Department of Nephrology, University Hospital of the RWTH Aachen, Pauwelsstase 30, Aachen, Germany.
Nephrol Dial Transplant. 2010 Aug;25(8):2672-9. doi: 10.1093/ndt/gfq053. Epub 2010 Feb 18.
Cardiovascular morbidity and mortality are massively increased in patients with chronic kidney disease (CKD). Sevelamer hydrochloride has been shown to attenuate cardiovascular calcifications in CKD and end-stage renal disease (ESRD) patients. We assessed how sevelamer hydrochloride influences the evolution of serum fetuin-A and other serological factors predicting cardiovascular outcome and survival in haemodialysis patients.
Fifty-seven prevalent haemodialysis patients were included in a three-phase prospective interventional trial (A-B-A design; 8 weeks per phase). Sevelamer was only administered in the middle phase of the study. Within the other two phases, >or=90% of the patients received calcium acetate for phosphate binding. Detailed time courses of serum biochemistries were analysed in order to obtain detailed insight into the influence of sevelamer upon CKD-mineral and bone disorder (MBD) parameters as well as serum fetuin-A, fibroblast growth factor 23 (FGF23) and uraemic toxin levels [uric acid, indoxyl sulphate, hippuric acid, indole acetic acid, p-cresol and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF)].
Forty-one patients finished the three prospective study phases (intention-to-treat analysis). After treatment with sevelamer, serum fetuin-A significantly increased (+21%), showing a delayed increase outlasting the third (non-sevelamer) study period. Total and low-density lipoprotein (LDL) cholesterol levels, as well as serum calcium, decreased significantly. The opposite occurred with albumin, C-reactive protein and intact parathyroid hormone (iPTH). FGF23, uric acid, indoxyl sulphate, hippuric acid, indole acetic acid, CMPF and serum phosphate did not change significantly during sevelamer treatment. In contrast, in parallel to sevelamer treatment, there was a significant rise in serum P-cresol.
In haemodialysis patients, treatment with sevelamer over 8 weeks was associated with a delayed yet long-lasting increase in serum fetuin-A levels. Increasing the serum level of fetuin-A, a negative acute-phase protein and systemic calcification inhibitor, might be one of the potential anti-calcification mechanisms of sevelamer. Since we failed to detect a decrease in systemic inflammation and uraemic toxins, the exact mechanisms by which sevelamer treatment affects serum fetuin-A remain to be determined.
慢性肾脏病（CKD）患者的心血管发病率和死亡率大大增加。盐酸司维拉姆已被证明可减轻 CKD 和终末期肾病（ESRD）患者的心血管钙化。我们评估了盐酸司维拉姆如何影响血清胎球蛋白 A 及其他预测心血管结局和血液透析患者生存的血清因素的演变。
57 例现患血液透析患者纳入一项三阶段前瞻性干预试验（A-B-A 设计；每个阶段 8 周）。仅在研究的中间阶段给予盐酸司维拉姆。在其他两个阶段，>90%的患者接受醋酸钙以结合磷酸盐。分析血清生化的详细时间过程，以便深入了解盐酸司维拉姆对 CKD-矿物质和骨代谢紊乱（MBD）参数以及血清胎球蛋白 A、成纤维细胞生长因子 23（FGF23）和尿毒症毒素水平[尿酸、吲哚硫酸、马尿酸、吲哚乙酸、对甲酚和 3-羧基-4-甲基-5-丙基-2-呋喃丙酸（CMPF）]的影响。
41 例患者完成了三项前瞻性研究阶段（意向治疗分析）。用盐酸司维拉姆治疗后，血清胎球蛋白 A 显著增加（+21%），且增加持续时间超过第三（非司维拉姆）研究期。总胆固醇和低密度脂蛋白（LDL）胆固醇以及血清钙水平显著降低。白蛋白、C 反应蛋白和完整甲状旁腺激素（iPTH）则相反。用盐酸司维拉姆治疗期间，FGF23、尿酸、吲哚硫酸、马尿酸、吲哚乙酸、CMPF 和血清磷酸盐无明显变化。相反，与盐酸司维拉姆治疗同时，血清对甲酚显著升高。
在血液透析患者中，用盐酸司维拉姆治疗 8 周以上与血清胎球蛋白 A 水平的延迟但持久增加相关。增加胎球蛋白 A（一种负急性期蛋白和全身性钙化抑制剂）的血清水平可能是盐酸司维拉姆的潜在抗钙化机制之一。由于我们未能检测到全身炎症和尿毒症毒素的减少，盐酸司维拉姆治疗影响血清胎球蛋白 A 的具体机制仍有待确定。
