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Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients.
Am J Kidney Dis. 2011 Mar; 57(3):422-31.AJ

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.

Authors+Show Affiliations

Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan. kakuta@is.icc.u-tokai.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21239096

Citation

Kakuta, Takatoshi, et al. "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 : the Official Journal of the National Kidney Foundation, vol. 57, no. 3, 2011, pp. 422-31.
Kakuta T, Tanaka R, Hyodo T, et al. Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients. Am J Kidney Dis. 2011;57(3):422-31.
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 : the Official Journal of the National Kidney Foundation, 57(3), 422-31. https://doi.org/10.1053/j.ajkd.2010.10.055
Kakuta T, et al. Effect of Sevelamer and Calcium-based Phosphate Binders On Coronary Artery Calcification and Accumulation of Circulating Advanced Glycation End Products in Hemodialysis Patients. Am J Kidney Dis. 2011;57(3):422-31. PubMed PMID: 21239096.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of sevelamer and calcium-based phosphate binders on coronary artery calcification and accumulation of circulating advanced glycation end products in hemodialysis patients. AU - Kakuta,Takatoshi, AU - Tanaka,Reika, AU - Hyodo,Toru, AU - Suzuki,Hajime, AU - Kanai,Genta, AU - Nagaoka,Mikako, AU - Takahashi,Hiroo, AU - Hirawa,Nobuhito, AU - Oogushi,Yoichi, AU - Miyata,Toshio, AU - Kobayashi,Hiroyuki, AU - Fukagawa,Masafumi, AU - Saito,Akira, Y1 - 2011/01/15/ PY - 2009/10/13/received PY - 2010/10/26/accepted PY - 2011/1/18/entrez PY - 2011/1/18/pubmed PY - 2011/9/29/medline SP - 422 EP - 31 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 57 IS - 3 N2 - 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. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/21239096/Effect_of_sevelamer_and_calcium_based_phosphate_binders_on_coronary_artery_calcification_and_accumulation_of_circulating_advanced_glycation_end_products_in_hemodialysis_patients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(10)01669-0 DB - PRIME DP - Unbound Medicine ER -