骨化三醇口服或静脉给药联合西那卡塞治疗维持性血液透析患者继发性甲状旁腺功能亢进症的疗效观察

Oral or intravenous calcitriol combined with cinacalcet in the treatment of secondary hyperparathyroidism in maintenance hemodialysis patients

目的比较尿毒症维持性血液透析患者继发性甲状旁腺功能亢进症(secondary hyperparathyroidism, SHPT)口服或静脉注射骨化三醇联合西那卡塞治疗的效果及安全性。方法维持性血液透析3个月以上SHPT患者50例,根据血清甲状旁腺激素(parathormone, PTH)水平分为轻度组(PTH 300~600 ng/L)29例和中重度组(PTH>600 ng/L)21例;再根据骨化三醇给药方式,轻度组分为口服亚组16例、静脉亚组13例,中重度组分为口服亚组12例、静脉亚组9例。轻、中重度组均给予盐酸西那卡塞餐中吞服,初始剂量均为25 mg/d;轻、中重度组口服及静脉亚组骨化三醇初始剂量分别为1~2μg/次、2~4μg/次,均2次/周;之后各组根据血钙和患者耐受情况调整西那卡塞、骨化三醇剂量,每2~4周调整1次,西那卡塞最大剂量为100 mg/d,骨化三醇最大剂量为6μg/d。分别于治疗前及治疗3、6个月采集透析前空腹静脉血,检测血钙、血磷、PTH、碱性磷酸酶(alkaline phosphatase, ALP)水平;记录西那卡塞、骨化三醇使用剂量;比较治疗期间不良反应发生率。结果轻度组口服、静脉亚组治疗前及治疗3、6个月血清PTH水平在组间比较差异有统计学意义(P<0.05),静脉亚组治疗后3个月血磷水平[(2.97±0.57)mmol/L]较治疗前[(2.71±0.49)mmol/L]增高(P<0.05),且高于口服亚组[(2.02±0.39)mmol/L](P<0.05),治疗后6个月血清PTH水平[(128.93±61.23)ng/L]较口服组[(244.74±39.31)ng/L]降低(P<0.05)。中重度组口服、静脉亚组治疗前及治疗3、6个月血清PTH、ALP水平在组间比较差异有统计学意义(P<0.05);静脉亚组治疗3、6个月血清PTH水平[(386.67±89.84)、(177.88±68.63)ng/L]较治疗前[(868.45±189.66)ng/L]降低,治疗6个月ALP水平[(66.25±27.39)u/L]较治疗前[(151.58±85.11)u/L]、治疗3个月[(109.90±49.92) u/L]降低(P<0.05),且治疗6个月血清PTH水平较口服亚组[(300.23±63.01)ng/L]明显降低(P<0.05);口服亚组治疗6个月PTH水平较治疗前[(654.00±96.00)ng/L]降低(P<0.05)。轻、中重度组口服亚组治疗3、6个月西那卡塞剂量、治疗前及治疗3、6个月骨化三醇使用剂量与静脉亚组比较差异均无统计学意义(P>0.05);中重度组静脉亚组治疗6个月骨化三醇剂量较治疗前、治疗3个月均显著降低(P<0.05)。轻度组口服和静脉亚组均无不良反应发生;中重度组口服亚组2例、静脉亚组1例出现轻度恶心、上腹不适等消化道反应,2亚组不良反应发生率比较差异无统计学意义(P>0.05)。结论西那卡塞联合骨化三醇注射液治疗轻、中重度SHPT均具有较好的效果;中重度SHPT联合静脉用骨化三醇可能减少药物剂量,同时改善骨代谢状态。

Objective To compare the efficacy and safety of oral and intravenous calcitriol combined with cinacalcet in the treatment of secondary hyperparathyroidism(SHPT)in maintenance hemodialysis patients.Methods Fifty patients with SHPT undergoing maintenance hemodialysis for more than 3 months were divided into 29 patients with parathyroid hormone(PTH)of 300 to 600 ng/L(mild group)and 21 patients with PTH≥600 ng/L(moderate/severe group).Mild group was redivided into 16 patients receiving oral calcitriol(mild oral subgroup)and 13 patients receiving intravenous calcitriol(mild intravenous subgroup).Moderate/severe group was redivided into 12 patients receiving oral calcitriol(moderate/severe oral subgroup)and 9 patients receiving intravenous calcitriol(moderate/severe intravenous subgroup).Cinacalcet was given with meals at an initial dose of 25 mg/d,while calcitriol was initially given 1 to 2μg each time in mild group and 2 to 4μg each time in moderate/severe group,twice per 2 week.The doses of cinacalcet and calcitriol were adjusted once every 2 to 4 weeks according to the serum calcium level and the patient’s tolerance,with the maximum cinacalcet and calcitriol doses of 100 mg/d and 6μg/d.The fasting levels of serum calcium,phosphorus,PTH and alkaline phosphatase were detected before treatment,and after 3-and 6-month treatment.The doses of cinacalcet and calcitriol were recorded.The incidence of adverse reactions during treatment was compared.Results The PTH level showed a significant difference between mild oral and intravenous subgroups before treatment and after 3-and 6-month treatment(P<0.05).The blood phosphorus level was higher after 3-month treatment((2.97±0.57)mmol/L)than that before treatment((2.71±0.49)mmol/L)in mild intravenous subgroup,higher than that in mild oral subgroup((2.02±0.39)mmol/L)(P<0.05).The PTH level was lower after 6-month treatment in mild intravenous subgroup((128.93±61.23)ng/L)than that in mild oral subgroup((244.74±39.31)ng/L)(P<0.05).The levels of PTH and alkaline phosphatase showed significant differences between moderate/severe oral and intravenous subgroups(P<0.05).The level of PTH was lower after 3-month treatment((386.67±89.84)ng/L)and after 6-month treatment((177.88±68.63)ng/L)than that before treatment((868.45±189.66)ng/L),and the level of alkaline phosphatase was lower after6-month treatment((66.25±27.39)u/L)than that before treatment((151.58±85.11)u/L)and after 3-month treatment((109.90±49.92)u/L)in moderate/severe intravenous subgroup(P<0.05).The level of PTH was lower after 6-month treatment in moderate/severe intravenous subgroup than that in moderate/severe oral subgroup((300.23±63.01)ng/L)(P<0.05),and was lower after 6-month treatment than that before treatment((654.00±96.00)ng/L)in moderate/severe oral subgroup(P<0.05).The doses of cinacalcet and calcitriol showed no significant differences between oral subgroups and intravenous subgroups(P>0.05).The dose of calcitriol was lower after 6-month treatment than that before treatment and after 3-month treatment in moderate/severe intravenous subgroup(P<0.05).No adverse reactions were found in mild oral and intravenous subgroups.The adverse reactions showed no significant difference between moderate/severe oral subgroup(2 cases of slight nausea and upper abdominal discomfort)and moderate/severe intravenous subgroup(1 case of slight nausea and upper abdominal discomfort)(P>0.05).Conclusion The combination of cinacalcet and calcitriol injection has a good efficacy on both mild and moderate/severe SHPT,and it can reduce the drug dose and improve bone metabolism for moderate/severe SHPT.