Shanghai Ruijin Hospital, Shanghai, China.
Nephrol Dial Transplant. 2014 Jan;29(1):152-60. doi: 10.1093/ndt/gft232. Epub 2013 Oct 22.
Hyperphosphataemia in patients with advanced chronic kidney disease (CKD) is associated with adverse outcomes, including vascular calcification and higher mortality rates. While phosphate lowering is an integral aspect of CKD management, the efficacy and safety of phosphate binders in a contemporary cohort of Chinese haemodialysis patients (who have different genetics and dietary patterns than other populations) has not been previously described. Moreover, sparse data are available on strategies for optimal dose titration when transitioning from a calcium-based to a polymer-based phosphate binder.
This randomized, double-blind, dose-titration study compared sevelamer carbonate (starting dose 800 mg three times daily) with placebo over 8 weeks' duration in Chinese CKD patients on haemodialysis. Patients were required to be using calcium-based binders prior to study start.
In all, 205 patients were randomized (sevelamer, n = 135; placebo, n = 70); mean age was 48.6 years, 61% were male and the mean time on dialysis was 4.4 years. The mean serum phosphorus decreased significantly in patients treated with sevelamer carbonate [change -0.69 ± 0.64 mmol/L (-2.14 ± 1.98 mg/dL)] but remained persistently elevated with placebo [change -0.06 ± 0.57 mmol/L (-0.19 ± 1.76 mg/dL)] (P < 0.0001). When compared with placebo, sevelamer carbonate treatment resulted in statistically significant greater mean reductions from baseline in serum total (-17.1 versus -3.3%) and low-density lipoprotein cholesterol (-33.5 versus-7.6%) (P < 0.0001 for both). Sevelamer carbonate was well tolerated with 96% adherence compared with 97% adherence in the placebo arm. Overall, adverse events experienced by patients in the sevelamer carbonate and placebo treatment groups were similar and consistent with their underlying renal disease.
This study demonstrated that hyperphosphataemia developed quickly following the cessation of phosphate binders and remained persistently elevated in end-stage CKD in the placebo-treated group. Gradually titrating up sevelamer carbonate from an initial dose of 2.4 g/day to an average daily dose of 7.1 ± 2.5 g/day was well tolerated, safe and efficacious in contemporary Chinese haemodialysis patients.
晚期慢性肾脏病（CKD）患者的高磷血症与不良结局相关，包括血管钙化和更高的死亡率。虽然降低磷是 CKD 管理的一个重要方面，但在以前的研究中，尚未描述不同遗传和饮食模式的中国血液透析患者（与其他人群相比）中使用磷结合剂的疗效和安全性。此外，当从碳酸钙基磷结合剂转换为聚合物基磷结合剂时，关于最佳剂量滴定策略的数据很少。
这项随机、双盲、剂量滴定研究比较了碳酸司维拉姆（起始剂量 800mg，每日 3 次）与安慰剂在 8 周内对正在接受血液透析的中国 CKD 患者的疗效。患者在研究开始前需要使用碳酸钙基结合剂。
共有 205 名患者被随机分组（碳酸司维拉姆组，n=135；安慰剂组，n=70）；平均年龄为 48.6 岁，61%为男性，透析时间平均为 4.4 年。接受碳酸司维拉姆治疗的患者血清磷显著降低[变化-0.69±0.64mmol/L（-2.14±1.98mg/dL）]，而安慰剂组持续升高[变化-0.06±0.57mmol/L（-0.19±1.76mg/dL）]（P＜0.0001）。与安慰剂相比，碳酸司维拉姆治疗组从基线开始的血清总胆固醇（-17.1%对-3.3%）和低密度脂蛋白胆固醇（-33.5%对-7.6%）的平均降幅更大，且差异有统计学意义（均 P＜0.0001）。碳酸司维拉姆的依从性为 96%，与安慰剂组的 97%相似。总的来说，碳酸司维拉姆治疗组和安慰剂组患者的不良反应与他们的基础肾脏疾病相似且一致。
这项研究表明，停止使用磷结合剂后，高磷血症很快发展，并在安慰剂治疗组的终末期 CKD 中持续升高。逐渐将碳酸司维拉姆从起始剂量 2.4g/天滴定至平均 7.1±2.5g/天的剂量，在当代中国血液透析患者中耐受性良好、安全且有效。
