Sevelamer Hydrochloride Binds Phosphate Released from Phytate in Chicks Fed 1α-Hydroxy Cholecalciferol

Bobeck, Elizabeth; Meyer, Katie M.; Helvig, Christian; Petkovich, Martin; Cook, Mark E.

doi:10.1053/j.jrn.2011.12.005

Cited by 6 publications

(5 citation statements)

References 27 publications

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“…The compounds (such as sevelamer carbonate, lanthanum, and iron salts) directly bind luminal phosphate, making it unavailable for absorption (117). The binders effectively reduce dietary phosphate absorption in patients on dialysis (118) and reduce urinary phosphate excretion by 20%-50% in patients with CKD stage 3 or 4 who are normophosphatemic (119).…”

Section: Bindersmentioning

confidence: 99%

Phosphate Toxicity in CKD: The Killer among Us

Ritter¹,

Slatopolsky²

2016

CJASN

119

113

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Maintenance of a normal serum phosphate level depends on absorption in the gut, reabsorption and excretion by the kidney, and the flux between the extracellular and skeletal pools. Phosphate homeostasis is a coordinated, complex system of crosstalk between the bone, intestine, kidney, and parathyroid gland. Dysfunction of this system has serious clinical consequences in healthy individuals and those with conditions, such as CKD, in which hyperphosphatemia is associated with increased risks of cardiovascular morbidity and mortality. The last halfcentury of renal research has helped define the contribution of the parathyroid hormone, calcitriol, fibroblast growth factor 23, and Klotho in the regulation of phosphate. However, despite new discoveries and insights gained during this time, what remains unchanged is the recognition that phosphate retention is the initiating factor for the development of many of the complications observed in CKD, namely secondary hyperparathyroidism and bone and cardiovascular diseases. Controlling phosphate load remains the primary goal in the treatment of CKD. This review discusses the clinical effects of dysregulated phosphate metabolism, particularly in CKD, and its association with cardiovascular disease. The importance of early control of phosphate load in the treatment of CKD is emphasized, and the latest research in the treatment of phosphate retention is discussed.

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Section: Bindersmentioning

confidence: 99%

Phosphate Toxicity in CKD: The Killer among Us

Ritter¹,

Slatopolsky²

2016

CJASN

119

113

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“…Sevelamer HCl has been shown to be effective at treating adenine-induced hyperphosphatemia in rats [8,10], and 5/6 nephrectomy-induced hyperphosphatemia in mice [34] and rats [35]. We have recently demonstrated in chicks that sevelamer HCl was effective in preventing the absorption of phosphate liberated from the diet due to the treatment of calcitriol [17]. In this report, we found that while sevelamer HCl caused a modest reduction in serum FGF23 after 14 days of supplementation in adenine treated mice, sevelamer HCl was ineffective at preventing hyperphosphatemia in this model.…”

Section: Discussionmentioning

confidence: 99%

“…Mice were fed the diet as described in experiment 1 with or without a phosphate binder (1% sevelamer HCl, Genzyme Corporation, Cambridge, MA; replacing a cellulose filler in the diet) and with or without daily adenine gavage (0 or 4 mg/day in 200 μl ddH 2 O, as described above) to provide the following treatment groups; 1) Control diet with 0 mg adenine gavage; 2) 1% dietary sevelamer HCl with 0 mg adenine gavage; 3) Control diet with 4 mg adenine gavage; or 4) 1% dietary sevelamer HCl with 4 mg adenine gavage. Concentration of sevelamer was based on previous experiments in chick diets where 1% was successful in reducing plasma phosphate and bone ash [17], as well as the calculation that 1 g sevelamer can bind 0.45 g phosphate, hence 1% sevelamer could bind up to 80% of the phosphate in the mouse diet (which contains 0.56% phosphate [18]). The remaining 0.13% phosphate in the diet would leave the mice severely deficient.…”

Section: Methodsmentioning

confidence: 99%

Adenine-induced hyperphosphatemia in a murine model of renal insufficiency

Bobeck¹,

Piccione²,

Bishop³

et al. 2017

Nephrol Renal Dis

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Hyperphosphatemia in chronic kidney disease (CKD) patients is a risk factor for cardiovascular events, progressive kidney failure, and mortality. Improved therapeutic interventions to control hyperphosphatemia depend greatly on robust animal models that recapitulate the CKD disease process. Murine-based models of CKD as compared to rat models present significant advantages due to available genetic knockout lines that permit mechanistic dissection of CKD etiologies. The rat adenine model of renal failure has been extensively studied, and studies are now emerging describing adenine-induced renal failure in murine models. However, these newly developed murine models have not fully described the responses to calcitriol and phosphate binders, and the reported effects of adenine on serum phosphate is often lacking in murine models. Therefore, the objectives of this study were: 1) To induce hyperphosphatemia in mice using adenine with minimal mortality, and 2) Report the influence of calcitriol and phosphate binders on the disease process through measurement of serum phosphate and histology. In one approach, C57BL/6 male mice gavaged with 4 or 6 mg adenine/day, as compared to 0 mg adenine/day developed hyperphosphatemia, with low mortality. In a second approach, calcitriol exacerbated adenine-induced increases in serum phosphate at day 7 of adenine administration (p<0.05). Notably, adenine treated mice had 4-fold increased stomach weights vs. non-adenine treated mice (p<0.0001). The addition of a phosphate binder (experiment 3, sevelamer hydrochloride) was ineffective at preventing an adenine-induced increase in blood phosphate, a finding that likely resulted from adenine's inhibition of gastric emptying. We report the successful use of adenine to induce hyperphosphatemia, that the hyperphosphatemic status is exacerbated by calcitriol, and a limitation of the model for studying oral therapies for hyperphosphatemia.

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“…However, the use of active vitamin D sterols increases the bioavailability of phytate phosphate, 21 – 25 which can lead to an increase of serum phosphorus. Fortunately, sevelamer was effective at binding phytate phosphorus that is liberated by active vitamin D. 26 Hence, sevelamer was more effective in People’s Republic of China. Another reason is probably that the body size of Chinese are generally smaller, so the drug dosage is relatively enough.…”

Section: Monotherapymentioning

confidence: 99%

Practical use of sevelamer in chronic kidney disease patients on dialysis in People’s Republic of China

Meng¹,

Fu²

2015

TCRM

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Hyperphosphatemia is a common complication of dialysis patients. Only 38.5% of Chinese dialysis patients met the Kidney Disease Outcomes Quality Initiative defined targets for serum phosphate. Sevelamer is a high molecular weight cationic hydrogel polymer that prevents absorption of dietary phosphate by binding it in the gastrointestinal tract. In Chinese trials, it was confirmed that sevelamer had better efficacy than calcium carbonate in terms of reducing the serum level of phosphorus and calcium-phosphate product. Sevelamer can also reduce the levels of lipid parameters and improve the micro-inflammatory state. When sevelamer was combined with other treatments, it elicited superior effects on calcium phosphorus metabolism, secondary hyperparathyroidism, and renal osteodystrophy. Combination treatment of sevelamer and traditional Chinese medicine has the unique advantage. However, sevelamer is associated with a high incidence of gastrointestinal adverse effects in Chinese patients. Although more effective, the practical use of sevelamer is not very common because it is expensive and not paid by medical insurance. This article provides a comprehensive review of the practical use of sevelamer in chronic kidney disease patients on dialysis in People’s Republic of China.

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Sevelamer Hydrochloride Binds Phosphate Released from Phytate in Chicks Fed 1α-Hydroxy Cholecalciferol

Cited by 6 publications

References 27 publications

Phosphate Toxicity in CKD: The Killer among Us

Phosphate Toxicity in CKD: The Killer among Us

Adenine-induced hyperphosphatemia in a murine model of renal insufficiency

Practical use of sevelamer in chronic kidney disease patients on dialysis in People’s Republic of China

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Sevelamer Hydrochloride Binds Phosphate Released from Phytate in Chicks Fed 1α-Hydroxy Cholecalciferol

Cited by 6 publications

References 27 publications

Phosphate Toxicity in CKD: The Killer among Us

Phosphate Toxicity in CKD: The Killer among Us

Adenine-induced hyperphosphatemia in a murine model of renal insufficiency

Practical use of sevelamer in chronic kidney disease patients on dialysis in People&rsquo;s Republic of China

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Product

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Practical use of sevelamer in chronic kidney disease patients on dialysis in People’s Republic of China