Effect of phosphate binders on serum inflammatory profile, soluble CD14, and endotoxin levels in hemodialysis patients

Abstract

Background 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. Fifty-nine 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-α, 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 = 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 < 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.

Figure 1.

Flow chart of patients included in the study.

Figure 2.

Mean percent variation respect to baseline in serum concentration of inflammatory parameters in the calcium acetate and sevelamer groups at the end of the study. hsCRP, high-sensitivity C-reactive protein.

Figure 3.

Mean percent variation respect to baseline in serum endotoxin concentration and soluble CD14 levels in the calcium acetate and sevelamer groups at the end of the study.

Figure 4.

Comparison of the mean percent variation of the ratios of proinflammatory (TNF-α, IL-1, IL-6 and IL-18) to the anti-inflammatory cytokine (IL-10) between the calcium acetate and sevelamer groups at the end of the study.