Patel Leena, Bernard Lisa M, Elder Grahame J
Cornerstone Research Group, Burlington, Ontario, Canada;
Department of Renal Medicine, Westmead Hospital, Westmead, New South Wales, Australia; and Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, Sydney, Australia
Clin J Am Soc Nephrol. 2016 Feb 5;11(2):232-44. doi: 10.2215/CJN.06800615. Epub 2015 Dec 14.
People with CKD stages 3-5 and on dialysis (5D) have dramatically increased mortality, which has been associated with hyperphosphatemia in many studies. Oral phosphate binders are commonly prescribed to lower serum phosphate. We conducted an updated meta-analysis of the noncalcium-based binder (non-CBB) sevelamer versus CBBs in CKD stages 3-5D.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Randomized, controlled trials comparing sevelamer with CBBs were identified through MEDLINE and the Cochrane Central Register of Controlled Trials. Patient-level outcomes included all-cause mortality, cardiovascular events and mortality, hospitalization, and adverse effects. Intermediate outcomes included vascular calcification and bone changes. Biochemical outcomes included serum phosphate, calcium, parathyroid hormone, lipids, and hypercalcemia. We conducted and reported this review according to Cochrane guidelines.
We included 25 studies to March 31, 2015 with 4770 participants (88% on hemodialysis). Patients receiving sevelamer had lower all-cause mortality (risk ratio [RR], 0.54; 95% confidence interval [95% CI], 0.32 to 0.93), no statistically significant difference in cardiovascular mortality (n=2712; RR, 0.33; 95% CI, 0.07 to 1.64), and an increase in combined gastrointestinal events of borderline statistical significance (n=384; RR, 1.42; 95% CI, 0.97 to 2.08). For biochemical outcomes, patients receiving sevelamer had lower total serum cholesterol (mean difference [MD], -20.2 mg/dl; 95% CI, -25.9 to -14.5 mg/dl), LDL-cholesterol (MD, -21.6 mg/dl; 95% CI, -27.9 to -15.4 mg/dl), and calcium (MD, -0.4 mg/dl; 95% CI, -0.6 to -0.2 mg/dl) and a reduced risk of hypercalcemia (RR, 0.30; 95% CI, 0.19 to 0.48). End of treatment intact parathyroid hormone was significantly higher for sevelamer (MD, 32.9 pg/ml; 95% CI, 0.1 to 65.7 pg/ml). Serum phosphate values showed no significant differences.
Patients with CKD stages 3-5D using sevelamer have lower all-cause mortality compared with those using CBBs. Because of a lack of placebo-controlled studies, questions remain regarding phosphate binder benefits for patients with CKD stages 3-5 and not on dialysis.
慢性肾脏病3 - 5期及接受透析（5D）的患者死亡率显著增加，许多研究表明这与高磷血症有关。口服磷结合剂常用于降低血清磷水平。我们对非钙基结合剂（非CBB）司维拉姆与慢性肾脏病3 - 5D期患者使用的钙基结合剂（CBBs）进行了一项更新的荟萃分析。
设计、地点、参与者及测量指标：通过MEDLINE和Cochrane对照试验中央注册库确定了比较司维拉姆与CBBs的随机对照试验。患者层面的结局包括全因死亡率、心血管事件及死亡率、住院率和不良反应。中间结局包括血管钙化和骨骼变化。生化结局包括血清磷、钙、甲状旁腺激素、血脂和高钙血症。我们按照Cochrane指南进行并报告了本综述。
截至2015年3月31日，我们纳入了25项研究，共4770名参与者（88%接受血液透析）。接受司维拉姆治疗的患者全因死亡率较低（风险比[RR]，0.54；95%置信区间[95%CI]，0.32至0.93），心血管死亡率无统计学显著差异（n = 2712；RR，0.33；95%CI，0.07至1.64），合并胃肠道事件有边缘统计学意义的增加（n = 384；RR，1.42；95%CI，0.97至2.08）。对于生化结局，接受司维拉姆治疗的患者总血清胆固醇较低（平均差[MD]，-20.2mg/dl；95%CI，-25.9至-14.5mg/dl），低密度脂蛋白胆固醇（MD，-21.6mg/dl；95%CI，-27.9至-15.4mg/dl），钙（MD，-0.4mg/dl；95%CI，-0.6至-0.2mg/dl），高钙血症风险降低（RR，0.30；95%CI，0.19至0.48）。治疗结束时，司维拉姆组的完整甲状旁腺激素显著更高（MD，32.9pg/ml；95%CI，0.1至65.7pg/ml）。血清磷值无显著差异。
与使用CBBs的慢性肾脏病3 - 5D期患者相比，使用司维拉姆的患者全因死亡率更低。由于缺乏安慰剂对照研究，对于未接受透析的慢性肾脏病3 - 5期患者使用磷结合剂的益处仍存在疑问。
