Primary studies included in this systematic review

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Primary study

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Journal American journal of kidney diseases : the official journal of the National Kidney Foundation
Year 2011
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BACKGROUND: Some trials have indicated that coronary artery calcification progresses more slowly in sevelamer-treated dialysis patients than in those using calcium-based binders. Effects of phosphate binders on circulating advanced glycation end products (AGEs) are unknown. STUDY DESIGN: Randomized trial with parallel-group design. SETTING & PARTICIPANTS: 183 adult (aged >20 years) patients on maintenance hemodialysis therapy at 12 dialysis facilities with a mean vintage of 118 ± 89 (median, 108) months. Dialysate calcium concentration was 2.5 mEq/L, and dietary calcium was not controlled. INTERVENTION: Patients were randomly assigned to 12 months of treatment with sevelamer (n = 91) or calcium carbonate (n = 92). OUTCOMES & MEASUREMENTS: Primary outcome measures were change from baseline in coronary artery calcification score (CACS) determined at study entry and completion using multislice computed tomography and the proportion of patients with a ≥ 15% increase in CACS. Blood parameters were determined at study entry and 2-week intervals, and levels of plasma pentosidine, a representative AGE, were determined at study entry, 6 months, and study completion. RESULTS: 79 (86.8%) and 84 (91.3%) patients in the sevelamer and calcium-carbonate arms completed the treatment, respectively. Both binders were associated with an increase in mean CACS: 81.8 (95% CI, 42.9-120.6) and 194.0 (139.7-248.4), respectively (P < 0.001 for both). After adjustment for baseline values, the increase in the sevelamer group was 112.3 (45.8-178) less (P < 0.001). Percentages of patients with a ≥ 15% increase in CACS were 35% of the sevelamer group and 59% of the calcium-carbonate group (P = 0.002). Plasma pentosidine levels increased with calcium carbonate but not [corrected] sevelamer treatment (P < 0.001). Sevelamer use was associated with decreased risk of a ≥ 15% increase in CACS regardless of baseline blood parameters, pentosidine level, and CACS. LIMITATIONS: Treatment duration was relatively short, some sevelamer-treated patients (7 of 79) received calcium carbonate, and washout could not be performed. CONCLUSIONS: The data suggest that sevelamer treatment slowed the increase in CACS and suppressed AGE accumulation.

Primary study

Unclassified

Journal Nephron. Clinical practice
Year 2011
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Background: Fibroblast growth factor 23 (FGF23) concentrations increase early in chronic kidney disease (CKD), and the influence of current CKD-mineral and bone disorder (MBD) therapies on serum FGF23 levels is still under investigation. Methods: In this post-hoc analysis of a randomized clinical trial, phosphate binders and calcitriol were washed out of 72 hemodialysis patients who were then submitted to bone biopsy, coronary tomography and biochemical measures, including FGF23. They were randomized to receive sevelamer or calcium acetate for 1 year and the prescription of calcitriol and the calcium concentration in the dialysate were adjusted according to serum calcium, phosphate and PTH and bone biopsy diagnosis. Results: At baseline, bone biopsy showed that 58.3% had low-turnover bone disease, whereas 38.9% had high-turnover bone disease, with no significant differences between them with regard to FGF23. Median baseline FGF23 serum levels were elevated and correlated positively with serum phosphate. After 1 year, serum FGF23 decreased significantly. Repeated measures ANOVA analysis showed that the use of a 3.5-mEq/l calcium concentration in the dialysate, as well as the administration of calcitriol and a calcium-based phosphate binder were associated with higher final serum FGF23 levels.Conclusions: Taken together, our results confirm that the current CKD-MBD therapies have an effect on serum levels of FGF23. Since FGF23 is emerging as a potential treatment target, our findings should be taken into account in the decision on how to manage CKD-MBD therapy. Copyright © 2010 S. Karger AG, Basel.

Primary study

Unclassified

Journal Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Year 2010
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BACKGROUND: Phosphate binders are required to control serum phosphorus in dialysis patients. A phosphate binder combining calcium and magnesium offers an interesting therapeutic option. METHODS: This controlled randomized, investigator-masked, multicentre trial investigated the effect of calcium acetate/magnesium carbonate (CaMg) on serum phosphorus levels compared with sevelamer hydrochloride (HCl). The study aim was to show non-inferiority of CaMg in lowering serum phosphorus levels into Kidney Disease Outcome Quality Initiative (K/DOQI) target level range after 24 weeks. Three hundred and twenty-six patients from five European countries were included. After a phosphate binder washout period, 255 patients were randomized in a 1:1 fashion. Two hundred and four patients completed the study per protocol (CaMg, N = 105; dropouts N = 18; sevelamer-HCl, N = 99; dropouts N = 34). Patient baseline characteristics were similar in both groups. RESULTS: Serum phosphorus levels had decreased significantly with both drugs at week 25, and the study hypothesis of CaMg not being inferior to sevelamer-HCl was confirmed. The area under the curve for serum phosphorus (P = 0.0042) and the number of visits above K/DOQI (≤1.78 mmol/L, P = 0.0198) and Kidney disease: Improving global outcomes (KDIGO) targets (≤1.45 mmol/L, P = 0.0067) were significantly lower with CaMg. Ionized serum calcium did not differ between groups; total serum calcium increased in the CaMg group (treatment difference 0.0477 mmol/L; P = 0.0032) but was not associated with a higher risk of hypercalcaemia. An asymptomatic increase in serum magnesium occurred in CaMg-treated patients (treatment difference 0.2597 mmol/L, P < 0.0001). There was no difference in the number of patients with adverse events. CONCLUSION: CaMg was non-inferior to the comparator at controlling serum phosphorus levels at Week 25. There was no change in ionized calcium; there was minimal increase in total serum calcium and a small increase in serum magnesium. It had a good tolerability profile and thus may represent an effective treatment of hyperphosphataemia.

Primary study

Unclassified

Journal Journal of the Formosan Medical Association = Taiwan yi zhi
Year 2010
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Background/Purpose: Sevelamer hydrochloride is a recently developed phosphate binder, which is a quaternary amine anion exchanger without calcium or aluminum. Sevelamer is effective in controlling hyperphosphatemia without increasing the calcium load in chronic hemodialysis (HD) patients. We investigated whether sevelamer restored bone metabolism in chronic HD patients. Methods: An 8-week, prospective, open-label, randomized study was conducted after a 2-week washout period in chronic hyperphosphatemic HD patients. This study compared the effect of sevelamer on markers of bone turnover with that of calcium acetate, as stratified by baseline serum intact parathyroid hormone (iPTH) level. Results: There was no difference in the changes of serum phosphorus, calcium-phosphorus product and serum iPTH between the sevelamer and the calcium acetate groups. However, more hypercalcemic events (12%) were documented under calcium acetate treatment. In patients with hypoparathyroidism, calcium acetate treatment decreased serum iPTH at the end of the study, while sevelamer did not. Increased serum alkaline phosphatase levels were found among patients receiving sevelamer treatment compared with those who received calcium acetate treatment. In those patients receiving sevelamer, the serum alkaline phosphatase level was also positively correlated to the sevelamer dosage (r = 0.246, p = 0.013). Conclusion: Sevelamer effectively reduces serum phosphorus with a lower incidence of hypercalcemic effects in HD patients. Sevelamer is an effective means of treatment for chronic hyperphosphatemic HD patients, especially those with hypoparathyroidism. © 2010 Formosan Medical Association & Elsevier.

Primary study

Unclassified

Journal Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Year 2009
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Background. Inadequate phosphorus control is associated with increased morbidity and mortality in patients with CKD stage 5. Although phosphate binders are often used in patients on peritoneal dialysis (PD), no large randomized controlled studies evaluating their use solely in this population have previously been reported. Methods. In this multicentre, open-label study, adult patients on PD with serum phosphorus >5.5 mg/dl were randomized (2:1) to 12 weeks of treatment with sevelamer hydrochloride or calcium acetate. Doses were titrated to achieve serum phosphorus of 3.0-5.5 mg/dl. Changes in serum phosphorus, calcium, intact parathyroid hormone (iPTH), lipids and plasma biomarkers were assessed. Results. A total of 253 patients were screened, 143 of whom were randomized (sevelamer hydrochloride, n = 97; calcium acetate, n = 46). Treatment groups were well balanced with regard to baseline demographics. Serum phosphorus levels were significantly reduced after 12 weeks with both sevelamer hydrochloride and calcium acetate (P < 0.001). Serum PTH was also reduced in both groups while serum calcium increased in the calcium acetate group (P = 0.001) but not in the sevelamer hydrochloride group. Sevelamer hydrochloride was also associated with decreases in total cholesterol, low-density lipoprotein cholesterol and uric acid and an increase in bone-specific alkaline phosphatase (all P < 0.001 versus baseline). Both treatments were well tolerated and safety profiles were consistent with previous reports in haemodialysis patients. Hypercalcaemia was experienced by more calcium acetate-treated patients (18 versus 2%; P = 0.001). Conclusions. In summary, sevelamer hydrochloride provides a reduction in serum phosphorus compared to that obtained with calcium-based binders in PD patients. The effects of sevelamer hydrochloride appear similar in both PD and haemodialysis populations. © The Author [2008]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Primary study

Unclassified

Journal Nephron. Clinical practice
Year 2008
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BACKGROUND/AIM: Vascular calcification is thought to be associated with a high cardiovascular mortality rate in patients with end-stage renal disease. Control of hyperphosphataemia is important for the treatment of the vascular calcification. The aim of the present study was to evaluate the effects of sevelamer hydrochloride on the progression of aortic calcification in haemodialysis (HD) patients. METHODS: 42 HD patients were studied in this study and divided into two groups (sevelamer vs. calcium). Sevelamer was added and titrated up to achieve serum P control for 6 months. The estimations of aortic calcification index (ACI) by abdominal computed tomography scans were performed twice in each patient. We compared the changes in serum calcium, phosphorus, intact parathyroid hormone, and lipids in two groups. RESULTS: Serum phosphorus levels decreased significantly from 6.7 +/- 0.7 to 6.2 +/- 0.5 mg/dl with no changes in serum intact parathyroid hormone levels in the sevelamer group (p < 0.01), and increased from 6.5 +/- 1.0 to 6.7 +/- 1.1 mg/dl in the calcium group (p < 0.05). Serum calcium levels did not change in the sevelamer group and calcium group. The serum levels of total cholesterol decreased significantly from 158.5 +/- 20.7 to 146.2 +/- 24.1 mg/dl (p = 0.024) and the low-density lipoprotein cholesterol level from 65.3 +/- 14.4 to 54.7 +/- 11.6 mg/dl (p = 0.014) in the sevelamer group. Serum C-reactive protein decreased significantly from 0.14 +/- 0.13 to 0.08 +/- 0.11 mg/dl in the sevelamer group (p = 0.038) and significantly increased (0.18 +/- 0.09 vs. 0.22 +/- 0.12 mg/dl) in the calcium group (p = 0.042). The mean changes in ACI (DeltaACI) were 3.6 +/- 1.5% in the sevelamer group and 8.2 +/- 3.1% in the calcium group. CONCLUSIONS: Sevelamer allows a better serum phosphorus control compared with calcium-based phosphate binder and suppresses the progression of aortic calcification in HD patients.

Primary study

Unclassified

Journal Nephron. Clinical practice
Year 2008
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Backgroundand Aims: Calcium-containing phosphate binders have been shown to increase the progression of vascular calcification in hemodialysis patients. This is a prospective study that compares the effects of calcium acetate and sevelamer on coronary calcification (CAC) and bone histology. Methods: 101 hemodialysis patients were randomized for each phosphate binder and submitted to multislice coronary tomographies and bone biopsies at entry and 12 months. Results: The 71 patients who concluded the study had similar baseline characteristics. On follow-up, the sevelamer group had higher levels of intact parathyroid hormone (498 ± 352 vs. 326 ± 236 pg/ml, p = 0.017), bone alkaline phosphatase (38 ± 24 vs. 28 ± 15 U/l, p = 0.03) and deoxypyridinoline (135 ± 107 vs. 89 ± 71 nmol/l, p = 0.03) and lower LDL cholesterol (74 ± 21 vs. 91 ± 28 mg/dl, p = 0.015). Phosphorus (5.8 ± 1.0 vs. 6 ± 1.0 mg/dl, p = 0.47) and calcium (1.27 ± 0.07 vs. 1.23 ± 0.08 mmol/l, p = 0.68) levels did not differ between groups. CAC progression (35 vs. 24%, p = 0.94) and bone histological diagnosis at baseline and 12 months were similar in both groups. Patients of the sevelamer group with a high turnover at baseline had an increase in bone resorption (eroded surface, ES/BS = 9.0 ± 5.9 vs. 13.1 ± 9.5%, p = 0.05), whereas patients of both groups with low turnover at baseline had an improvement in bone formation rate (BFR/BS = 0.015 ± 0.016 vs. 0.062 ± 0.078, p = 0.003 for calcium and 0.017 ± 0.016 vs. 0.071 ± 0.084 μm3/μm2/day, p = 0.010 for sevelamer). Conclusions: There was no difference in CAC progression or changes in bone remodeling between the calcium and the sevelamer groups. Copyright © 2008 S. Karger AG.

Primary study

Unclassified

Authors St Peter WL , Liu J , Weinhandl E , Fan Q
Journal American journal of kidney diseases : the official journal of the National Kidney Foundation
Year 2008
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BACKGROUND: The Dialysis Clinical Outcomes Revisited (DCOR) trial, a large, randomized, multicenter, open-label study, compared effects of sevelamer with calcium-based phosphate binders on mortality and hospitalization in hemodialysis patients. Many patients were lost to follow-up, precluding intent-to-treat analysis by using prospective data collection. STUDY DESIGN: Preplanned secondary analysis, intent-to-treat design for all outcomes, using Centers for Medicare & Medicaid Services (CMS) data. SETTING & PARTICIPANTS: Participants were 18 years or older and on hemodialysis therapy for more than 3 months, with Medicare as primary payor. The trial was completed at the end of 2004. INTERVENTION: Sevelamer, calcium-based phosphate binders. OUTCOMES: Mortality, morbidity, and hospitalization end points. MEASUREMENTS: DCOR subjects were linked to the CMS End-Stage Renal Disease database. Outcomes were evaluated through the CMS End-Stage Renal Disease enrollment and claims database; baseline characteristics and comorbid conditions were evaluated using CMS and case-report data. RESULTS: Groups were well balanced except for a greater percentage of calcium-group patients with atherosclerotic heart disease. Analyses were adjusted by using 10 baseline characteristics. All-cause (17.7 versus 17.4 deaths/100 patient-years; P = 0.8 unadjusted; P = 0.9 adjusted) and cardiovascular mortality (9.0 versus 8.2 deaths/100 patient-years; P = 0.3 unadjusted; P = 0.4 adjusted) did not differ significantly between treatment groups. First hospitalization, cause-specific multiple hospitalizations, first morbidity, and multiple morbidity rates also did not differ significantly. Multiple all-cause hospitalization rate (1.7 versus 1.9 admissions/patient-year; P = 0.03 unadjusted; P = 0.02 adjusted) and hospital days (12.3 versus 13.9 days/patient-year; P = 0.05 unadjusted; P = 0.03 adjusted) were lower in the sevelamer group. LIMITATIONS: Outcome parameters and cardiovascular comorbidity assessments were derived from Medicare claims data; only subjects with Medicare-as-primary-payor status were included in hospitalization and morbidity analyses. CONCLUSIONS: In this secondary analysis, treatment with sevelamer versus calcium-based binders did not affect overall mortality (primary outcome), cause-specific mortality, morbidity, or first or cause-specific hospitalization (secondary outcomes), but there was evidence for a beneficial effect on multiple all-cause hospitalizations and hospital days (secondary outcomes).

Primary study

Unclassified

Journal American journal of kidney diseases : the official journal of the National Kidney Foundation
Year 2008
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BACKGROUND: Previous clinical trials showed that progression of coronary artery calcification (CAC) may be slower in hemodialysis patients treated with sevelamer than those treated with calcium-based phosphate binders. Because sevelamer decreases low-density lipoprotein cholesterol (LDL-C) levels, we hypothesized that intensive lowering of LDL-C levels with atorvastatin in hemodialysis patients treated with calcium acetate would result in CAC progression rates similar to those in sevelamer-treated patients. STUDY DESIGN: Randomized, controlled, open-label, noninferiority trial with an upper bound for the noninferiority margin of 1.8. SETTING & PARTICIPANTS: 203 prevalent hemodialysis patients at 26 dialysis centers with serum phosphorus levels greater than 5.5 mg/dL, LDL-C levels greater than 80 mg/dL, and baseline CAC scores of 30 to 7,000 units assessed by means of electron-beam computed tomography. INTERVENTIONS: 103 patients were randomly assigned to calcium acetate, and 100 patients to sevelamer for 12 months to achieve phosphorus levels of 3.5 to 5.5 mg/dL. Atorvastatin was added to achieve serum LDL-C levels less than 70 mg/dL in both groups. OUTCOMES & MEASUREMENTS: The primary end point was change in CAC score assessed by means of electron-beam computed tomography. RESULTS: After 12 months, mean serum LDL-C levels decreased to 68.8 +/- 22.0 mg/dL in the calcium-acetate group and 62.4 +/- 23.0 mg/dL in the sevelamer group (P = 0.3). Geometric mean increases in CAC scores were 35% in the calcium-acetate group and 39% in the sevelamer group, with a covariate-adjusted calcium acetate-sevelamer ratio of 0.994 (95% confidence interval, 0.851 to 1.161). LIMITATIONS: Treatment assignment was not blinded. The 1.8 a priori margin is large, CAC is a surrogate outcome, duration of treatment was short, and dropout rate was high. CONCLUSIONS: With intensive lowering of LDL-C levels for 1 year, hemodialysis patients treated with either calcium acetate or sevelamer experienced similar progression of CAC.

Primary study

Unclassified

Authors Suki WN
Journal Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation
Year 2008
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Background: Elevated serum phosphorus and calcium are associated with arterial calcification and mortality in dialysis patients. Sevelamer, a phosphate-binding polymer, attenuates the progression of arterial calcification; it is unknown whether this improves outcomes. Patients and Interventions: A randomized comparison of sevelamer and calcium-based phosphate binders was performed in hemodialysis patients treated up to 45 months. The primary endpoint was mortality. Secondary endpoints included cause-specific mortality and hospitalization; 2103 patients were randomized, 2040 received treatment, and 1065 completed treatment. Results: Overall mortality was not significantly reduced by sevelamer (adjusted relative risk = 0.92; 95% confidence interval, 0.78 to 1.09; log-rank P = .40). Among patients ≥65 years of age, sevelamer reduced the risk of death (adjusted relative risk = 0.77; 95% confidence interval, 0.62 to 0.97; log-rank P = .02). Sevelamer patients had a trend toward fewer hospitalizations (P = .06) and fewer hospital days (P = .09). Conclusions: A statistically significant reduction in mortality in the overall study population was not observed. Sevelamer was associated with a survival benefit among patients ≥65 years of age. © 2008 National Kidney Foundation, Inc.