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

Abstract

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.

The effects of non-calcium-based phosphate binders versus calcium-based phosphate binders on cardiovascular calcification and bone remodeling among dialysis patients: a meta-analysis of randomized trials

“…Eighteen trials 4,9,10,[15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] met the predefined inclusion criteria and were included in our meta-analysis ( Figure 1). The 18 trails included 3676 patients (Table 1).…”

“…The 18 trails included 3676 patients (Table 1). CAC score was reported 4,9,10,[15][16][17][18][19][20][21]23,24,[27][28][29] After adjustment for the agreement between reviewers, the j coefficient on the agreement of the included studies was 0.92 (95% confidence interval 0.83 to 0.95), suggesting good agreement between reviewers in data extraction. All studies were randomized controlled trials.…”

“…For iPTH, the heterogeneity was significant difference. We performed sensitivity analyses by excluding the trial 16 of ''follow-up length only 12 weeks''. The heterogeneity was not significant difference, and the results did not change.…”

Stop chronic kidney disease progression: Time is approaching

“…When sevelamer was used in hyperphosphatemic stage 3-4 CKD patients, a significant impact on allcause mortality and the need of dialysis was observed in comparison to calcium carbonate [122] . Sevelamer is not just a calciumfree phosphate binder, but it has additional pleiotropic effects such as correcting certain abnormalities of lipid metabolism [123] , significant decrease in inflammatory parameters including interleukin (IL)-6, sCD14 and hs-CRP [124,125] , reduces serum UA concentration [126] , decrease serum FGF23 [127][128][129] and increases serum level of Klotho [129] . The role of FGF23 and Klotho on the cardiovascular system and progression of CKD will be discussed later in this review.…”

Arterial Calcification in Chronic Kidney Disease: Whom? When? and How to Handle?

“…In addition, sevelamer carries further benefits including entrapment of lipids in the gut lumen, [109] decreased serum inflammatory parameters (including interleukin-6, sCD14, and hs-CRP), [110,111] reduced serum uric acid concentration [112], decreased serum FGF23 [113][114][115], increased serum level of fetuin-A [116] and Klotho [115]. Compared to calcium-based phosphate binders, sevelamer improves endothelial function in CKD patients [117].…”