TY - JOUR
T1 - Pleiotropic effects of sevelamer beyond phosphate binding in end-stage renal disease patients
T2 - A randomized, open-label, parallel-group study
AU - Lin, Yu Feng
AU - Chien, Chiang Ting
AU - Kan, Wei Chih
AU - Chen, Yung Ming
AU - Chu, Tzong Shinn
AU - Hung, Kuan Yu
AU - Tsai, Tun Jun
AU - Wu, Kwan Dun
AU - Wu, Ming Shiou
N1 - Funding Information:
This study was supported financially by the Improving Dialysis Quality Research Funds, Ta-Tung Kidney Foundation. The funding agency played no role in study design, data collection, data analysis, data interpretation or writing of the report, or in the decision to submit the report for publication. The corresponding author had full access to all data in the study and had the final responsibility for the decision to submit for publication. The authors have no conflicts of interest that are directly relevant to the content of this study.
PY - 2011
Y1 - 2011
N2 - Background and Objective: Hyperphosphataemia in end-stage renal disease (ESRD) is a major contributor to the development of cardiovascular disease. It has been proposed that the phosphate binder sevelamer has pleiotropic properties. The aim of this study was to evaluate the effects of sevelamer compared with calcium acetate on serum lipid profiles, uric acid and reactive oxygen species in haemodialysis patients with hyperphosphataemia. Methods: An 8-week, randomized, open-label, parallel-group study was conducted after a 2-week washout period. A total of 52 patients with ESRD on maintenance haemodialysis were screened for enrolment; 26 patients were randomized to each of the sevelamer and calcium acetate groups. Reactive oxygen species (ROS) production, i.e. superoxide and hydrogen peroxide (H2O 2)-related radicals, were detected by chemiluminescence measurement with lucigenin and luminol, respectively. Results: There were no significant differences between treatment groups in changes in serum phosphorus (p = 0.378) and adjusted serum calcium levels (p = 0.980), but there were more hypercalcaemic events in the calcium acetate group (12.0% vs 3.7%) during treatment. Total serum cholesterol (p < 0.001) and low-density lipoprotein (LDL) cholesterol (p < 0.001) levels decreased significantly compared with baseline in the sevelamer group. The decreases in total serum cholesterol and LDL cholesterol were correlated with the reductions in serum phosphorus levels during sevelamer treatment (correlation coefficient [r] = 0.266 and 0.386, respectively). Serum uric acid decreased significantly in the sevelamer group (p = 0.020), and this change was correlated with serum phosphorus changes (r = 0.458). Decreases in plasma H2O2-related radicals, the major oxidative stressor in ROS (p < 0.001), but not superoxide (p = 0.593), were observed after sevelamer treatment. Conclusion: The improvements in multiple lipid surrogates, uric acid and ROS seen in this study show that sevelamer is a promising therapy for treatment of hyperphosphataemia in maintenance haemodialysis patients with a high risk of cardiovascular disease.
AB - Background and Objective: Hyperphosphataemia in end-stage renal disease (ESRD) is a major contributor to the development of cardiovascular disease. It has been proposed that the phosphate binder sevelamer has pleiotropic properties. The aim of this study was to evaluate the effects of sevelamer compared with calcium acetate on serum lipid profiles, uric acid and reactive oxygen species in haemodialysis patients with hyperphosphataemia. Methods: An 8-week, randomized, open-label, parallel-group study was conducted after a 2-week washout period. A total of 52 patients with ESRD on maintenance haemodialysis were screened for enrolment; 26 patients were randomized to each of the sevelamer and calcium acetate groups. Reactive oxygen species (ROS) production, i.e. superoxide and hydrogen peroxide (H2O 2)-related radicals, were detected by chemiluminescence measurement with lucigenin and luminol, respectively. Results: There were no significant differences between treatment groups in changes in serum phosphorus (p = 0.378) and adjusted serum calcium levels (p = 0.980), but there were more hypercalcaemic events in the calcium acetate group (12.0% vs 3.7%) during treatment. Total serum cholesterol (p < 0.001) and low-density lipoprotein (LDL) cholesterol (p < 0.001) levels decreased significantly compared with baseline in the sevelamer group. The decreases in total serum cholesterol and LDL cholesterol were correlated with the reductions in serum phosphorus levels during sevelamer treatment (correlation coefficient [r] = 0.266 and 0.386, respectively). Serum uric acid decreased significantly in the sevelamer group (p = 0.020), and this change was correlated with serum phosphorus changes (r = 0.458). Decreases in plasma H2O2-related radicals, the major oxidative stressor in ROS (p < 0.001), but not superoxide (p = 0.593), were observed after sevelamer treatment. Conclusion: The improvements in multiple lipid surrogates, uric acid and ROS seen in this study show that sevelamer is a promising therapy for treatment of hyperphosphataemia in maintenance haemodialysis patients with a high risk of cardiovascular disease.
KW - Calcium-acetate, therapeutic use
KW - Haemodialysis
KW - Renal-failure
KW - Sevelamer, therapeutic use
UR - https://www.scopus.com/pages/publications/79952389123
UR - https://www.scopus.com/pages/publications/79952389123#tab=citedBy
U2 - 10.2165/11539120-000000000-00000
DO - 10.2165/11539120-000000000-00000
M3 - Article
C2 - 21299254
AN - SCOPUS:79952389123
SN - 1173-2563
VL - 31
SP - 257
EP - 267
JO - Clinical Drug Investigation
JF - Clinical Drug Investigation
IS - 4
ER -
SDG 3 健康與福祉