Slatopolsky E A, Burke S K, Dillon M A
Renal Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Kidney Int. 1999 Jan;55(1):299-307. doi: 10.1046/j.1523-1755.1999.00240.x.
This multicenter, open-label, dose-titration study assessed the safety and efficacy of RenaGel(R), a nonabsorbed calcium- and aluminum-free phosphate binder, in lowering serum phosphorus. Secondary outcomes were its effects on serum intact parathyroid hormone (iPTH) and serum lipids.
Phosphate binders were discontinued during a two-week washout period. Patients whose serum phosphorus was more than 6.0 mg/dl during washout were eligible for treatment. RenaGel(R), at starting doses of two, three, or four 440 mg capsules three times per day with meals, was administered to 172 hemodialysis patients for eight weeks. RenaGel(R) could be increased by one capsule per meal every two weeks as necessary to achieve serum phosphorus control. A second two-week washout period followed.
Mean serum phosphorus rose from 6.8 +/- 2.0 mg/dl at prewashout to 9.1 +/- 2.4 mg/dl at the end of the washout period. It then declined to 6.6 +/- 1.9 mg/dl by the end of the eight-week RenaGel(R) treatment period (P < 0. 0001). Serum phosphorus increased to 8.0 +/- 2.2 mg/dl at the end of the second washout period. The mean dose at the end of RenaGel(R) treatment was 5.4 g per day. Eighty-four percent of the patients previously used calcium-based phosphate binders. As expected, calcium declined during the initial washout period when calcium-based phosphate binders were discontinued. Mean serum calcium declined from 9.6 +/- 1.0 mg/dl at prewashout to 9.1 +/- 0.8 mg/dl after washout. It then increased to 9.4 +/- 0.9 mg/dl by the end of RenaGel(R) treatment. Median serum iPTH increased during the two-week washout from 208 pg/ml to 316 pg/ml and then declined to 224 pg/ml at the end of the eight-week treatment period (P < 0.0001 vs. end of initial washout). After eight weeks of treatment, RenaGel(R) reduced mean serum total cholesterol from 171.0 +/- 43.1 mg/dl to 145.0 +/- 38.7 mg/dl (P < 0.0001) and mean serum low-density lipoprotein cholesterol from 102.0 +/- 34.9 mg/dl to 75. 6 +/- 29.4 mg/dl (P < 0.0001). High-density lipoprotein cholesterol, triglycerides, and serum albumin did not change.
RenaGel(R), a novel and calcium- plus aluminum-free effective phosphate binder, can control serum phosphorus and reduce the levels of PTH and cholesterol without inducing hypercalcemia or other side effects. Thus, this new phosphate binder may be effective in the treatment of renal osteodystrophy in uremic patients.
这项多中心、开放标签、剂量滴定研究评估了一种非吸收性无钙无铝的磷结合剂RenaGel降低血清磷水平的安全性和有效性。次要结果是其对血清完整甲状旁腺激素（iPTH）和血清脂质的影响。
在为期两周的洗脱期内停用磷结合剂。洗脱期内血清磷超过6.0mg/dl的患者符合治疗条件。172例血液透析患者接受RenaGel治疗，起始剂量为每日三次，每次服用2、3或4粒440mg胶囊，随餐服用，共8周。必要时，每两周每餐可增加1粒胶囊以控制血清磷水平。随后是第二个为期两周的洗脱期。
平均血清磷在洗脱前为6.8±2.0mg/dl，洗脱期末升至9.1±2.4mg/dl。然后在为期8周的RenaGel治疗期末降至6.6±1.9mg/dl（P<0.0001）。在第二个洗脱期末，血清磷升至8.0±2.2mg/dl。RenaGel治疗期末的平均剂量为每日5.4g。84%的患者此前使用过钙基磷结合剂。正如预期的那样，在停用钙基磷结合剂的初始洗脱期内钙水平下降。平均血清钙在洗脱前为9.6±1.0mg/dl，洗脱后降至9.1±0.8mg/dl。然后在RenaGel治疗期末升至9.4±0.9mg/dl。血清iPTH中位数在两周洗脱期内从208pg/ml升至316pg/ml，然后在为期8周的治疗期末降至224pg/ml（与初始洗脱期末相比，P<0.0001）。治疗8周后，RenaGel使平均血清总胆固醇从171.0±43.1mg/dl降至145.0±38.7mg/dl（P<0.0001），平均血清低密度脂蛋白胆固醇从102.0±34.9mg/dl降至75.6±29.4mg/dl（P<0.0001）。高密度脂蛋白胆固醇、甘油三酯和血清白蛋白未发生变化。
RenaGel是一种新型的无钙无铝有效磷结合剂，可控制血清磷水平，降低PTH和胆固醇水平，且不会诱发高钙血症或其他副作用。因此，这种新型磷结合剂可能对治疗尿毒症患者的肾性骨营养不良有效。
