent predictor of a lower risk of death from cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). We examined whether the use of VDRAs and other CKD-mineral bone disorder (MBD)-related factors are associated with incident CVD or death after CVD in hemodialysis patients. This is a historical cohort study of 37 690 prevalent hemodialysis patients without previous history of CVD at the end of 2004 extracted from a nationwide registry in Japan. The key exposure was the use of VDRAs, and the outcomes were incident CVD (myocardial infarction, cerebral infarction, cerebral hemorrhage, and sudden death) and death after CVD during the 1-year follow-up. VDRAs were used in 57% of the subjects at baseline. We identified 2433 patients with incident CVD and 397 deaths after the events. In multivariate logistic regression models, independent predictors of incident CVD were non-use of VDRA, higher intact PTH, non-use of calcium-based phosphate-binder, and non-use of non-calcium-based phosphate binder. Risk of death after CVD was not significantly associated with VDRA, whereas it was lower in those with lower corrected calcium, and the risk was higher in those with higher phosphate and in non-users of calcium-based phosphate binders. The use of VDRAs was associated with a lower risk of incident CVD but not with death after CVD in this large cohort of hemodialysis patients. The CKD-MBD-related predictors of poor outcomes are associated with the risk of incident CVD, the risk of death after CVD, or both.

Tip-toeing toward the finish line.

Tip-toeing toward the finish line.

The effects of non-calcium-based phosphate binders versus calcium-based phosphate binders on cardiovascular calcification and bone remodeling among dialysis patients: a meta-analysis of randomized trials

Background: Vascular calcification significantly increases the rates of cardiovascular mortality in hemodialysis (HD) patients. Abnormalities in mineral metabolism may play a role in the pathogenesis of arterial calcification. Whether patients treated with non-calcium-based phosphate binders had reduced aortic vascular calcification compared to those treated with calcium-based phosphate binders is still unclear. Methods: We searched multiple databases for studies published through August 2013 that evaluated the effects of non-calcium-based phosphate binders (NCBP) versus calcium-based phosphate binders (CBP) on cardiovascular calcification and bone remodeling among dialysis patients. We summarized test performance characteristics with the use of forest plots, fixed and random effects models, and Egger regression test. Results: Eighteen eligible randomized controlled trials totaling 3676 patients were included. Meta-analysis results showed NCBP could significantly attenuate the progression of coronary artery calcification than CBP (WMD: −144.62, 95% CI: −285.62 to −3.63). The serum calcium levels significant lower in NCPB group than in CPB groups (WMD: −0.26, 95% CI: −0.37 to −0.14), but the serum iPTH levels were significantly higher in NCPB groups (WMD: 57.1, 95% CI: 13.42 to 100.78). The osteoid volume and osteoblast numbers were significant higher in NCPB group than in CPB group (WMD: 1.75, 95% CI: 0.78 to 2.73 for osteoid volume; WMD: 4.49, 95% CI: 1.83 to 7.15 for osteoblast numbers). The Egger regression test also showed no potential publication bias (p = 0.725). Conclusions: Based on available data, NCBPs have equally effective with CBPs for serum phosphate control. But there was significantly lower incidence of coronary artery calcification and a significant higher bone formatting rate in NCBP groups than in CBP groups. So we recommend NCBPs as phosphate binders for HD patients.

Practice patterns of phosphate binder use and their associations with mortality in chronic kidney disease.

Higher serum phosphorus is associated with an increased mortality among those with chronic kidney disease (CKD). We examined the practice patterns of phosphate binder use to lower serum phosphorus levels and their associations with mortality in the non-dialysisdependent CKD population. We examined the factors associated with the use of calcium and non-calcium phosphate binders in those with stage 3 and 4 CKD (eGFR 15 - 59 mL/min/1.73 m2) using logistic regression models. The associations between phosphate binder use and mortality were studied using propensity based analysis. Out of 57,928 patients with eGFR 15 - 59 mL/min/1.73 m2, 13,325 (23%) patients had serum phosphorus levels measured. 945 patients were prescribed phosphate binders, with 238 (25%) of them prescribed non-calcium-based phosphate binders and the rest calcium-based phosphate binders. Higher BMI, higher serum phosphorus, and higher serum calcium were associated with higher odds of being prescribed a non-calcium-based binder. Phosphate binder use was not significantly associated with mortality in either the entire cohort or the matched cohort in the analysis limited to those who were treated for at least 6 months. In the matched cohort, those who were treated for 1 year with a phosphate binder had a non-significant lower mortality rate (hazard ratio (HR): 0.85, 95% CI 0.66, 1.10). Phosphate binder use for 6 months and 1 year was not associated with reduced mortality in those with stage 3 and stage 4 CKD.

Calcium Balance and Negative Impact of Calcium Load in Peritoneal Dialysis Patients

Like hemodialysis patients, peritoneal dialysis (PD) patients are facing an excessively increased burden of vascular and valvular calcification. According to some surveys, more than 80% of prevalent PD patients are complicated with vascular calcification, and more than one third have heart valve calcification. Dysregulated phosphate metabolism is well recognized to play an important role in inducing vascular calcification, but increasing evidence is suggesting that dysregulated calcium metabolism also promotes vascular calcification and might in fact be more potent than phosphate in inducing that calcification. Growing evidence from randomized controlled trials shows more progression of vascular calcification and higher mortality among chronic kidney disease (CKD) patients receiving calcium-based phosphate binders than among those receiving non-calcium-containing phosphate binders. Those results raise important safety concern about the use of high-dose calcium-based phosphate binders in the CKD population, including both non-dialysis and dialysis patients (especially anuric dialysis patients), who have markedly reduced urinary calcium excretion. To prevent calcium overload, this review recommends restricting the dose of calcium-based phosphate binders in CKD patients, especially those who are elderly, who have increased cardiovascular risk, who already have baseline vascular or valvular calcification, or who have low intact parathyroid hormone and adynamic bone disease.

Clinical and economic aspects of sevelamer therapy in end-stage renal disease patients.

Phosphate control is still a great challenge in chronic kidney disease (CKD), and in spite of the great improvements in dialysis techniques, achievement of the goals for mineral metabolism control is still far from ideal. Aluminum hydroxide has been largely abandoned due to the high risk of aluminum toxicity, while the use of calcium-based phosphate binders may cause hypercalcemia, overzealous parathyroid suppression, and extraskeletal calcification. Sevelamer hydrochloride has been introduced as an efficient medication for phosphate control, with a lower risk of hypercalcemia and parathyroid suppression. Various clinical trials have compared the risk of vascular calcification between sevelamer and calcium salts with inconsistent results. In spite of these inconsistencies, the Kidney Disease Outcomes Quality Initiative (KDOQI) suggests non-calcium phosphate binders as the preferred phosphate binder in dialysis patients with severe vascular and/or other soft-tissue calcifications and in those with hypercalcemia or parathyroid hormone (PTH) <150 mg/dL. The Kidney Disease Improving Global Outcome (KDIGO) limits the use of non-calcium phosphate binders to patients with hypercalcemia. Regarding the effect on mortality, the results of clinical trials are again inconsistent. The other important aspect of using sevelamer is the issue of price, which is substantially higher than calcium-based phosphate binders. Reviewing the studies on economic aspects shows that sevelamer increases quality-adjusted life-years (QALY) and possibly life years, with a higher cost compared to calcium-based phosphate binders. In conclusion, sevelamer is a very useful drug for phosphate control, reduction of hypercalcemia, and lessening the risk of adynamic bone disease, with probable reduction in vascular calcification and possible reduction in mortality rate. It has a higher economic burden on health care systems compared to calcium-based phosphate binders. This may affect its extensive use according to guideline recommendations, and will be influenced by local health care budgets and the decision of health care strategists.

Sevelamer carbonate: a review in hyperphosphataemia in adults with chronic kidney disease.

Sevelamer carbonate (Renvela(®)), a buffered form of sevelamer hydrochloride (Renagel(®)), is an orally administered non-absorbed phosphate-binding anion exchange resin used in the treatment of hyperphosphataemia in chronic kidney disease (CKD). In the EU, sevelamer carbonate is approved in adult CKD patients who require dialysis and in those who do not require dialysis with serum phosphate levels ≥ 1.78 mmol/L, whereas in the USA sevelamer carbonate is approved in adult CKD patients who require dialysis. Sevelamer carbonate and sevelamer hydrochloride achieved similar reductions in serum phosphate levels in randomized comparative trials in patients with CKD receiving haemodialysis; sevelamer carbonate also reduced serum phosphate levels in noncomparative studies in CKD patients not requiring dialysis. The most common adverse events with sevelamer carbonate are gastrointestinal in nature. Sevelamer has pleiotropic effects, such as improving the serum lipid profile and attenuating endothelial and cardiovascular risk factors in CKD. All formulations of sevelamer have markedly higher acquisition costs than calcium-based phosphate binders. Cost-effectiveness analyses focusing specifically on sevelamer carbonate have not been conducted, and those based on clinical trial data with sevelamer hydrochloride have provided both favourable and unfavourable results compared with calcium-based phosphate binders, reflecting heterogeneity between modelled analyses in terms of data sources, assumptions, comparators, geographical regions, type of costs included and other factors. Although well-designed studies evaluating the impact of phosphate binders on hard clinical endpoints appear to be warranted, sevelamer carbonate may be particularly useful for the treatment of patients at risk of metabolic acidosis (offering advantages over sevelamer hydrochloride in this regard) and for individuals requiring treatment with a phosphate binding agent that does not contain aluminium or calcium.

Is chronic kidney disease-mineral bone disorder (CKD-MBD) really a syndrome?

The concept of chronic kidney disease-mineral bone disorder (CKD-MBD) does not appear to fulfil the requirements for a syndrome at first glance, but its definition has brought some clear-cut benefits for clinicians and patients, including wider and more complex diagnostic and therapeutic approaches to the management of this challenging set of issues. Admittedly, not all components of CKD-MBD are present in all patients at all times, but these are highly interrelated, involving mineral and bone laboratory abnormalities, clinical and histological bone disease and finally, cardiovascular disease. The presence of typical biological bone ossification processes in an ectopic anatomical location in CKD has helped to define the existence of an unprecedented bone-vascular relationship, extending its interest even to other medical specialities. For now, we believe that CKD-MBD does not reach full criteria to be defined as a syndrome. However, this novel concept has clearly influenced current clinical guidelines. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF/KDOQI™) guidelines in 2003 for instance recommended that calcium-based phosphate binders should be avoided to treat hyperphosphataemia in the presence of cardiovascular calcifications. In 2009, the KDIGO and other guidelines reinforced and extended this recommendation by stating that it is reasonable to choose oral phosphate binder therapy by taking into consideration other components of CKD-MBD. Similarly, it is also considered reasonable to use information on vascular/valvular calcification to guide the management of CKD-MBD. Our current assumption as a working group 'CKD-MBD' is that CKD-MBD has the potential to be defined a true syndrome, such as a constellation of concurrent signs and symptoms that suggest a common underlying mechanism for these components as opposed to the term disease. The term 'syndrome' also implies that in any patient at risk due to the presence of one or a few components of the entire syndrome, the screening for additional components is highly recommended. However, it has not currently been demonstrated that there is an additive predictive value, which can be derived from identifying individual components. Despite all we have learned about this putative syndrome, we have been left with only a hypothetical framework about how to treat patients. So while we agree that the concept of CKD-MBD has influenced, and continues to influence, our current clinical hypotheses, definitive proof of a benefit of interventions in CKD-MBD is still lacking and a global-multiple therapeutic approach to treat simultaneously several components of CKD-MBD should be tested by well-designed new randomized controlled trials.

Investigating the Role of Cardiovascular Biomarkers in Children with Pre-Dialysis Chronic Kidney Disease: A Substitute to Echocardiography to Detect Increased Left Ventricular Mass?

Background: Children with chronic kidney disease (CKD) are at increased risk of future cardiovascular (CV) events. Our aim in this prospective single-centre cross-sectional analysis was to assess the relationship of a novel panel of CV biomarkers with left ventricular hypertrophy (LVH). Methods: A panel of five CV biomarkers (asymmetric dimethyl arginine, high sensitivity C-reactive protein, homocysteine, N-terminal pro-B type natriuretic peptide and uric acid) were measured on the same day as an echocardiogram assessment, in paediatric patients with pre-dialysis stages 3-5 of CKD. Results: Of 73 children aged 5-18 years, LVH, all eccentric, was identified in 38%. Systolic blood pressure (BP), glomerular filtration rate (GFR) and higher intake of calcium-based phosphate binders were significantly worse in children with LVH. In multivariate models analysing each biomarker one at a time with confounders [GFR, systolic BP z-score, anti-hypertensive medication (yes/no) and elemental calcium intake], clinic systolic BP z-score and elemental calcium intake consistently displayed a significant relationship with indexed left ventricular mass (LVMI). None of the evaluated CV biomarkers displayed a significant relationship with LVMI. Conclusions: In our cohort of children with moderately severe pre-dialysis CKD we have identified no suitable biomarkers to detect LVH. We would therefore recommend that echocardiographic determination of LVMI remains the technique of choice for detection of LVH in children with CKD.

Review: Non–calcium-based phosphate binders reduce mortality compared with calcium-based binders in CKD

Source Citation Jamal SA, Vandermeer B, Raggi P, et al. Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systemati...

Low Dose Nicotinamide as an Adjunctive Therapy to Calcium Carbonate for Control of Hyperphosphatemia in Hemodialysis Patients

Abstract Background: Hyperphosphatemia remains a common problem in patients on maintenance dialysis and contributes to the development of secondary hyperparathyroidism. Current therapies for the treatment of hyperphosphatemia are frequently insufficient to achieve the recommended K/DOQI goal of maintaining serum phosphorus level between 3.5 and 5.5 mg/dl. Niacinamide inhibits intestinal sodium/ phosphorus co transporters and reduces serum phosphorus level in some clinical studies. So, we aimed to evaluate the safety and the efficacy of nicotinamide as adjunctive therapy to calcium carbonate (as calcium based phosphate binder) in hemodialysis patients. Methods: Sixty hemodialysis patients with serum phosphorus level ≥ 5.0 mg/dl were randomly assigned to 8 weeks of the study. Patients were divided into two groups:(group I) (control group): 30 cases calcium carbonate only and (group II) (study group): 30 cases received a combination of calcium carbonate and nicotinamide. Nicotinamide dose was started as 500mg/day and increased on 8th day to 1000 mg/day. Results:In the study group (nicotinamide group): serum phosphorus level fell significantly (p 0.05). Intact parathyroid hormone, uric acid, platelet count, total cholesterol, hemoglobin, ASAT, and ALAT and lipid profile remained insignificantly changed in both groups. Diarrhea, flushing and skin rash were the major adverse effects seen with nicotinamide therapy resulting in early withdrawal of 4 patients from the study. Conclusion: In hemodialysis patients, nicotinamide in single dose of 1000 mg daily can effectively reduce serum phosphorus level when administered with calcium carbonate (as phosphate binder) with less potential side effects reported.

Epicardial adipose tissue predicts mortality in incident hemodialysis patients: a substudy of the Renagel in New Dialysis trial

Epicardial adipose tissue (EAT) has been described in the general population as an independent risk marker for incident coronary artery disease. In hemodialysis patients, it correlates with other markers of cardiovascular disease, but it is unknown if it is associated with adverse events. post hoc analysis of the Renagel in New Dialysis (RIND) patients study, a randomized trial of sevelamer versus calcium-based phosphate binders in 109 incident hemodialysis patients, followed for all-cause mortality for a median of 49.3 months. Patients underwent baseline cardiac computed tomography imaging within 120 days of dialysis initiation. Baseline EAT measurements were available in 95 patients; EAT was positively correlated with age, body mass index, triglycerides, C-reactive protein, coronary artery calcium and aortic calcium, and negatively correlated with systolic and diastolic blood pressure, serum high density lipoprotein (HPL) cholesterol and serum phosphate (all P < 0.05). During follow-up, a total of 27 (28.4%) patients expired [mortality per 1000 patients/year: 95% confidence interval (95% CI) = 77 (64-94)]. Five-year survival rate was 44. 6% (95% CI: 21.1-65.7) and 71.2% (95% CI: 45.95-86.25) in patients with EAT above or below the median, respectively. Each 10 cc increase in EAT volume was associated with a significant 6% increase in the risk of death during follow-up [hazard ratio (HR): 1.060; 95% CI: 1.013-1.109; P-value = 0.012]. In this subanalysis of a randomized trial, EAT was an independent predictor of mortality in incident hemodialysis patients after ~4 years of follow-up. These hypothesis-generating findings will need confirmatory evidence.

Effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease: an updated systematic review and meta-analysis

Phosphate binders (calcium-based and calcium-free) are recommended to lower serum phosphate and prevent hyperphosphataemia in patients with chronic kidney disease, but their effects on mortality and cardiovascular outcomes are unknown. We aimed to update our meta-analysis on the effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease. We did a systematic review of articles published in any language after Aug 1, 2008, up until Oct 22, 2012, by searching Medline, Embase, International Pharmaceutical Abstracts, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature. We included all randomised and non-randomised trials that compared outcomes between patients with chronic kidney disease taking calcium-based phosphate binders with those taking non-calcium-based binders. Eligible studies, determined by consensus with predefined criteria, were reviewed, and data were extracted onto a standard form. We combined data from randomised trials to assess the primary outcome of all-cause mortality using the DerSimonian and Laird random effects model. Our search identified 847 reports, of which eight new studies (five randomised trials) met our inclusion criteria and were added to the ten (nine randomised trials) included in our previous meta-analysis. Analysis of the 11 randomised trials (4622 patients) that reported an outcome of mortality showed that patients assigned to non-calcium-based binders had a 22% reduction in all-cause mortality compared with those assigned to calcium-based phosphate binders (risk ratio 0·78, 95% CI 0·61-0·98). Non-calcium-based phosphate binders are associated with a decreased risk of all-cause mortality compared with calcium-based phosphate binders in patients with chronic kidney disease. Further studies are needed to identify causes of mortality and to assess whether mortality differs by type of non-calcium-based phosphate binder. None.

The demise of calcium-based phosphate binders

In The Lancet, Sophie Jamal and colleagues1 report an updated systematic review and meta-analysis of the effect on mortality of treatment of chronic kidney disease hyperphosphataemia with calcium-based versus non-calcium-based phosphate binders. Kidneys excrete excess dietary phosphate, therefore loss of renal function leads to a positive phosphate balance that ultimately results in hyperphosphataemia. Excess phosphate might deposit in soft tissues, most notably the cardiovascular system, as calcium phosphate salts.

Effect of a magnesium-based phosphate binder on medial calcification in a rat model of uremia

Calcium-based phosphate binders are used to control hyperphosphatemia; however, they promote hypercalcemia and may accelerate aortic calcification. Here we compared the effect of a phosphate binder containing calcium acetate and magnesium carbonate (CaMg) to that of sevelamer carbonate on the development of medial calcification in rats with chronic renal failure induced by an adenine diet for 4 weeks. After 1 week, rats with chronic renal failure were treated with vehicle, 375 or 750 mg/kg CaMg, or 750 mg/kg sevelamer by daily gavage for 5 weeks. Renal function was significantly impaired in all groups. Vehicle-treated rats with chronic renal failure developed severe hyperphosphatemia, but this was controlled in treated groups, particularly by CaMg. Neither CaMg nor sevelamer increased serum calcium ion levels. Induction of chronic renal failure significantly increased serum PTH, dose-dependently prevented by CaMg but not sevelamer. The aortic calcium content was significantly reduced by CaMg but not by sevelamer. The percent calcified area of the aorta was significantly lower than vehicle-treated animals for all three groups. The presence of aortic calcification was associated with increased sox9, bmp-2, and matrix gla protein expression, but this did not differ in the treatment groups. Calcium content in the carotid artery was lower with sevelamer than with CaMg but that in the femoral artery did not differ between groups. Thus, treatment with either CaMg or sevelamer effectively controlled serum phosphate levels in CRF rats and reduced aortic calcification.

Clinical efficacy of sevelamer hydrochloride in patients with end-stage renal disease: a retrospective study

Sevelamer hydrochloride (Renagel) is frequently used as a second-line phosphate binder in patients on renal replacement therapy. Many studies have shown that sevelamer can improve vascular calcification, serum uric acid and low-density lipoprotein (LDL) cholesterol levels. The main objectives of this study were to assess the efficacy of sevelamer against calcium-based phosphate binders, as well as its tolerability and side-effect profile. This was a retrospective study that included all patients on renal replacement therapy (between 2008 and 2011) who had previously received calcium-based binders for ≥ 6 months and were subsequently switched to sevelamer. Data collected from the patients' medical records included demographics, as well as renal parameters three months prior to sevelamer treatment, and at three and six months post treatment. The study excluded patients on multiple, concomitant phosphate binders or with functioning renal transplants, and those who were noncompliant or had inadequate follow-up blood investigations. A total of 39 patients were included in the study. No major side effects were reported by any of the patients. There were improvements in calcium, phosphate, uric acid and LDL cholesterol levels at three and six months post-sevelamer treatment. We found sevelamer to be superior to calcium-based phosphate binders in reducing serum calcium, phosphate, uric acid and LDL cholesterol levels in our patient population with advanced renal bone disease. Sevelamer also appears to be well tolerated with no significant side effects.

PA21, a New Iron-Based Noncalcium Phosphate Binder, Prevents Vascular Calcification in Chronic Renal Failure Rats

Chronic renal failure (CRF) is associated with the development of secondary hyperparathyroidism and vascular calcifications. We evaluated the efficacy of PA21, a new iron-based noncalcium phosphate binder, in controlling phosphocalcic disorders and preventing vascular calcifications in uremic rats. Rats with adenine-diet-induced CRF were randomized to receive either PA21 0.5, 1.5, or 5% or CaCO3 3% in the diet for 4 weeks, and were compared with uremic and nonuremic control groups. After 4 weeks of phosphate binder treatment, serum calcium, creatinine, and body weight were similar between all CRF groups. Serum phosphorus was reduced with CaCO3 3% (2.06 mM; P ≤ 0.001), PA21 1.5% (2.29 mM; P < 0.05), and PA21 5% (2.21 mM; P ≤ 0.001) versus CRF controls (2.91 mM). Intact parathyroid hormone was strongly reduced in the PA21 5% and CaCO3 3% CRF groups to a similar extent (1138 and 1299 pg/ml, respectively) versus CRF controls (3261 pg/ml; both P ≤ 0.001). A lower serum fibroblast growth factor 23 concentration was observed in the PA21 5%, compared with CaCO3 3% and CRF, control groups. PA21 5% CRF rats had a lower vascular calcification score compared with CaCO3 3% CRF rats and CRF controls. In conclusion, PA21 was as effective as CaCO3 at controlling phosphocalcic disorders but superior in preventing the development of vascular calcifications in uremic rats. Thus, PA21 represents a possible alternative to calcium-based phosphate binders in CRF patients.

Lanthanum Carbonate Delays Progression of Coronary Artery Calcification Compared With Calcium-Based Phosphate Binders in Patients on Hemodialysis

Coronary artery calcification (CAC) is associated with future cardiovascular events and/or death of patients on hemodialysis (HD). We investigated whether progression of CAC in patients on HD could be delayed by switching from a calcium (Ca)-based phosphate (Pi) binder to lanthanum carbonate. The CAC scores were evaluated at study enrollment and after 6 months in 52 patients on HD using calcium carbonate (CC) as a Pi binder. Patients were randomly divided into 2 groups assigned to receive either CC or lanthanum carbonate (LC), and the CAC scores were evaluated after a 6-month treatment period. Progression of CAC was assessed, as were serum levels of Ca, Pi, and intact parathyroid hormone (iPTH). Forty-two patients completed the study (23 receiving CC and 19 receiving LC). In the 6 months prior to randomization, all patients were treated with CC. During this 6-month period, the CAC scores increased significantly in all 42 patients. Once randomized, there was significantly less progression in the group treated with LC than with CC. Changes in CAC scores from 6 to 12 months were significantly smaller in the LC group than the CC group (-288.9 ± 1176.4 vs 107.1 ± 559.6, P = .036), and percentage changes were also significantly different (-6.4% vs 41.2%, P = .024). Serum Ca, Pi, and iPTH levels were similar in both groups during the study period. This pilot study suggested that LC delayed progression of CAC in patients on HD compared with CC.