Lv Jicheng, Zhang Hong, Wong Muh Geot, Jardine Meg J, Hladunewich Michelle, Jha Vivek, Monaghan Helen, Zhao Minghui, Barbour Sean, Reich Heather, Cattran Daniel, Glassock Richard, Levin Adeera, Wheeler David, Woodward Mark, Billot Laurent, Chan Tak Mao, Liu Zhi-Hong, Johnson David W, Cass Alan, Feehally John, Floege Jürgen, Remuzzi Giuseppe, Wu Yangfeng, Agarwal Rajiv, Wang Hai-Yan, Perkovic Vlado
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China2The George Institute for Global Health, University of New South Wales, Sydney, Australia.
Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
JAMA. 2017 Aug 1;318(5):432-442. doi: 10.1001/jama.2017.9362.
Guidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, but the effects remain uncertain.
To evaluate the efficacy and safety of corticosteroids in patients with IgA nephropathy at risk of progression.
DESIGN, SETTING, AND PARTICIPANTS: The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study was a multicenter, double-blind, randomized clinical trial designed to recruit 750 participants with IgA nephropathy (proteinuria greater than 1 g/d and estimated glomerular filtration rate [eGFR] of 20 to 120 mL/min/1.73 m2 after at least 3 months of blood pressure control with renin-angiotensin system blockade] and to provide follow-up until 335 primary outcomes occurred.
Patients were randomized 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/d; maximum, 48 mg/d) (n = 136) or matching placebo (n = 126) for 2 months, with subsequent weaning over 4 to 6 months.
The primary composite outcome was end-stage kidney disease, death due to kidney failure, or a 40% decrease in eGFR. Predefined safety outcomes were serious infection, new diabetes, gastrointestinal hemorrhage, fracture/osteonecrosis, and cardiovascular events. The mean required follow-up was estimated to be 5 years.
After randomization of 262 participants (mean age, 38.6 [SD, 11.1] years; 96 [37%] women; eGFR, 59.4 mL/min/1.73 m2; urine protein excretion, 2.40 g/d) and 2.1 years' median follow-up, recruitment was discontinued because of excess serious adverse events. Serious events occurred in 20 participants (14.7%) in the methylprednisolone group vs 4 (3.2%) in the placebo group (P = .001; risk difference, 11.5% [95% CI, 4.8%-18.2%]), mostly due to excess serious infections (11 [8.1%] vs 0; risk difference, 8.1% [95% CI, 3.5%-13.9%]; P < .001), including 2 deaths. The primary renal outcome occurred in 8 participants (5.9%) in the methylprednisolone group vs 20 (15.9%) in the placebo group (hazard ratio, 0.37 [95% CI, 0.17-0.85]; risk difference, 10.0% [95% CI, 2.5%-17.9%]; P = .02).
Among patients with IgA nephropathy and proteinuria of 1 g/d or greater, oral methylprednisolone was associated with an increased risk of serious adverse events, primarily infections. Although the results were consistent with potential renal benefit, definitive conclusions about treatment benefit cannot be made, owing to early termination of the trial.
clinicaltrials.gov Identifier: NCT01560052.
指南推荐对患有IgA肾病且存在持续性蛋白尿的患者使用皮质类固醇，但其效果仍不确定。
评估皮质类固醇对有疾病进展风险的IgA肾病患者的疗效和安全性。
设计、地点和参与者：IgA肾病全球类固醇治疗评估（TESTING）研究是一项多中心、双盲、随机临床试验，旨在招募750名IgA肾病患者（蛋白尿大于1 g/d，且在使用肾素-血管紧张素系统阻滞剂控制血压至少3个月后，估计肾小球滤过率[eGFR]为20至120 mL/min/1.73 m²），并随访至发生335例主要结局。
患者按1:1随机分为口服甲泼尼龙组（0.6 - 0.8 mg/kg/d；最大剂量，48 mg/d）（n = 136）或匹配的安慰剂组（n = 126），为期2个月，随后在4至6个月内逐渐减量。
主要复合结局为终末期肾病、肾衰竭死亡或eGFR下降40%。预定义的安全结局为严重感染、新发糖尿病、胃肠道出血、骨折/骨坏死和心血管事件。估计平均所需随访时间为5年。
在随机分配262名参与者（平均年龄38.6[标准差，11.1]岁；96名[37%]女性；eGFR为59.4 mL/min/1.73 m²；尿蛋白排泄量为2.40 g/d）并进行2.1年的中位随访后，由于严重不良事件过多，研究停止。甲泼尼龙组有20名参与者（14.7%）发生严重事件，而安慰剂组有4名（3.2%）（P = 0.001；风险差异，11.5%[95%置信区间，4.8% - 18.2%]），主要是由于严重感染过多（11名[8.1%]对0名；风险差异，8.1%[95%置信区间，3.5% - 13.9%]；P < 0.001），包括2例死亡。主要肾脏结局在甲泼尼龙组8名参与者（5.9%）中发生，而在安慰剂组20名（15.9%）中发生（风险比，0.37[95%置信区间，0.17 - 0.85]；风险差异，10.0%[95%置信区间，2.5% - 17.9%]；P = 0.02）。
在患有IgA肾病且蛋白尿为1 g/d或更高的患者中，口服甲泼尼龙与严重不良事件风险增加相关，主要是感染。尽管结果与潜在的肾脏获益一致，但由于试验提前终止，无法得出关于治疗获益的确切结论。
clinicaltrials.gov标识符：NCT01560052。
