他克莫司可减少血压正常的 IgA 肾病患者的蛋白尿：他克莫司治疗 IgA 肾病疗效的双盲随机对照试验。
Tacrolimus decreases albuminuria in patients with IgA nephropathy and normal blood pressure: a double-blind randomized controlled trial of efficacy of tacrolimus on IgA nephropathy.
机构信息
Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
出版信息
PLoS One. 2013 Aug 19;8(8):e71545. doi: 10.1371/journal.pone.0071545. eCollection 2013.
BACKGROUND
Treatment remains uncertain for IgA nephropathy patients with mild to moderate proteinuria, for whom anti-hypertensive medication or the RAS blocker is not applicable due to low blood pressure.
TRIAL DESIGN
A double blinded randomized trial.
METHODS
The anti-proteinuric effect of tacrolimus was explored for 40 biopsy-proven mild IgA nephropathies for 16 weeks. We randomly assigned patients either to receive tacrolimus or placebo with stratification by using a renin angiotensin system blocker. The primary outcome was the percentage change of final UACR compared to the baseline value (pcUACR).
RESULTS
The mean value of pcUACR at 12-week and 16-week visits (primary outcome) was decreased more in the Tac group compared to the control group (-52.0±26.4 vs -17.3±29.3%, p = 0.001). At each visit, pcUACR was also decreased more in the Tac group compared to the control group. In the Tac group, the pcUACRs were -60.2±28.2%, -62.2±33.9%, -48.5±29.8%, and -55.5±24.0%, and, in the control group, -6.8±32.2%, -2.5±35.9%, -12.7±34.2%, and -21.9±30.6%, at 4-week, 8-week, 12-week, and 16-week visits, respectively. The pre-defined secondary outcomes were better in the Tac group compared to the control group. The frequency of decrease in pcUACR and percentage change of UPCR (pcUPCR) ≥50% at 16 weeks were 65.0% (13/20) and 55.0% (11/20)in the Tac group, and 25.0% (5/20) and 15.0% (3/20), in the control group, respectively (p = 0.025 for pcUACR and p = 0.019 for pcUPCR). However, tacrolimus wasn't effective with a dose of 0.05 mg/kg/day in patients taking ARB. The adverse events were tolerable.
CONCLUSION
Tacrolimus effectively reduced proteinuria in IgA nephropathy with normal blood pressure. This suggested that tacrolimus could be an alternative to corticosteroid and RAS blocker for IgA nephropathy patients who cannot endure anti-hypertensive medication.
TRIAL REGISTRATION
Clinicaltrial.gov NCT1224028.
背景
对于伴有轻度至中度蛋白尿的 IgA 肾病患者，由于血压较低，抗高血压药物或肾素-血管紧张素系统阻滞剂（RAS 阻滞剂）并不适用，因此其治疗仍存在不确定性。
试验设计
一项双盲随机试验。
方法
对 40 例经活检证实的轻度 IgA 肾病患者进行为期 16 周的他克莫司的降蛋白尿作用研究。我们将患者随机分为他克莫司组或安慰剂组，并进行分层，使用 RAS 阻滞剂。主要结局是与基线值相比的最终 UACR 变化百分比（pcUACR）。
结果
12 周和 16 周随访时（主要结局），Tac 组的 pcUACR 平均值比对照组降低更多（-52.0±26.4%比-17.3±29.3%，p=0.001）。在每次就诊时，Tac 组的 pcUACR 也比对照组降低更多。在 Tac 组中，pcUACR 分别为-60.2±28.2%、-62.2±33.9%、-48.5±29.8%和-55.5±24.0%，而在对照组中，pcUACR 分别为-6.8±32.2%、-2.5±35.9%、-12.7±34.2%和-21.9±30.6%，分别在 4 周、8 周、12 周和 16 周随访时。Tac 组的预定义次要结局优于对照组。在 16 周时，pcUACR 下降和 UPCR 变化百分比（pcUPCR）≥50%的频率分别为 Tac 组 65.0%（13/20）和 55.0%（11/20），对照组为 25.0%（5/20）和 15.0%（3/20）（pcUACR 为 p=0.025，pcUPCR 为 p=0.019）。然而，在服用 ARB 的患者中，他克莫司 0.05mg/kg/天的剂量无效。不良事件可耐受。
结论
他克莫司可有效降低血压正常的 IgA 肾病患者的蛋白尿。这表明他克莫司可能是不能耐受抗高血压药物的 IgA 肾病患者的皮质类固醇和 RAS 阻滞剂的替代药物。
试验注册
Clinicaltrial.gov NCT1224028。
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