泼尼松龙高剂量单用及低剂量联用他克莫司治疗成人微小病变肾病综合征的疗效和安全性分析

Analysis of the efficacy and safety of the therapy of high dose prednisolone alone and the therapy of low dose prednisolone combined with tacrolimus in the treatment of adult minimal change nephrotic syndrome

目的 探讨泼尼松龙高剂量单用及低剂量联用他克莫司治疗成人微小病变肾病综合征(minimal change nephrotic syndrome,MCNS)的疗效和安全性。方法 选取我院2019年12月—2021年12月住院的成人MCNS患者120例,进行为期24周的双盲随机平行对照试验(实验组和对照组各60例),治疗方法为:治疗组0.05 mg/(kg·次)(每天2次)他克莫司联合0.5 mg/(kg·次)(每天1次)泼尼松龙,对照组1 mg/(kg·次)(每天1次)泼尼松龙,长达8周或直至达到完全缓解。完全缓解2周后,将两组的泼尼松龙逐渐减少至维持剂量5~7.5 mg/d,直至24周。主要终点是8周内完全缓解(尿蛋白肌酐比,UPCR<0.2 g/g);次要终点包括完全缓解至24周内缓解的时间,复发率(蛋白尿和UPCR>3.0 g/g)和不良事件。结果 治疗组8周内完全缓解率80.0%(48/60,中位时间15 d,95%CI 14~27),对照组8周内完全缓解率76.7%(46/60,中位时间16 d,95%CI 14~28),两组间差异无统计学意义(χ^(2)=0.462,P=0.639)。治疗组复发率5.0%(3/60),对照组复发率21.7%(13/60),两组间差异有统计学意义(χ^(2)=18.722,P <0.001)。在24周的随访过程中出现不良事件治疗组有19例(31.7%),对照组有37例(61.7%),治疗组发生率显著低于对照组(χ^(2)=14.583,P <0.001)。结论 在成人MCNS患者的临床缓解中,他克莫司和低剂量泼尼松龙联合治疗不劣于单用高剂量泼尼松龙治疗,且联合治疗比单用高剂量泼尼松龙治疗可降低MCNS复发率和不良事件的发生率。

Objective To compare the efficacy and safety of the therapy of high-dose prednisolone alone and the therapy of tacrolimus combined with low-dose prednisolone in the treatment of adults with minimal change nephrotic syndrome(MCNS).Methods A total of 120 adult MCNS patients hospitalized in General Hospital of Eastern Warfare Zone from December 2019 to December 2021 were selected for a 24-week double-blind randomized parallel controlled trial(60 patients in each group of the experimental group and the control group).The patients in the experimental group received 0.05 mg/(kg·time)(twice a day) tacrolimus combined with0.5 mg/(kg·time)(once a day) prednisolone,and the patients in the control group received 1 mg/(kg·time)(once a day) prednisolone,for up to 8 weeks or until complete remission.After two weeks of complete remission,the prednisolone of the two groups was gradually reduced to a maintenance dose of 5-7.5 mg/d until 24 weeks after study initiation.The primary endpoint was complete remission(urinary protein:creatinine ratio 0.2 g/g) within 8weeks.Secondary endpoints included the time from complete remission to remission within 24 weeks after the start of the study,recurrence rate(proteinuria and urinary protein:creatinine ratio 3.0 g/g),and adverse events.Results Among patients receiving tacrolimus combined with low-dose prednisolone,the rate of the patients achieved a complete response was 48/60 within 8 weeks [80.0%,median time 15 days(95% CI,14 to 27)].Among patients receiving high-dose prednisolone,the rate of the patients achieved a complete response was 46/60 within8 weeks[76.7%,median time 16 days(95% CI,14 to 28)].There was no significantly statistical difference between the two groups( χ^(2)= 0.462,P = 0.639).The recurrence rate was 3/60(5.0%) in the patients who received the therapy of tacrolimus combined low-dose prednisolone,and that was 13/60(21.7%) in the patients who received the therapy of high-dose prednisolone,so there was a significant difference between the two groups( χ^(2)=18.722,P<0.001).During the 24-week follow-up,19 patients(31.7%) occured adverse events in the tacrolimus plus low-dose prednisolone group.37 Patients(61.7%) occured adverse events in the high-dose prednisolone group,and the incidence of adverse events in the tacrolimus combined with low-dose prednisolone group was significantly lower than that in the high-dose prednisolone group( χ^(2)= 14.583,P<0.001).Conclusion Combination therapy of tacrolimus and low-dose prednisolone was noninferior to high-dose prednisolone therapy in clinical remission in adult patients with MCNS,and the therapy of tacrolimus combined with low-dose prednisolone could significantly reduce the rate of recurrence and adverse events of the patients with MCNS,compared with the therapy of high-dose prednisolone(P<0.001).