Pleiotropic effects of the non-calcium phosphate binder sevelamer

Nikolov, Igor; Joki, Nobuhiko; Maizel, Julien; Lacour, Bernard; Drüeke, Tilman B.; Massy, Ziad A.

doi:10.1038/sj.ki.5001994

Cited by 36 publications

(39 citation statements)

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“…Prevalent HD patients with hyperphosphatemia (N ϭ 203) were randomly assigned to calcium acetate or sevelamer for 12 mo to achieve target phosphorus levels of 3.5 to 5.5 mg/dl. To control for LDL cholesterol lowering by sevelamer (49,50), atorvastatin was administered to the calcium acetate-treated patients to reduce LDL cholesterol levels to Ͻ70 mg/dl and to sevelamer-treated patients whose LDL cholesterol failed to reach this level. It is interesting that 97% of the calcium-treated patients and 79% of the sevelamer-treated patients received atorvastatin.…”

Section: Effects Of Phosphate Binders On Vcmentioning

confidence: 99%

Ten-Year Experience with Sevelamer and Calcium Salts as Phosphate Binders

Raggi

Vukičević

Moysés

et al. 2010

Clinical Journal of the American Society of Nephrology

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Most patients with chronic kidney disease experience abnormalities in serum calcium, phosphorus, parathyroid hormone, and vitamin D metabolism. These can lead to vascular calcification (VC), which has been associated with increased risk for cardiovascular disease and mortality. Although hyperphosphatemia is believed to be a risk factor for mortality and VC, no randomized trial was ever designed to demonstrate that lowering phosphate reduces mortality. Nonetheless, binders have been used extensively, and the preponderance of evidence shows that sevelamer slows the development of VC whereas calcium salts do not. Four studies have demonstrated a slower progression of VC with sevelamer than with calcium-containing binders, although a fifth study showed nonsuperiority. Conversely, the results on mortality with sevelamer have been variable, and data on calcium-based binders are nonexistent. Improved survival with sevelamer was demonstrated in a small randomized clinical trial, whereas a larger randomized trial failed to show a benefit. In addition, preclinical models of renal failure and preliminary clinical data on hemodialysis patients suggest a potential benefit for bone with sevelamer. Meanwhile, several randomized and observational studies suggested no improvement in bone density and fracture rate, and a few noted an increase in total and cardiovascular mortality in the general population given calcium supplements. Although additional studies are needed, there are at least indications that sevelamer may improve vascular and bone health and, perhaps, mortality in hemodialysis patients, whereas data on calcium-based binders are lacking.

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Section: Effects Of Phosphate Binders On Vcmentioning

confidence: 99%

Ten-Year Experience with Sevelamer and Calcium Salts as Phosphate Binders

Raggi

Vukičević

Moysés

et al. 2010

Clinical Journal of the American Society of Nephrology

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“…In addition to its phosphate-binding effect, sevelamer hydrochloride, a nonabsorbable noncalcium-based hydrogel, has been shown to exert a raft of beneficial pleiotropic actions, including anti-inflammatory effects (15). sevelamer may bind endotoxins and sequester bile acid-LPS complexes in the intestinal tract (16).…”

Section: Introductionmentioning

confidence: 99%

Effect of Phosphate Binders on Serum Inflammatory Profile, Soluble CD14, and Endotoxin Levels in Hemodialysis Patients

Navarro‐González¹,

Mora‐Fernández²,

Fuentes³

et al. 2011

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objectives Hyperphosphatemia and subclinical endotoxemia are important sources of inflammation in HD. Proinflammatory cytokines are strong correlates of soluble CD14 (sCD14) concentrations, an independent predictor of mortality in this population. We evaluated the effects of calcium acetate and sevelamer hydrochloride on serum inflammatory profile, endotoxin concentrations, and sCD14 levels in HD patients.Design, setting, participants, & measurements Prospective, randomized, open-label, parallel design trial. Fiftynine stable HD patients, 30 receiving sevelamer, and 29 receiving calcium acetate were evaluated. Serum levels of inflammatory parameters (high-sensitivity C-reactive protein [hs-CRP], TNF-␣, interleukin (IL)-1, -6, -10, and -18), as well as endotoxin and sCD14 concentrations, were measured at baseline and after 3 months of therapy.Results Serum IL-6 increased in patients receiving calcium acetate, whereas hs-CRP and IL-6 significantly decreased in subjects treated with sevelamer, with IL-10 experiencing a trend to increase (P ϭ 0.052). Serum endotoxin and sCD14 levels did not change after treatment with calcium acetate. However, these parameters decreased by 22.6% and 15.2%, respectively (P Ͻ 0.01), in patients receiving sevelamer. Multiple regression analysis showed that variation in serum endotoxin concentrations was the strongest factor associated with IL-6 change, whereas the only variables independently associated with changes in sCD14 levels were the variations in serum IL-6 and endotoxin concentrations.Conclusions Administration of the noncalcium phosphate binder sevelamer to maintenance HD patients is associated with a significant decrease in hs-CRP, IL-6, serum endotoxin levels and sCD14 concentrations.

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“…decreasing C-reactive protein or increasing the anticalcification mediator fetuin-A). It also seems to improve endothelial dysfunction, oxidative stress, and the clearance of some uremic toxins, and in experimental animals it has been found to prevent uremia-enhanced atherosclerosis progression [63] . On the other hand, sevelamer has adverse effects such as gastrointestinal intolerance (common for the different phosphate binders), the need for a high number of pills and the high price.…”

Section: Phosphate Bindersmentioning

confidence: 99%

Dietary and Pharmacological Control of Calcium and Phosphate Metabolism in Dialysis Patients

Bover¹,

Andrés²,

Lloret³

et al. 2009

Blood Purif

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Chronic kidney disease-mineral and bone disorder is a new term defining a complex syndrome which underlines the need of a systemic approach to disturbances of calcium and phosphate metabolism in patients with renal failure. In recent years, the availability of new phosphorus binders and the appearance of new selective vitamin D receptor activators and calcimimetics have increased our current armamentarium and have changed previous paradigms. All these drugs can be used in combination, acting in distinct yet complementary pathways, with a resultant improvement in their individual clinical profile and reduction in secondary effects, while enhancing the achievement of clinical guideline targets. On the other hand, we should be aware that treatment costs are increasing and most of our knowledge is opinion-based. In this article, we shall consider rational recommendations on the control of calcium, phosphorus and parathyroid hormone while awaiting new evidence. We shall also briefly review some important related issues such as vascular calcification, adynamic bone disease, osteoporosis and the need of parathyroidectomy. Future guidelines may modify current recommendations, but we believe that the lack of an absolute evidence is not equivalent to the lack of awareness of the important problem which chronic kidney disease-mineral and bone disorder represents.

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Pleiotropic effects of the non-calcium phosphate binder sevelamer

Cited by 36 publications

References 50 publications

Ten-Year Experience with Sevelamer and Calcium Salts as Phosphate Binders

Ten-Year Experience with Sevelamer and Calcium Salts as Phosphate Binders

Effect of Phosphate Binders on Serum Inflammatory Profile, Soluble CD14, and Endotoxin Levels in Hemodialysis Patients

Dietary and Pharmacological Control of Calcium and Phosphate Metabolism in Dialysis Patients

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