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-65259

Cited by 43 publications

(31 citation statements)

References 21 publications

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“…In a recent study, 36 hemodialysis patients were treated with colesevelam 1.5 g before meals for 6 months. Investigators noted a 20% reduction in non-HDL-C (p Ͻ 0.0001) and a 63% reduction in median C-reactive protein values (p ϭ 0.0259) (49).…”

Section: Safety Of Other Lipid-lowering Drugsmentioning

confidence: 98%

Managing Dyslipidemia in Chronic Kidney Disease

Harper

Jacobson

2008

Journal of the American College of Cardiology

169

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The incidence of chronic kidney disease (CKD) in the U.S. continues to increase, and now over 10% of the U.S. population has some form of CKD. Although some patients with CKD will ultimately develop renal failure, most patients with CKD will die of cardiovascular disease before dialysis becomes necessary. Patients with CKD have major proatherogenic lipid abnormalities that are treatable with readily available therapies. The severe derangements seen in lipoprotein metabolism in patients with CKD typically results in high triglycerides and low high-density lipoprotein (HDL) cholesterol. Because of the prevalence of triglyceride disorders in patients with CKD, after treating patients to a low-density lipoprotein goal, non-HDL should be calculated and used as the secondary goal of treatment. A review of the evidence from subgroup analysis of several landmark lipid-lowering trials supports treating dyslipidemia in mild to moderate CKD patients with HMG-CoA reductase inhibitors. The evidence to support treating dyslipidemia in hemodialysis patients, however, has been mixed, with several outcome trials pending. Patients with CKD frequently have mixed dyslipidemia and often require treatment with multiple lipid-lowering drugs. Although statins are the cornerstone of therapy for most patients with CKD, differences in their pharmacokinetic properties give some statins a safety advantage in patients with advanced CKD. Although most other lipid-lowering agents can be used safely with statins in combination therapy in patients with CKD, the fibrates are renally metabolized and require both adjustments in dose and very careful monitoring due to the increased risk of rhabdomyolysis. After reviewing the safety and dose alterations required in managing dyslipidemia in patients with CKD, a practical treatment algorithm is proposed.

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Section: Safety Of Other Lipid-lowering Drugsmentioning

confidence: 98%

Managing Dyslipidemia in Chronic Kidney Disease

Harper

Jacobson

2008

Journal of the American College of Cardiology

169

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“…Plusieurs autres essais cliniques ont é galement rapporté un effet bé né fique du sé vé lamer sur les profils lipidiques des patients dialysé s [13,30,31], y compris chez l'enfant [16]. Pour finir, le traitement par sé vé lamer d'un groupe de patients hé modialysé s a ré sulté en une diminution de l'é paisseur intima-mé dia carotidienne (un facteur de risque d'é vé nement CV dans la population gé né rale comme chez le patient insuffisant ré nal chronique).…”

Section: Effet Du Sé Vé Lamer Sur Le Profil Lipidique Dans La Mrcunclassified

“…Il est dé montré que l'administration de sé vé lamer induit une diminution des marqueurs de l'inflammation, ce que ne font pas les ché lateurs à base de calcium [29,31]. Dans une é tude prospective randomisé e effectué e chez 108 patients hé modialysé s chroniques, le traitement par sé vé lamer, mais pas par l'acé tate de calcium, a conduit à des baisses importantes des taux de hs-CRP sé rique (À4,8 AE 25,8 mg/L pour une valeur initiale de 15,3 AE 19,3 mg/L, moyennes AE é carts types ; p = 0,012) et de bêta-2-microglobuline sé rique (À0,09 AE 0,31 mg/dL pour une valeur initiale de 3,08 AE 0,50 mg/dL ; p = 0,018) [29].…”

Section: Effet Du Sé Vé Lamer Sur L'inflammationunclassified

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Effets pléïotropes du sévélamer, précurseur d’agent chélateur de la voie intestinale

Massy

Maizel

2014

Néphrologie & Thérapeutique

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“…The use of sevelamer has been associated with a marked reduction in C-reactive protein levels in patients with kidney failure receiving hemodialysis [13, 14], along with the halting of progressive coronary artery calcification [13]. This might be ascribed in part to the lowering of phosphate, LDL cholesterol or C-reactive protein levels [14]. …”

Section: Introductionmentioning

confidence: 99%

Endotoxin-Binding Affinity of Sevelamer Hydrochloride

Perianayagam

Jaber²

2008

Am J Nephrol

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Background: Sevelamer hydrochloride has been shown to attenuate circulating biomarkers of inflammation in patients with chronic kidney failure. We hypothesize that sevelamer hydrochloride binds bacterial endotoxin (ET) resulting in a decrease in ET levels and cytokine production. Methods: To assess the ET-binding affinity of sevelamer hydrochloride, purified Escherichia coli ET was incubated with sevelamer hydrochloride (0–50 mg/ml). After incubation, ET was measured in supernatants. In addition, THP-1-derived monocytes were co-incubated with supernatants of sevelamer hydrochloride and ET. After 24-hour incubation, TNF-α was measured. The effect of pH on the ET-binding affinity of sevelamer hydrochloride, as well as cooperative binding between ET and phosphate for sevelamer hydrochloride were assessed. Results: Sevelamer hydrochloride exhibited time- and dose-dependent binding affinity for ET, resulting in a marked reduction in free ET levels. The 1-hour dose-dependent ET-binding effect of sevelamer hydrochloride translated into a marked reduction in TNF-α levels. Varying the pH conditions did not affect the ET-binding affinity of sevelamer hydrochloride. The addition of phosphate (0–50 mM) resulted in a further reduction in free ET levels, translating into a further increase in the binding affinity of sevelamer hydrochloride for ET. Conclusions: This study demonstrates that sevelamer hydrochloride binds to ET, thereby reducing free ET and cytokine levels. Positive cooperative binding was also noted between phosphate and ET for sevelamer hydrochloride. This study supports the hypothesis that sevelamer hydrochloride might bind to ET in the intestinal lumen and reduce systemic inflammation. Animal and human studies are required to examine this hypothesis.

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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 43 publications

References 21 publications

Managing Dyslipidemia in Chronic Kidney Disease

Managing Dyslipidemia in Chronic Kidney Disease

Effets pléïotropes du sévélamer, précurseur d’agent chélateur de la voie intestinale

Endotoxin-Binding Affinity of Sevelamer Hydrochloride

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