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


METHODS
Randomized trial with parallel-group design.


METHODS
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.


METHODS
Patients were randomly assigned to 12 months of treatment with sevelamer (n = 91) or calcium carbonate (n = 92).


METHODS
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.


CONCLUSIONS
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.
Division of Nephrology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa, Japan. kakuta@is.icc.u-tokai.ac.jp
Takatoshi
T
Kakuta
Reika
R
Tanaka
Toru
T
Hyodo
Hajime
H
Suzuki
Genta
G
Kanai
Mikako
M
Nagaoka
Hiroo
H
Takahashi
Nobuhito
N
Hirawa
Yoichi
Y
Oogushi
Toshio
T
Miyata
Hiroyuki
H
Kobayashi
Masafumi
M
Fukagawa
Akira
A
Saito
D002114:Calcinosis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D002119:Calcium Carbonate / Q000627:therapeutic use*; D002614:Chelating Agents / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000150:complications / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011073:Polyamines / Q000627:therapeutic use*; D006435:Renal Dialysis; D012189:Retrospective Studies; D000069603:Sevelamer; D016896:Treatment Outcome
D002614:Chelating Agents; D017127:Glycation End Products, Advanced; D011073:Polyamines; D000069603:Sevelamer; D002119:Calcium Carbonate