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Title: Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients.
Author: Kakuta T, Tanaka R, Hyodo T, Suzuki H, Kanai G, Nagaoka M, Takahashi H, Hirawa N, Oogushi Y, Miyata T, Kobayashi H, Fukagawa M, Saito A.
Journal: Am J Kidney Dis; 2011 Mar; 57(3):422-31. PubMed ID: 21239096.
Abstract:
BACKGROUND: Some trials have indicated that coronary artery calcification progresses more slowly in sevelamer-treated dialysis patients than in those using calcium-based binders. Effects of phosphate binders on circulating advanced glycation end products (AGEs) are unknown. STUDY DESIGN: Randomized trial with parallel-group design. SETTING & PARTICIPANTS: 183 adult (aged >20 years) patients on maintenance hemodialysis therapy at 12 dialysis facilities with a mean vintage of 118 ± 89 (median, 108) months. Dialysate calcium concentration was 2.5 mEq/L, and dietary calcium was not controlled. INTERVENTION: Patients were randomly assigned to 12 months of treatment with sevelamer (n = 91) or calcium carbonate (n = 92). OUTCOMES & MEASUREMENTS: Primary outcome measures were change from baseline in coronary artery calcification score (CACS) determined at study entry and completion using multislice computed tomography and the proportion of patients with a ≥ 15% increase in CACS. Blood parameters were determined at study entry and 2-week intervals, and levels of plasma pentosidine, a representative AGE, were determined at study entry, 6 months, and study completion. RESULTS: 79 (86.8%) and 84 (91.3%) patients in the sevelamer and calcium-carbonate arms completed the treatment, respectively. Both binders were associated with an increase in mean CACS: 81.8 (95% CI, 42.9-120.6) and 194.0 (139.7-248.4), respectively (P < 0.001 for both). After adjustment for baseline values, the increase in the sevelamer group was 112.3 (45.8-178) less (P < 0.001). Percentages of patients with a ≥ 15% increase in CACS were 35% of the sevelamer group and 59% of the calcium-carbonate group (P = 0.002). Plasma pentosidine levels increased with calcium carbonate but not [corrected] sevelamer treatment (P < 0.001). Sevelamer use was associated with decreased risk of a ≥ 15% increase in CACS regardless of baseline blood parameters, pentosidine level, and CACS. LIMITATIONS: Treatment duration was relatively short, some sevelamer-treated patients (7 of 79) received calcium carbonate, and washout could not be performed. CONCLUSIONS: The data suggest that sevelamer treatment slowed the increase in CACS and suppressed AGE accumulation.

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