Endotoxin Binding by Sevelamer: Potential Impact on Nutritional Status

Table 1

Recent interventional trials of sevelamer and impact on proinflammatory biomarkers.

Authors	Study design	Treatment groups	Outcomes/results	𝑃 value
Hauser et al., 2010 [25]	Nonclinical animal model; (Rats surgical nephrectomy-induced uremia)	Rats fed normal chow (𝑛=7); or; 3% sevelamer carbonate added to chow for 60 days (𝑛=5); (Plasma levels of TNF-𝛼, ET, and CRP; measured at 7, 30, and 60 days)	Plasma levels were reduced in sevelamer-treated rats versus control uremic rats: TNF-𝛼; ET; There was no significant change in CRP levels	<0.05; <0.005
Sun et al., 2009 [19]	Cross-sectional study of 46; stable HD patients	Sevelamer HCl (𝑛=30); or; nonsevelamer (𝑛=16); (CRP, IL-6, and ET levels (at two consecutive blood samples during dialysis))	Plasma levels in patients on sevelamer versus not on sevelamer: ET: 0.23 ± 0.01 versus 0.3 ± 0.01 EU/mL; IL-6: 9.6 ± 1.2 versus 10.1 ± 1.7 pg/mL; CRP: 16.1 ± 1.2 versus 15.6 ± 2.2 mcg/mL	0.001; 0.927; 0.892
Stinghen et al., 2010 [20]	Prospective study in stable 26 HD patients eligible for switch to sevelamer (per KDOQI guidelines)	All (𝑛=26) patients started on sevelamer HCl; plasma  hsCRP and ET measured; at Baseline; and; at 6 months	Plasma concentrations of hsCRP and ET decreased from baseline, mean (SD):^‡; hsCRP: 4.8 ± 1.2 to 0.44 ± 0.12 mg/L; ET: 3.6 ± 0.8 to 1.2 ± 0.6 EU/mL	<0.001; <0.005
Navarro-González et al., 2011 [49]	Prospective, randomized, open-label, and parallel design trial in stable HD patients; (𝑁=59)	Sevelamer HCl (𝑛=30); or; calcium acetate (𝑛=29); (CRP, TNF-𝛼, IL-1, IL-6, IL-10, IL-18, sCD14, and ET serum levels measured at baseline and 3 months after therapy)	Serum levels in the sevelamer group at baseline versus at 3 month followup; median (interquartile range):^†; ET: 0.58 (0.51–0.60) down to 0.42 (0.27–0.54) EU/mL; CRP: 6.9 (5.9–8) down to 5.9 (5.1–10) mg/mL; IL-6: 5 (3–9.1) down to 4.9 (2.68–8.6) pg/mL	0.001; 0.001; 0.01
Vlassara et al., 2012 [50]	Single-center, randomized, 2-month, open-label, intention-to-treat, and crossover study in patients with DM-2 stage 2–4 CKD; (𝑁=20)	Sevelamer carbonate; versus; calcium carbonate; HbA1c, FGF-23, TNF-𝛼, and hsCRP measured after 8 weeks on each treatment modality (separated by 1 week wash-out period)	Estimated effect of sevelamer relative to calcium carbonate (after adjusting for period of treatment):^¶; HbA1c: −0.67 (95% CI, from −1.25 to −0.10); FGF-23: −59.74 (95% CI, from −116.35 to −3.1); TNF-𝛼: −7.2 (95% CI, from −11.01 to −3.38)	0.02; 0.04; <0.001

HD: hemodialysis; TNF-𝛼: tumor necrosis factor; IL: interleukin; sCD: soluble cluster differentiation; ET: endotoxin; hsCRP: high sensitivity C-reactive protein; FGF-23: fibroblast growth factor-23; HbA1c: hemoglobin A1c; CKD: chronic kidney disease, KDOQI: national kidney foundation disease outcomes quality initiative; DM-2: diabetes mellitus type-2.
^†sCD14 also showed significant change from baseline in the sevelamer groups. No significant change in the calcium acetate group or in the other outcomes.
^‡No control group.
^¶Effect on hsCRP levels did not differ significantly between the groups.