Effect of Sevelamer on Dyslipidemia and Chronic Inflammation in Maintenance Hemodialysis Patients

Yamada, Kazuhiro; Fujimoto, Shouichi; Tokura, Takeshi; Fukudome, Keiichi; Ochiai, Hideyuki; Komatsu, Hiroyuki; Sato, Yuji; Hara, Seiichiro; Eto, Tanenao

doi:10.1081/jdi-200065259

Cited by 32 publications

(17 citation statements)

References 21 publications

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“…Ferramosca et al (22) showed that sevelamer treatment resulted in significant reductions of serum phosphorus and CRP levels. Likewise, Yamada et al (23) observed a significant decrease of CRP during sevelamer therapy, which was correlated with the change of phosphorus. More recently, a subanalysis from the Nutritional and Inflammatory Evaluation of Dialysis Patients Study showed that patients receiving sevelamer were more likely to have a lower CRP concentration when compared with patients treated with calcium-based phosphate binders (24).…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…The kinetics of the HDL changes could not be characterized because lipid panels were drawn only at the start and completion of the treatment arms. Of note, most patients in our study were concomitantly treated with sevelamer, which lowers LDL via bile acid binding (27,28). This may obscure further lipid lowering by niacinamide.…”

Section: Discussionmentioning

confidence: 99%

A Randomized, Double-Blind, Placebo-Controlled Trial of Niacinamide for Reduction of Phosphorus in Hemodialysis Patients

Cheng

Young

Huang

et al. 2008

Clinical Journal of the American Society of Nephrology

105

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Background and objectives: Niacinamide inhibits intestinal sodium/phosphorus transporters and reduces serum phosphorus in open-label studies. A prospective, randomized, double-blind, placebo-controlled crossover trial was performed for assessment of the safety and efficacy of niacinamide.Design, setting, participants, & measurements: Hemodialysis patients with phosphorus levels >5.0 mg/dl were randomly assigned to 8 wk of niacinamide or placebo, titrated from 500 to 1500 mg/d. After a 2-wk washout period, patients switched to 8 wk of the alternative therapy. Vitamin D analogs and calcimimetics were held constant; phosphorus binders were not changed unless safety criteria were met.Results: Thirty-three patients successfully completed the trial. Serum phosphorus fell significantly from 6.26 to 5.47 mg/dl with niacinamide but not with placebo (5.85 to 5.98 mg/dl). A concurrent fall in calcium-phosphorus product was seen with niacinamide, whereas serum calcium, intact parathyroid hormone, uric acid, platelet, triglyceride, LDL, and total cholesterol levels remained stable in both arms. Serum HDL levels rose with niacinamide (50 to 61 mg/dl but not with placebo. Adverse effects were similar between both groups. Among patients who were >80% compliant, results were similar, although the decrease in serum phosphorus with niacinamide was more pronounced (6.45 to 5.28 mg/dl) and the increase in HDL approached significance (49 to 58 mg/dl).Conclusions: In hemodialysis patients, niacinamide effectively reduces serum phosphorus when co-administered with binders and results in a potentially advantageous increase in HDL cholesterol. Further study in larger randomized trials and other chronic kidney disease populations is indicated.

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“…5 The direct association of hyperphosphatemia with CRP, as derived from our data, might also serve to duplicate the known cardiovascular disease paradigm linking blood cholesterol levels, dietary intake, and cardiovascular risk with respect to blood phosphate. 9,10 In conclusion, the reduction of serum PO 4 , induced by the chitosan chewing gum, in sevelamer-resistant hemodialysis patients and its relationship with hsCRP reduction, shown in the present study, joined with the demonstration "in vitro" that increased PO 4 concentration impairs endothelial integrity via induction of oxidative stress, 4 and with the evidence that sevelamer reduces both hsCRP and serum phosphate, 5 provide further evidence to support a direct proinflammatory role of hyperphosphatemia. All together these results strengthen the role of serum phosphate as "non-traditional" risk factor for cardiovascular disease, which has been shown even in the normal population.…”

Section: Discussionmentioning

confidence: 99%

Reduction of Hyperphosphatemia is Related with the Reduction of C-Reactive Protein in Dialysis Patients. Study in Sevelamer-Resistant Dialysis Patients Treated with Chitosan Chewing Gum as Salivary Phosphate Binder

et al. 2011

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Background: In end-stage renal disease (ESRD) hyperphosphatemia associates with vascular calcifications and cardiovascular events derived from endothelial dysfunction. In dialysis patients, C-reactive protein (CRP), a marker of inflammation, associates with cardiovascular mortality. Increased PO 4 concentration impairs endothelial integrity via induction of oxidative stress, and sevelamer, a phosphate binder, showed anti-inflammatory effect reducing CRP, which paralleled PO 4 reduction. To give support to a direct proinflammatory role of hyperphosphatemia "per se," we have considered previously studied dialysis patients with sevelamer-"resistant" hyperphosphatemia, who were treated with a chitosan-loaded chewing gum, as salivary phosphate binder, in addition to sevelamer, reduced serum PO 4 to normal, to retrospectively evaluate their CRP and the relationship with hyperphosphatemia and calcium × phosphate (Ca × PO 4 ) product. Patients and Methods: High sensitive (hs) CRP of 13 previously studied hemodialysis patients with sevelamer-resistant hyperphosphatemia was evaluated with immunonephelometry. Results: Chitosan chewing gum use reduced hsCRP (from 1.38 ± 0.61 to 0.39 ± 0.16 mg/L after the gum, p < 0.0002), which returned to baseline after 4 weeks from gum discontinuation (1.25 ± 0.41). hsCRP reduction paralleled serum PO 4 reduction: from 7.60 ± 0.91 mg/dL to 5.18 ± 0.73 (after the gum) (p < 0.00001), returning to baseline (7.55 ± 0.75) after gum discontinuation. hsCRP reduction directly correlated with PO 4 reduction (p = 0.029). Conclusion: The relationship in sevelamer-resistant dialysis patients between the reduction of serum PO 4 , induced by the chitosan-loaded chewing gum, and CRP reduction supports also in humans a proinflammatory role of hyperphosphatemia "per se" derived from "in vitro" studies. This further contributes to the high cardiovascular risk of ESRD patients making their serum phosphate in the normal range of vital importance.

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Effect of Sevelamer on Dyslipidemia and Chronic Inflammation in Maintenance Hemodialysis Patients

Abstract: Hs-CRP levels were reduced by sevelamer administration, as well as non-HDL-C, P, and the Ca x P product. Sevelamer may have an anti-inflammatory effect, in addition to lowering phosphate and lipid levels in HD patients.

Cited by 32 publications

References 21 publications

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

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

A Randomized, Double-Blind, Placebo-Controlled Trial of Niacinamide for Reduction of Phosphorus in Hemodialysis Patients

Reduction of Hyperphosphatemia is Related with the Reduction of C-Reactive Protein in Dialysis Patients. Study in Sevelamer-Resistant Dialysis Patients Treated with Chitosan Chewing Gum as Salivary Phosphate Binder

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