Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis - A randomized clinical trial
Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis - A randomized clinical trial
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DOI：
10.1002/art.20781
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发表时间：
2005-01-01
影响因子：
--
通讯作者：
Chertow, GM
中科院分区：
文献类型：
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作者：
Garg, JP;Chasan-Taber, S;Chertow, GM
目标。痛风影响了很大一部分晚期慢性肾脏疾病患者，而高尿酸血症可能会增加心血管疾病的风险。终末期肾病患者禁用几种低尿酸血症药物。Sevelamer是一种未被吸收的水凝胶，可以结合肠道中的磷和胆汁酸。短期和开放式研究的结果表明，西维拉姆可能会降低尿酸的浓度，尿酸是另一种有机阴离子。我们进行了这项研究，以验证我们的假设，即西维拉姆引起的血尿酸浓度的降低将在一项长期、随机、临床试验中得到证实，该试验比较了西维拉姆和钙基磷酸盐粘结剂。在一项国际多中心临床试验中，200名接受维持性血液透析的受试者被随机分配接受七胺磷或钙基磷结合剂。169名受试者(85%)获得了基线和研究结束时尿酸浓度的数据；从基线到研究结束时尿酸浓度的变化是有趣的结果。基线临床特征，包括平均尿酸浓度，在随机分配接受西维拉姆和钙基磷酸盐结合剂的受试者中相似。服用西维拉姆的受试者尿酸浓度的平均变化(从基线到研究结束)明显更大(-0.64 mg/dl对-0.26 mg/dl；P=0.03)。当考虑到年龄、性别、糖尿病、年龄(自开始透析以来的时间)、透析剂量以及血尿素氮和碳酸氢盐浓度的变化(-0.72mgdl对-0.15mgdl；P=0.001)的影响时，调整后的尿酸浓度的平均变化更为显著。在服用西维拉姆的受试者中，有23%的受试者尿酸浓度降低到-1.5 mg/dl或更高，而服用钙剂的受试者中，这一比例为10%(P=0.02)。在一项比较西维拉姆和钙基磷酸盐结合剂的随机临床试验中，西维拉姆的治疗与血清尿酸浓度的显著降低有关。
Objective. Gout affects a large fraction of persons with advanced chronic kidney disease, and hyperuricemia may increase the risk of cardiovascular disease. Several hypouricemic agents are contraindicated in patients with end-stage renal disease. Sevelamer is a nonabsorbed hydrogel that binds phosphorus and bile acids in the intestinal tract. Results of short-term and open-label studies suggest that sevelamer might lower the concentration of uric acid, another organic anion. We undertook this study to test our hypothesis that the reduction in serum uric acid concentration induced by sevelamer would be confirmed in a long-term, randomized, clinical trial comparing sevelamer with calcium-based phosphate binders.Methods. Two hundred subjects undergoing maintenance hemodialysis were randomly assigned to receive either sevelamer or calcium-based phosphorus binders in an international, multicenter, clinical trial. Data on baseline and end-of-study uric acid concentrations were available in 169 subjects (85%); the change in uric acid concentration from baseline to the end of the study was the outcome of interest.Results. Baseline clinical characteristics, including mean uric acid concentrations, were similar in subjects randomly assigned to receive sevelamer and calcium-based phosphate binders. The mean change in uric acid concentration (from baseline to the end of the study) was significantly larger in sevelamer-treated subjects (-0.64 mg/dl versus -0.26 mg/dl; P = 0.03). The adjusted mean change in uric acid concentration was more pronounced when the effects of age, sex, diabetes, vintage (time since initiation of dialysis), dialysis dose, and changes in blood urea nitrogen and bicarbonate concentrations were considered (-0.72 mg/dl versus -0.15 mg/dl; P = 0.001). Twenty-three percent of sevelamer-treated subjects experienced a study-related reduction in the concentration of uric acid equal to -1.5 mg/dl or more, compared with 10% of calcium-treated subjects (P = 0.02).Conclusion. In a randomized clinical trial comparing sevelamer and calcium-based phosphate binders, treatment with sevelamer was associated with a significant reduction in serum uric acid concentrations.