Efficacy and Safety of Tacrolimus Versus Cyclosporine in Children With Steroid-Resistant Nephrotic Syndrome: A Randomized Controlled Trial
Efficacy and Safety of Tacrolimus Versus Cyclosporine in Children With Steroid-Resistant Nephrotic Syndrome: A Randomized Controlled Trial
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DOI：
10.1053/j.ajkd.2008.11.033
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发表时间：
2009-05-01
影响因子：
13.2
通讯作者：
Dinda, Amit
中科院分区：
文献类型：
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作者：
Choudhry, Swati;Bagga, Arvind;Dinda, Amit
背景：研究他克莫司是否比环孢素A(CsA)更有效、更安全地诱导激素耐药肾病综合征(SRNS)患者的缓解。研究设计：随机对照试验，非盲，平行分组。地点和参与者：三级保健医院；连续41例特发性Spin患者，估计肾小球滤过率大于60mL/min/1.73m(2)，组织学特征显示微小病变、局灶性节段性肾小球硬化或系膜增生性肾小球肾炎，随机分为他克莫司(n=21)或CsA(n=20)治疗。干预：他克莫司(0.1~0.2 mg/kg/d)或CsA(5~6 mg/kg/d)治疗1年；隔日强的松龙与依那普利联合治疗。结果：患者完全缓解(尿蛋白/肌酐比值；0.2g/g及血清白蛋白和GT；治疗6个月和12个月时，两组患者的尿蛋白/肌酐比值分别为2.5g/dL)或部分缓解(尿蛋白/肌酐比值为0.2~2g/g，血清白蛋白：2.5g/dL)。治疗6个月后，他克莫司组18例(85.7%)缓解，CsA组16例(80%)缓解(相对危险度为1.07；95%可信区间为0.81~1.41)。12个月的缓解率也相似(RR，1.14；95%CI，0.84至1.55)。接受CsA治疗的患者复发率显著高于他克莫司(FIR，4.5；95%CI，1.1~18.2；P=0.01)。与CsA相比，他克莫司对血胆固醇水平的降幅更大(平均值差异为45.1 mg/dL；95%可信区间为19.1至71.2)。持续性肾毒性导致停药的发生率分别为4.7%和10%。美容副作用(多毛症和牙床肥大)在接受CsA治疗的患者中明显更常见(P<；0.001)。限制：单中心研究，样本量小，随访时间短。结论：他克莫司或CsA联合小剂量类固醇治疗SRNS患者具有相似的疗效。考虑到复发率较低且无美容副作用，他克莫司治疗是环孢素A的一种有前途的替代方案。Am J肾脏Dis 53：760-769。(C)2009年，由国家肾脏基金会公司提供。
Background: To examine whether tacrolimus is more effective and safe than cyclosporine (CsA) in inducing remission in patients with steroid-resistant nephrotic syndrome (SRNS).Study Design: Randomized controlled trial, nonblind, parallel group.Settings & Participants: Tertiary-care hospital; 41 consecutive patients with idiopathic SPINS, estimated glomerular filtration rate greater than 60 mL/min/1.73 m(2), and histological characteristics showing minimal change disease, focal segmental glomerulosclerosis, or mesangio-proliferative glomerulonephritis were randomly assigned to treatment with tacrolimus (n = 21) or CsA (n = 20).Intervention: Tacrolimus (0.1 to 0.2 mg/kg/d) or CsA (5 to 6 mg/kg/d) for 1 year; cotreatment with alternate-day prednisolone and enalapril.Outcomes: Patients achieving complete remission (urinary protein-creatinine ratio < 0.2 g/g and serum albumin >= 2.5 g/dL) or partial remission (urinary protein-creatinine ratio, 0.2 to 2 g/g, and serum albumin :2.5 g/dL) at 6 and 12 months; time to remission; proportion with relapses; side effects.Results: No patient was lost to follow-up. After 6 months of therapy, remission occurred in 18 (85.7%) and 16 patients (80%) treated with tacrolimus and CsA, respectively (relative risk [RR], 1.07; 95% confidence interval [CI], 0.81 to 1.41). Rates of remission at 12 months were also similar (RR, 1.14; 95% CI, 0.84 to 1.55). The proportion of patients who experienced relapse was significantly greater in those receiving CsA compared with tacrolimus (FIR, 4.5; 95% CI, 1.1 to 18.2; P = 0.01). The decrease in blood cholesterol levels was greater with tacrolimus compared with CsA (difference in mean values, 45.1 mg/dL; 95% CI, 19.1 to 71.2). Persistent nephrotoxicity necessitating stoppage of medicine was seen in 4.7% and 10% patients, respectively. Cosmetic side effects (hypertrichosis and gum hypertrophy) were significantly more frequent in CsA-treated patients (P < 0.001).Limitations: Single-center study, small sample size, and short duration of follow-up.Conclusions: Tacrolimus or CsA in combination with low-dose steroids show similar efficacy in inducing remission in patients with SRNS. Therapy with tacrolimus is a promising alternative to CsA in view of the lower risk of relapses and lack of cosmetic side effects. Am J Kidney Dis 53:760-769. (C) 2009 by the National Kidney Foundation, Inc.