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Steven K Burke - One of the best experts on this subject based on the ideXlab platform.
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Sevelamer hydrochloride attenuates kidney and cardiovascular calcifications in long term experimental uremia
Kidney International, 2003Co-Authors: Mario Cozzolino, Steven K Burke, Mark E Staniforth, Helen Liapis, Jane Finch, Adriana DussoAbstract:Sevelamer hydrochloride attenuates kidney and cardiovascular calcifications in long-term experimental uremia. Background In chronic renal failure (CRF), hyperphosphatemia and an elevated calcium-phosphate product are associated with vascular calcification and increased cardiovascular morbidity and mortality. Previous data have demonstrated that 3-month treatment of uremic rats with Sevelamer was associated with less nephrocalcinosis compared to calcium carbonate (CaCO 3 ), despite similar control of serum phosphorus, calcium-phosphorus product (Ca x P product), and secondary hyperparathyroidism. There was no evidence of aortic calcification after 3 months of uremia ( J Am Soc Nephrol 13:2299–2308, 2002). The present studies explore the influence of Sevelamer and CaCO 3 on cardiovascular and kidney calcifications in long-term experimental uremia over 6 months. Methods Normal and 5/6 nephrectomized rats (U) were fed a high phosphorus (HP) diet for 6 months. Two phosphate binders, CaCO 3 and Sevelamer, were administered and their influence on hyperphosphatemia, secondary hyperparathyroidism, kidney/myocardial/aortic calcification, and renal function was compared. Results All uremic rats began the study with the same degree of renal failure. Sevelamer was as effective as CaCO 3 in reducing serum phosphorus, Ca x P product, and attenuating secondary hyperparathyroidism. Despite similar serum cholesterol levels, rats in the U-HP + Sevelamer group had markedly lower calcium deposition in the myocardium and aorta (myocardium, 72 ± 4 μg/g wet tissue; aorta, 736 ± 156 μg/g wet tissue) compared to rats in either the U-HP + CaCO 3 group (myocardium, 179 ± 48, P P P 3 (1196 ± 180 μg/g wet tissue). Sevelamer-treated rats had less deterioration in renal function with an associated lower serum creatinine, higher creatinine clearance, and less proteinuria. There was no difference in overall mortality between the three experimental groups. Conclusion In long-term experimental CRF, in addition to controlling serum phosphorus and secondary hyperparathyroidism as efficiently as CaCO 3 , treatment with the phosphate-binder Sevelamer attenuates vascular and kidney calcification.
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Sevelamer hydrochloride a phosphate binder protects against deterioration of renal function in rats with progressive chronic renal insufficiency
Nephrology Dialysis Transplantation, 2003Co-Authors: Nobuo Nagano, Steven K Burke, Sonoe Miyata, Nami Kobayashi, Sachiko Obana, Naoshi Fukushima, Michihito WadaAbstract:BACKGROUND: Dietary phosphate restriction prevents renal function deterioration in animal models. This study examined whether Sevelamer hydrochloride (Renagel(R); 'Sevelamer' hereafter), a non-calcaemic phosphate binder could slow deterioration of renal function in rats with progressive renal insufficiency. METHODS: Wistar Kyoto male rats were singly injected with normal rabbit serum or rabbit anti-rat glomerular basement membrane serum. Three days later, rats were fed a powder diet containing 0, 1 or 3% Sevelamer for 58 days. Time course changes of serum levels of blood urea nitrogen (BUN), creatinine, calcium, phosphorus and parathyroid hormone (PTH) were measured throughout, and creatinine clearance (CCr), kidney calcium content and renal histology examined at the end of the study. RESULTS: Sevelamer partially inhibited elevation of BUN and serum creatinine, and completely inhibited increases in serum phosphorus, PTH and calcium xphosphorus product. Sevelamer significantly prevented the decrease in CCr and kidney calcium content elevation. Kidney calcium content and BUN and serum creatinine were strongly positively correlated, and kidney calcium content and CCr strongly negatively correlated. Kidney calcium content correlated well with serum phosphorus, serum calcium x phosphorus product and PTH, but not serum calcium. Sevelamer treatment partly prevented histological deterioration of both glomerular and tubulointerstitial lesions of the kidney. CONCLUSIONS: The results suggest that Sevelamer protects against renal function deterioration by maintaining kidney calcium at a low level as a result of reducing serum phosphorus and PTH.
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Sevelamer hydrochloride prevents ectopic calcification and renal osteodystrophy in chronic renal failure rats
Kidney International, 2003Co-Authors: Kyoko Katsumata, Steven K Burke, Nobuo Nagano, Kenichiro Kusano, Michinori Hirata, Kunihiko Tsunemi, Naoshi FukushimaAbstract:Sevelamer hydrochloride prevents ectopic calcification and renal osteodystrophy in chronic renal failure rats. Background Hyperphosphatemia is associated with severe complications, including ectopic calcification of soft tissues, secondary hyperparathyroidism, and renal osteodystrophy (ROD). Sevelamer hydrochloride is a nonabsorbed calcium- and metal-free phosphate binder that lowers serum phosphorus levels in hemodialysis patients. This study examined the efficacy of Sevelamer in preventing ectopic calcification of soft tissues and ROD in adenine-induced renal failure rats. Methods Male, 12-week-old Wistar-Jcl rats were freely fed an adenine diet (0.75g adenine in 100g normal diet) for four weeks. After three weeks of the adenine diet, when serum phosphorus levels had significantly increased, the rats were freely fed a normal diet that contained 1% or 2% of Sevelamer for another five weeks. Time course changes of serum levels of phosphorus, calcium, and parathyroid hormone (PTH) were measured. At the end of the study, calcium and phosphorus levels in the heart and aorta were measured, and the calcification of kidney, heart, aorta, and stomach were histopathologically examined. The severity of ROD was evaluated by a histopathologic and morphometric analysis of the femurs. Results Compared with the adenine controls ( N = 10), the Sevelamer-treated (1%, N = 6; and 2%, N = 10) groups of adenine-induced renal failure rats had reduced serum phosphorus, serum calcium × phosphorus product, and serum PTH levels. Moreover, in the treatment groups, Sevelamer suppressed calcification of the aorta media, and also the osteoid volume, fibrosis volume, and porosity ratio of femurs. Conclusion These results suggest that Sevelamer treatment might contribute to the suppression of ectopic calcification and ROD.
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Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients
Kidney International, 2002Co-Authors: Steven K Burke, Paolo Raggi, Glenn M ChertowAbstract:Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Background Cardiovascular disease is frequent and severe in patients with end-stage renal disease. Disorders of mineral metabolism may contribute by promoting cardiovascular calcification. Methods We conducted a randomized clinical trial comparing Sevelamer, a non-absorbed polymer, with calcium-based phosphate binders in 200 hemodialysis patients. Study outcomes included the targeted concentrations of serum phosphorus, calcium, and intact parathyroid hormone (PTH), and calcification of the coronary arteries and thoracic aorta using a calcification score derived from electron beam tomography. Results Sevelamer and calcium provided equivalent control of serum phosphorus (end-of-study values 5.1 ± 1.2 and 5.1 ± 1.4 mg/dL, respectively, P = 0.33). Serum calcium concentration was significantly higher in the calcium-treated group ( P = 0.002), and hypercalcemia was more common (16% vs. 5% with Sevelamer, P = 0.04). More subjects in the calcium group had end-of-study intact PTH below the target of 150 to 300 pg/mL (57% vs. 30%, P = 0.001). At study completion, the median absolute calcium score in the coronary arteries and aorta increased significantly in the calcium treated subjects but not in the Sevelamer-treated subjects (coronary arteries 36.6 vs. 0, P = 0.03 and aorta 75.1 vs. 0, P = 0.01, respectively). The median percent change in coronary artery (25% vs. 6%, P = 0.02) and aortic (28% vs. 5%, P = 0.02) calcium score also was significantly greater with calcium than with Sevelamer. Conclusions Compared with calcium-based phosphate binders, Sevelamer is less likely to cause hypercalcemia, low levels of PTH, and progressive coronary and aortic calcification in hemodialysis patients.
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Sevelamer hydrochloride renagel a non calcaemic phosphate binder arrests parathyroid gland hyperplasia in rats with progressive chronic renal insufficiency
Nephrology Dialysis Transplantation, 2001Co-Authors: Nobuo Nagano, Steven K Burke, Sonoe Miyata, Nami Kobayashi, Sachiko Obana, Naoshi Fukushima, Masako Ozai, Michihito WadaAbstract:BACKGROUND: It has been demonstrated that dietary phosphate restriction suppresses parathyroid hormone (PTH) secretion and parathyroid cell proliferation in experimental animals with chronic renal insufficiency (CRI) independently of serum calcium and 1,25(OH)(2)D3 levels. This study was conducted to examine whether Sevelamer hydrochloride (Renagel); hereafter referred to as Sevelamer), a non-calcaemic phosphate binder could inhibit the parathyroid gland (PTG) hyperplasia in rats with progressive CRI. METHODS: Male Sprague-Dawley rats were injected twice with low doses of adriamycin (ADR). Two weeks after the last injection of ADR, rats were fed a diet containing 1 or 3% Sevelamer for 84 days. Time course changes of serum levels of calcium, phosphorus, and PTH were measured. At the end of study, serum 1,25(OH)(2)D3 levels were measured and the maximal two-dimension area of the PTG in paraffin section was calculated using an imaging analyser. RESULTS: Dietary Sevelamer treatment inhibited the elevations of serum phosphorus, calciumxphosphorus product, and PTH levels that occurred as the study progressed. Sevelamer also suppressed maximal PTG area and there existed positive strong correlation between maximal PTG area and serum PTH levels at the end of the study. Serum phosphorus levels positively correlated well with serum PTH levels and maximal PTG area. In contrast, serum calcium or 1,25(OH)(2)D3 levels did not show any correlation with serum PTH levels and maximal PTG area. CONCLUSIONS: Sevelamer treatment arrested hyperphosphataemia and PTG hyperplasia accompanied by the elevation of serum PTH levels. The correlation analysis suggests that reduced serum phosphorus levels contributed to the suppression of PTG hyperplasia and resulted in the reduction of PTH levels in this animal model after the Sevelamer treatment. The management of phosphorus control started from early stage of CRI could prevent PTG hyperplasia and facilitate later management of secondary hyperparathyroidism.
Jürgen Floege - One of the best experts on this subject based on the ideXlab platform.
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effects of sucroferric oxyhydroxide and Sevelamer carbonate on chronic kidney disease mineral bone disorder parameters in dialysis patients
Nephrology Dialysis Transplantation, 2019Co-Authors: Markus Ketteler, Viatcheslav Rakov, Anjay Rastogi, Bruce Spinowitz, Stuart M Sprague, Adrian Covic, Sebastian Walpen, Jürgen FloegeAbstract:BACKGROUND Treatment of hyperphosphataemia is the primary goal of chronic kidney disease-mineral and bone disorder (CKD-MBD) management. This post hoc analysis of a randomized, Phase 3 study evaluated the effects of 1-year treatment with the phosphate binders sucroferric oxyhydroxide or Sevelamer carbonate ('Sevelamer') on CKD-MBD indices among dialysis patients with hyperphosphataemia. METHODS After a 2- to 4-week washout from previous phosphate binders, 1059 patients were randomized 2:1 to sucroferric oxyhydroxide 1.0-3.0 g/day (n = 710) or Sevelamer 2.4-14.4 g/day (n = 349) for up to 24 weeks. Eligible patients enrolled in a 28-week extension. This post hoc analysis was performed for patients who completed ≥1 year of continuous treatment (n = 549). As the treatment groups showed similar CKD-MBD outcomes, the data were pooled for this analysis. RESULTS Phosphate-binder therapy was associated with significant and sustained 30% reductions in serum phosphorus (P < 0.001). Median intact fibroblast growth factor-23 (FGF-23) also significantly decreased (P < 0.001) by 64% over 1 year. Intact parathyroid hormone decreased significantly after 24 weeks (P < 0.001), but levels returned to near baseline values by Week 52; minimal changes in serum calcium were observed. Of the bone resorption markers evaluated, tartrate-resistant acid phosphatase 5b (TRAP5b) decreased significantly (P < 0.001), whereas CTx increased transiently but returned to baseline levels by Week 52. The bone formation markers bone-specific alkaline phosphatase and osteocalcin both increased over 1 year of treatment. CONCLUSIONS Overall, 1 year of sucroferric oxyhydroxide or Sevelamer treatment significantly reduced serum FGF-23, which has been associated with clinical benefit in patients with CKD. The trend towards increased bone formation marker levels indicates a beneficial effect on bone metabolism.
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one year efficacy and safety of the iron based phosphate binder sucroferric oxyhydroxide in patients on peritoneal dialysis
Nephrology Dialysis Transplantation, 2017Co-Authors: Jürgen Floege, Viatcheslav Rakov, Anjay Rastogi, Bruce Spinowitz, Laura J Lisk, Johannes F.e. Mann, Markus Ketteler, Adrian Covic, Stuart M SpragueAbstract:Background: Sucroferric oxyhydroxide is a noncalcium, iron-based phosphate binder that demonstrated sustained serum phosphorus control, good tolerability and lower pill burden compared with Sevelamer carbonate (Sevelamer) in a Phase 3 study conducted in dialysis patients. This subanalysis examines the efficacy and tolerability of sucroferric oxyhydroxide and Sevelamer in the peritoneal dialysis (PD) patient population. Methods: The initial study (NCT01324128) and its extension (NCT01464190) were multicenter, Phase 3, open-label, randomized (2:1), active-controlled trials comparing sucroferric oxyhydroxide (1.0-3.0 g/day) with Sevelamer (2.4-14.4 g/day) in dialysis patients over 52 weeks in total. Results: In the overall study, 84/1055 (8.1%) patients received PD and were eligible for efficacy analysis (sucroferric oxyhydroxide, n = 56; Sevelamer, n = 28). The two groups were broadly comparable to each other and to the overall study population. Serum phosphorus concentrations decreased comparably with both phosphate binders by week 12 (mean change from baseline - 0.6 mmol/L). Over 52 weeks, sucroferric oxyhydroxide effectively reduced serum phosphorus concentrations to a similar extent as Sevelamer; 62.5% and 64.3% of patients, respectively, were below the Kidney Disease Outcomes Quality Initiative target range (≤1.78 mmol/L). This was achieved with a lower pill burden (3.4 ± 1.3 versus 8.1 ± 3.7 tablets/day) with sucroferric oxyhydroxide compared with Sevelamer. Treatment adherence rates were 91.2% with sucroferric oxyhydroxide and 79.3% with Sevelamer. The proportion of patients reporting at least one treatment-emergent adverse event was 86.0% with sucroferric oxyhydroxide and 93.1% with Sevelamer. The most common adverse events with both treatments were gastrointestinal: diarrhea and discolored feces with sucroferric oxyhydroxide and nausea, vomiting and constipation with Sevelamer. Conclusions: Sucroferric oxyhydroxide is noninferior to Sevelamer for controlling serum phosphorus in patients undergoing PD, while providing a relatively low pill burden and a high rate of adherence.
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long term effects of the iron based phosphate binder sucroferric oxyhydroxide in dialysis patients
Nephrology Dialysis Transplantation, 2015Co-Authors: Jürgen Floege, Sylvain Gaillard, Anjay Rastogi, Bruce Spinowitz, Edward M F Chong, Laura J Lisk, Johannes F.e. Mann, Markus Ketteler, Adrian Covic, Stuart M SpragueAbstract:Background. Hyperphosphatemia necessitates the use of phosphate binders in most dialysis patients. Long-term efficacy and tolerability of the iron-based phosphate binder, sucroferric oxyhydroxide (previously known as PA21), was compared with that of Sevelamer carbonate (Sevelamer) in an open-label Phase III extension study. Methods. In the initial Phase III study, hemo- or peritoneal dialysis patients with hyperphosphatemia were randomized 2:1 to receive sucroferric oxyhydroxide 1.0−3.0 g/day (2−6 tablets/day; n = 710) or Sevelamer 2.4−14.4 g/day (3−18 tablets/day; n = 349) for 24 weeks. Eligible patients could enter the 28-week extension study, continuing the same treatment and dose they were receiving at the end of the initial study. Results. Overall, 644 patients were available for efficacy analysis (n = 384 sucroferric oxyhydroxide; n= 260 Sevelamer). Serum phosphorus concentrations were maintained during the extension study. Mean ± standard deviation (SD) change in serum phosphorus concentrations from extension study baseline to Week 52 end point was 0.02±0.52 mmol/L with sucroferric oxyhydroxide and 0.09±0.58 mmol/L with Sevelamer. Mean serum phosphorus concentrations remained within Kidney Disease Outcomes Quality Initiative target range (1.13– 1.78 mmol/L) for both treatment groups. Mean (SD) daily tablet number over the 28-week extension study was lower for
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a phase iii study of the efficacy and safety of a novel iron based phosphate binder in dialysis patients
Kidney International, 2014Co-Authors: Jürgen Floege, Sylvain Gaillard, Anjay Rastogi, Edward M F Chong, Laura J Lisk, Markus Ketteler, Adrian Covic, Stuart M SpragueAbstract:Efficacy of PA21 (sucroferric oxyhydroxide), a novel calcium-free polynuclear iron(III)-oxyhydroxide phosphate binder, was compared with that of Sevelamer carbonate in an open-label, randomized, active-controlled phase III study. Seven hundred and seven hemo- and peritoneal dialysis patients with hyperphosphatemia received PA21 1.0–3.0g per day and 348 received Sevelamer 4.8–14.4g per day for an 8-week dose titration, followed by 4 weeks without dose change, and then 12 weeks maintenance. Serum phosphorus reductions at week 12 were -0.71mmol/l (PA21) and -0.79mmol/l (Sevelamer), demonstrating non-inferiority of, on average, three tablets of PA21 vs. eight of Sevelamer. Efficacy was maintained to week 24. Non-adherence was 15.1% (PA21) vs. 21.3% (Sevelamer). The percentage of patients that reported at least one treatment-emergent adverse event was 83.2% with PA21 and 76.1% with Sevelamer. A higher proportion of patients withdrew owing to treatment-emergent adverse events with PA21 (15.7%) vs. Sevelamer (6.6%). Mild, transient diarrhea, discolored feces, and hyperphosphatemia were more frequent with PA21; nausea and constipation were more frequent with Sevelamer. After 24 weeks, 99 hemodialysis patients on PA21 were re-randomized into a 3-week superiority analysis of PA21 maintenance dose in 50 patients vs. low dose (250mg per day (ineffective control)) in 49 patients. The PA21 maintenance dose was superior to the low dose in maintaining serum phosphorus control. Thus, PA21 was effective in lowering serum phosphorus in dialysis patients, with similar efficacy to Sevelamer carbonate, a lower pill burden, and better adherence.
Isidro B. Salusky - One of the best experts on this subject based on the ideXlab platform.
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phosphate binders vitamin d and calcimimetics in the management of chronic kidney disease mineral bone disorders ckd mbd in children
Pediatric Nephrology, 2013Co-Authors: Katherine Wesselingperry, Isidro B. SaluskyAbstract:In order to minimize complications on the skeleton and to prevent extraskeletal calcifications, the specific aims of the management of chronic kidney disease mineral and bone disorder (CKD-MBD) are to maintain blood levels of serum calcium and phosphorus as close to the normal range as possible, thereby maintaining serum parathyroid hormone (PTH) at levels appropriate for CKD stage, preventing hyperplasia of the parathyroid glands, avoiding the development of extra-skeletal calcifications, and preventing or reversing the accumulation of toxic substances such as aluminum and β2-microglobulin. In order to limit cardiovascular calcification, daily intake of elemental calcium, including from dietary sources and from phosphate binders, should not exceed twice the daily recommended intake for age and should not exceed 2.5 g/day. Calcium-free phosphate binders, such as Sevelamer hydrochloride and Sevelamer carbonate, are safe and effective alternatives to calcium-based binders, and their use widens the margin of safety for active vitamin D sterol therapy. Vitamin D deficiency is highly prevalent across the spectrum of CKD, and replacement therapy is recommended in vitamin D-deficient and insufficient individuals. Therapy with active vitamin D sterols is recommended after correction of the vitamin D deficiency state and should be titrated based on target PTH levels across the spectrum of CKD. Although the use of calcimimetic drugs has been proven to effectively control the biochemical features of secondary hyperparathyroidism, there is very limited experience with the use of such agents in pediatric patients and especially during the first years of life. Studies are needed to further define the role of such agents in the treatment of pediatric CKD-MBD.
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calcitriol and doxercalciferol are equivalent in controlling bone turnover suppressing parathyroid hormone and increasing fibroblast growth factor 23 in secondary hyperparathyroidism
Kidney International, 2011Co-Authors: Katherine Wesselingperry, Barbara Gales, Hejing Wang, Robert Elashoff, Renata C Pereira, Shobha Sahney, Harald Juppner, Isidro B. SaluskyAbstract:We compared the effects of calcitriol and doxercalciferol, in combination with either calcium carbonate or Sevelamer, on bone, mineral, and fibroblast growth factor-23 (FGF-23) metabolism in patients with secondary hyperparathyroidism. A total of 60 pediatric patients treated with peritoneal dialysis were randomized to 8 months of therapy with either oral calcitriol or doxercalciferol, combined with either calcium carbonate or Sevelamer. Bone formation rates decreased during therapy and final values were within the normal range in 72% of patients. A greater improvement in eroded surface was found in patients treated with doxercalciferol than in those given calcitriol. On initial bone biopsy, a mineralization defect was identified in the majority of patients which did not normalize with therapy. Serum phosphate concentrations were controlled equally well by both binders, but serum calcium levels increased during treatment with calcium carbonate, and serum parathyroid hormone levels were decreased by 35% in all groups. Baseline plasma FGF-23 values were significantly elevated and rose over fourfold with calcitriol and doxercalciferol, irrespective of phosphate binder. Thus, doxercalciferol is as effective as calcitriol in controlling serum parathyroid hormone levels and suppressing the bone formation rate. Sevelamer allows the use of higher doses of vitamin D. Implications of these changes on bone and cardiovascular biology remain to be established.
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Sevelamer hydrochloride an effective phosphate binder in dialyzed children
Pediatric Nephrology, 2003Co-Authors: Homa Mahdavi, Barbara Gales, Beatriz D Kuizon, Hejing Wang, Robert Elashoff, Isidro B. SaluskyAbstract:This pilot study was designed to evaluate the efficacy and acceptability of Sevelamer hydrochloride as a phosphate binder in pediatric patients treated with dialysis. A 6-month open-label trial of Sevelamer hydrochloride (Renagel) was initiated in 17 patients, aged 11.8±3.7 years, undergoing hemodialysis (n=3) or peritoneal dialysis (n=14). Following a 2-week washout period of the phosphate binders, serum phosphorus increased from 5.2±1.3 mg/dl to 7.5±2.2 mg/dl (P<0.0002). After initiation of therapy with Sevelamer hydrochloride, serum phosphorus levels decreased to 6.2±1.2 mg/dl (P<0.01) during the first 8 weeks and final values were 6.3±1.5 mg/dl. Serum calcium concentration decreased during the washout period from 9.4±0.9 mg/dl to 8.9±1.5 mg/dl (P<0.01); values remained unchanged thereafter. The serum calcium-phosphorus ion product decreased during the first 8 weeks and values did not change subsequently. Serum bicarbonate, parathyroid hormone, total cholesterol, low-density lipoprotein and high-density lipoprotein cholesterol, and triglyceride levels did not change. The initial prescribed dose of Sevelamer hydrochloride was 121±50 mg/kg (4.5±5 g/day) and the final prescribed dose was 163±46 mg/kg (6.7±2.4 g/day). Sevelamer hydrochloride was well tolerated and without adverse effects related to the drug.
Markus Ketteler - One of the best experts on this subject based on the ideXlab platform.
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effects of sucroferric oxyhydroxide and Sevelamer carbonate on chronic kidney disease mineral bone disorder parameters in dialysis patients
Nephrology Dialysis Transplantation, 2019Co-Authors: Markus Ketteler, Viatcheslav Rakov, Anjay Rastogi, Bruce Spinowitz, Stuart M Sprague, Adrian Covic, Sebastian Walpen, Jürgen FloegeAbstract:BACKGROUND Treatment of hyperphosphataemia is the primary goal of chronic kidney disease-mineral and bone disorder (CKD-MBD) management. This post hoc analysis of a randomized, Phase 3 study evaluated the effects of 1-year treatment with the phosphate binders sucroferric oxyhydroxide or Sevelamer carbonate ('Sevelamer') on CKD-MBD indices among dialysis patients with hyperphosphataemia. METHODS After a 2- to 4-week washout from previous phosphate binders, 1059 patients were randomized 2:1 to sucroferric oxyhydroxide 1.0-3.0 g/day (n = 710) or Sevelamer 2.4-14.4 g/day (n = 349) for up to 24 weeks. Eligible patients enrolled in a 28-week extension. This post hoc analysis was performed for patients who completed ≥1 year of continuous treatment (n = 549). As the treatment groups showed similar CKD-MBD outcomes, the data were pooled for this analysis. RESULTS Phosphate-binder therapy was associated with significant and sustained 30% reductions in serum phosphorus (P < 0.001). Median intact fibroblast growth factor-23 (FGF-23) also significantly decreased (P < 0.001) by 64% over 1 year. Intact parathyroid hormone decreased significantly after 24 weeks (P < 0.001), but levels returned to near baseline values by Week 52; minimal changes in serum calcium were observed. Of the bone resorption markers evaluated, tartrate-resistant acid phosphatase 5b (TRAP5b) decreased significantly (P < 0.001), whereas CTx increased transiently but returned to baseline levels by Week 52. The bone formation markers bone-specific alkaline phosphatase and osteocalcin both increased over 1 year of treatment. CONCLUSIONS Overall, 1 year of sucroferric oxyhydroxide or Sevelamer treatment significantly reduced serum FGF-23, which has been associated with clinical benefit in patients with CKD. The trend towards increased bone formation marker levels indicates a beneficial effect on bone metabolism.
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one year efficacy and safety of the iron based phosphate binder sucroferric oxyhydroxide in patients on peritoneal dialysis
Nephrology Dialysis Transplantation, 2017Co-Authors: Jürgen Floege, Viatcheslav Rakov, Anjay Rastogi, Bruce Spinowitz, Laura J Lisk, Johannes F.e. Mann, Markus Ketteler, Adrian Covic, Stuart M SpragueAbstract:Background: Sucroferric oxyhydroxide is a noncalcium, iron-based phosphate binder that demonstrated sustained serum phosphorus control, good tolerability and lower pill burden compared with Sevelamer carbonate (Sevelamer) in a Phase 3 study conducted in dialysis patients. This subanalysis examines the efficacy and tolerability of sucroferric oxyhydroxide and Sevelamer in the peritoneal dialysis (PD) patient population. Methods: The initial study (NCT01324128) and its extension (NCT01464190) were multicenter, Phase 3, open-label, randomized (2:1), active-controlled trials comparing sucroferric oxyhydroxide (1.0-3.0 g/day) with Sevelamer (2.4-14.4 g/day) in dialysis patients over 52 weeks in total. Results: In the overall study, 84/1055 (8.1%) patients received PD and were eligible for efficacy analysis (sucroferric oxyhydroxide, n = 56; Sevelamer, n = 28). The two groups were broadly comparable to each other and to the overall study population. Serum phosphorus concentrations decreased comparably with both phosphate binders by week 12 (mean change from baseline - 0.6 mmol/L). Over 52 weeks, sucroferric oxyhydroxide effectively reduced serum phosphorus concentrations to a similar extent as Sevelamer; 62.5% and 64.3% of patients, respectively, were below the Kidney Disease Outcomes Quality Initiative target range (≤1.78 mmol/L). This was achieved with a lower pill burden (3.4 ± 1.3 versus 8.1 ± 3.7 tablets/day) with sucroferric oxyhydroxide compared with Sevelamer. Treatment adherence rates were 91.2% with sucroferric oxyhydroxide and 79.3% with Sevelamer. The proportion of patients reporting at least one treatment-emergent adverse event was 86.0% with sucroferric oxyhydroxide and 93.1% with Sevelamer. The most common adverse events with both treatments were gastrointestinal: diarrhea and discolored feces with sucroferric oxyhydroxide and nausea, vomiting and constipation with Sevelamer. Conclusions: Sucroferric oxyhydroxide is noninferior to Sevelamer for controlling serum phosphorus in patients undergoing PD, while providing a relatively low pill burden and a high rate of adherence.
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long term effects of the iron based phosphate binder sucroferric oxyhydroxide in dialysis patients
Nephrology Dialysis Transplantation, 2015Co-Authors: Jürgen Floege, Sylvain Gaillard, Anjay Rastogi, Bruce Spinowitz, Edward M F Chong, Laura J Lisk, Johannes F.e. Mann, Markus Ketteler, Adrian Covic, Stuart M SpragueAbstract:Background. Hyperphosphatemia necessitates the use of phosphate binders in most dialysis patients. Long-term efficacy and tolerability of the iron-based phosphate binder, sucroferric oxyhydroxide (previously known as PA21), was compared with that of Sevelamer carbonate (Sevelamer) in an open-label Phase III extension study. Methods. In the initial Phase III study, hemo- or peritoneal dialysis patients with hyperphosphatemia were randomized 2:1 to receive sucroferric oxyhydroxide 1.0−3.0 g/day (2−6 tablets/day; n = 710) or Sevelamer 2.4−14.4 g/day (3−18 tablets/day; n = 349) for 24 weeks. Eligible patients could enter the 28-week extension study, continuing the same treatment and dose they were receiving at the end of the initial study. Results. Overall, 644 patients were available for efficacy analysis (n = 384 sucroferric oxyhydroxide; n= 260 Sevelamer). Serum phosphorus concentrations were maintained during the extension study. Mean ± standard deviation (SD) change in serum phosphorus concentrations from extension study baseline to Week 52 end point was 0.02±0.52 mmol/L with sucroferric oxyhydroxide and 0.09±0.58 mmol/L with Sevelamer. Mean serum phosphorus concentrations remained within Kidney Disease Outcomes Quality Initiative target range (1.13– 1.78 mmol/L) for both treatment groups. Mean (SD) daily tablet number over the 28-week extension study was lower for
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a phase iii study of the efficacy and safety of a novel iron based phosphate binder in dialysis patients
Kidney International, 2014Co-Authors: Jürgen Floege, Sylvain Gaillard, Anjay Rastogi, Edward M F Chong, Laura J Lisk, Markus Ketteler, Adrian Covic, Stuart M SpragueAbstract:Efficacy of PA21 (sucroferric oxyhydroxide), a novel calcium-free polynuclear iron(III)-oxyhydroxide phosphate binder, was compared with that of Sevelamer carbonate in an open-label, randomized, active-controlled phase III study. Seven hundred and seven hemo- and peritoneal dialysis patients with hyperphosphatemia received PA21 1.0–3.0g per day and 348 received Sevelamer 4.8–14.4g per day for an 8-week dose titration, followed by 4 weeks without dose change, and then 12 weeks maintenance. Serum phosphorus reductions at week 12 were -0.71mmol/l (PA21) and -0.79mmol/l (Sevelamer), demonstrating non-inferiority of, on average, three tablets of PA21 vs. eight of Sevelamer. Efficacy was maintained to week 24. Non-adherence was 15.1% (PA21) vs. 21.3% (Sevelamer). The percentage of patients that reported at least one treatment-emergent adverse event was 83.2% with PA21 and 76.1% with Sevelamer. A higher proportion of patients withdrew owing to treatment-emergent adverse events with PA21 (15.7%) vs. Sevelamer (6.6%). Mild, transient diarrhea, discolored feces, and hyperphosphatemia were more frequent with PA21; nausea and constipation were more frequent with Sevelamer. After 24 weeks, 99 hemodialysis patients on PA21 were re-randomized into a 3-week superiority analysis of PA21 maintenance dose in 50 patients vs. low dose (250mg per day (ineffective control)) in 49 patients. The PA21 maintenance dose was superior to the low dose in maintaining serum phosphorus control. Thus, PA21 was effective in lowering serum phosphorus in dialysis patients, with similar efficacy to Sevelamer carbonate, a lower pill burden, and better adherence.
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evaluation of calcium acetate magnesium carbonate as a phosphate binder compared with Sevelamer hydrochloride in haemodialysis patients a controlled randomized study calmag study assessing efficacy and tolerability
Nephrology Dialysis Transplantation, 2010Co-Authors: Angel L M De Francisco, Michael Leidig, Ewa Benedyklorens, Gabriel Mircescu, Caecilia Scholz, Pedro Ponce, Markus Ketteler, Adrian Covic, Jutta PasslickdeetjenAbstract: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.
Stuart M Sprague - One of the best experts on this subject based on the ideXlab platform.
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effects of sucroferric oxyhydroxide and Sevelamer carbonate on chronic kidney disease mineral bone disorder parameters in dialysis patients
Nephrology Dialysis Transplantation, 2019Co-Authors: Markus Ketteler, Viatcheslav Rakov, Anjay Rastogi, Bruce Spinowitz, Stuart M Sprague, Adrian Covic, Sebastian Walpen, Jürgen FloegeAbstract:BACKGROUND Treatment of hyperphosphataemia is the primary goal of chronic kidney disease-mineral and bone disorder (CKD-MBD) management. This post hoc analysis of a randomized, Phase 3 study evaluated the effects of 1-year treatment with the phosphate binders sucroferric oxyhydroxide or Sevelamer carbonate ('Sevelamer') on CKD-MBD indices among dialysis patients with hyperphosphataemia. METHODS After a 2- to 4-week washout from previous phosphate binders, 1059 patients were randomized 2:1 to sucroferric oxyhydroxide 1.0-3.0 g/day (n = 710) or Sevelamer 2.4-14.4 g/day (n = 349) for up to 24 weeks. Eligible patients enrolled in a 28-week extension. This post hoc analysis was performed for patients who completed ≥1 year of continuous treatment (n = 549). As the treatment groups showed similar CKD-MBD outcomes, the data were pooled for this analysis. RESULTS Phosphate-binder therapy was associated with significant and sustained 30% reductions in serum phosphorus (P < 0.001). Median intact fibroblast growth factor-23 (FGF-23) also significantly decreased (P < 0.001) by 64% over 1 year. Intact parathyroid hormone decreased significantly after 24 weeks (P < 0.001), but levels returned to near baseline values by Week 52; minimal changes in serum calcium were observed. Of the bone resorption markers evaluated, tartrate-resistant acid phosphatase 5b (TRAP5b) decreased significantly (P < 0.001), whereas CTx increased transiently but returned to baseline levels by Week 52. The bone formation markers bone-specific alkaline phosphatase and osteocalcin both increased over 1 year of treatment. CONCLUSIONS Overall, 1 year of sucroferric oxyhydroxide or Sevelamer treatment significantly reduced serum FGF-23, which has been associated with clinical benefit in patients with CKD. The trend towards increased bone formation marker levels indicates a beneficial effect on bone metabolism.
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one year efficacy and safety of the iron based phosphate binder sucroferric oxyhydroxide in patients on peritoneal dialysis
Nephrology Dialysis Transplantation, 2017Co-Authors: Jürgen Floege, Viatcheslav Rakov, Anjay Rastogi, Bruce Spinowitz, Laura J Lisk, Johannes F.e. Mann, Markus Ketteler, Adrian Covic, Stuart M SpragueAbstract:Background: Sucroferric oxyhydroxide is a noncalcium, iron-based phosphate binder that demonstrated sustained serum phosphorus control, good tolerability and lower pill burden compared with Sevelamer carbonate (Sevelamer) in a Phase 3 study conducted in dialysis patients. This subanalysis examines the efficacy and tolerability of sucroferric oxyhydroxide and Sevelamer in the peritoneal dialysis (PD) patient population. Methods: The initial study (NCT01324128) and its extension (NCT01464190) were multicenter, Phase 3, open-label, randomized (2:1), active-controlled trials comparing sucroferric oxyhydroxide (1.0-3.0 g/day) with Sevelamer (2.4-14.4 g/day) in dialysis patients over 52 weeks in total. Results: In the overall study, 84/1055 (8.1%) patients received PD and were eligible for efficacy analysis (sucroferric oxyhydroxide, n = 56; Sevelamer, n = 28). The two groups were broadly comparable to each other and to the overall study population. Serum phosphorus concentrations decreased comparably with both phosphate binders by week 12 (mean change from baseline - 0.6 mmol/L). Over 52 weeks, sucroferric oxyhydroxide effectively reduced serum phosphorus concentrations to a similar extent as Sevelamer; 62.5% and 64.3% of patients, respectively, were below the Kidney Disease Outcomes Quality Initiative target range (≤1.78 mmol/L). This was achieved with a lower pill burden (3.4 ± 1.3 versus 8.1 ± 3.7 tablets/day) with sucroferric oxyhydroxide compared with Sevelamer. Treatment adherence rates were 91.2% with sucroferric oxyhydroxide and 79.3% with Sevelamer. The proportion of patients reporting at least one treatment-emergent adverse event was 86.0% with sucroferric oxyhydroxide and 93.1% with Sevelamer. The most common adverse events with both treatments were gastrointestinal: diarrhea and discolored feces with sucroferric oxyhydroxide and nausea, vomiting and constipation with Sevelamer. Conclusions: Sucroferric oxyhydroxide is noninferior to Sevelamer for controlling serum phosphorus in patients undergoing PD, while providing a relatively low pill burden and a high rate of adherence.
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long term effects of the iron based phosphate binder sucroferric oxyhydroxide in dialysis patients
Nephrology Dialysis Transplantation, 2015Co-Authors: Jürgen Floege, Sylvain Gaillard, Anjay Rastogi, Bruce Spinowitz, Edward M F Chong, Laura J Lisk, Johannes F.e. Mann, Markus Ketteler, Adrian Covic, Stuart M SpragueAbstract:Background. Hyperphosphatemia necessitates the use of phosphate binders in most dialysis patients. Long-term efficacy and tolerability of the iron-based phosphate binder, sucroferric oxyhydroxide (previously known as PA21), was compared with that of Sevelamer carbonate (Sevelamer) in an open-label Phase III extension study. Methods. In the initial Phase III study, hemo- or peritoneal dialysis patients with hyperphosphatemia were randomized 2:1 to receive sucroferric oxyhydroxide 1.0−3.0 g/day (2−6 tablets/day; n = 710) or Sevelamer 2.4−14.4 g/day (3−18 tablets/day; n = 349) for 24 weeks. Eligible patients could enter the 28-week extension study, continuing the same treatment and dose they were receiving at the end of the initial study. Results. Overall, 644 patients were available for efficacy analysis (n = 384 sucroferric oxyhydroxide; n= 260 Sevelamer). Serum phosphorus concentrations were maintained during the extension study. Mean ± standard deviation (SD) change in serum phosphorus concentrations from extension study baseline to Week 52 end point was 0.02±0.52 mmol/L with sucroferric oxyhydroxide and 0.09±0.58 mmol/L with Sevelamer. Mean serum phosphorus concentrations remained within Kidney Disease Outcomes Quality Initiative target range (1.13– 1.78 mmol/L) for both treatment groups. Mean (SD) daily tablet number over the 28-week extension study was lower for
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a phase iii study of the efficacy and safety of a novel iron based phosphate binder in dialysis patients
Kidney International, 2014Co-Authors: Jürgen Floege, Sylvain Gaillard, Anjay Rastogi, Edward M F Chong, Laura J Lisk, Markus Ketteler, Adrian Covic, Stuart M SpragueAbstract:Efficacy of PA21 (sucroferric oxyhydroxide), a novel calcium-free polynuclear iron(III)-oxyhydroxide phosphate binder, was compared with that of Sevelamer carbonate in an open-label, randomized, active-controlled phase III study. Seven hundred and seven hemo- and peritoneal dialysis patients with hyperphosphatemia received PA21 1.0–3.0g per day and 348 received Sevelamer 4.8–14.4g per day for an 8-week dose titration, followed by 4 weeks without dose change, and then 12 weeks maintenance. Serum phosphorus reductions at week 12 were -0.71mmol/l (PA21) and -0.79mmol/l (Sevelamer), demonstrating non-inferiority of, on average, three tablets of PA21 vs. eight of Sevelamer. Efficacy was maintained to week 24. Non-adherence was 15.1% (PA21) vs. 21.3% (Sevelamer). The percentage of patients that reported at least one treatment-emergent adverse event was 83.2% with PA21 and 76.1% with Sevelamer. A higher proportion of patients withdrew owing to treatment-emergent adverse events with PA21 (15.7%) vs. Sevelamer (6.6%). Mild, transient diarrhea, discolored feces, and hyperphosphatemia were more frequent with PA21; nausea and constipation were more frequent with Sevelamer. After 24 weeks, 99 hemodialysis patients on PA21 were re-randomized into a 3-week superiority analysis of PA21 maintenance dose in 50 patients vs. low dose (250mg per day (ineffective control)) in 49 patients. The PA21 maintenance dose was superior to the low dose in maintaining serum phosphorus control. Thus, PA21 was effective in lowering serum phosphorus in dialysis patients, with similar efficacy to Sevelamer carbonate, a lower pill burden, and better adherence.
