Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients

Takatoshi Kakuta, Reika Tanaka, Toru Hyodo, Hajime Suzuki, Genta Kanai, Mikako Nagaoka, Hiroo Takahashi, Nobuhito Hirawa, Yoichi Oogushi, Toshio Miyata, Hiroyuki Kobayashi, Masafumi Fukagawa, Akira Saito

Research output: Contribution to journalArticle

96 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)422-431
Number of pages10
JournalAmerican Journal of Kidney Diseases
Volume57
Issue number3
DOIs
Publication statusPublished - 2011 Mar

Keywords

  • Advanced glycation end products
  • coronary artery calcification
  • hemodialysis
  • low-density lipoprotein (LDL) cholesterol
  • pentosidine
  • sevelamer hydrochloride

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients'. Together they form a unique fingerprint.

  • Cite this

    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. (2011). Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients. American Journal of Kidney Diseases, 57(3), 422-431. https://doi.org/10.1053/j.ajkd.2010.10.055