Intensive Supportive Care plus Immunosuppression in IgA Nephropathy
Intensive Supportive Care plus Immunosuppression in IgA Nephropathy
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DOI：
10.1056/nejmoa1415463
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发表时间：
2015-12-03
影响因子：
158.5
通讯作者：
Floege, Juergen
中科院分区：
文献类型：
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作者：
Rauen, Thomas;Eitner, Frank;Floege, Juergen
背景在 IgA 肾病患者中加入支持治疗后，免疫抑制治疗的结果尚不确定。方法我们采用两组、平行、组序设计进行了一项多中心、开放、随机、对照试验。在6个月的磨合期，根据蛋白尿情况调整支持治疗（特别是阻断肾素-血管紧张素系统）。持续性蛋白尿且尿蛋白排泄量至少为 0.75 g/天的患者被随机分配接受单独支持治疗（支持治疗组）或支持治疗加免疫抑制治疗（免疫抑制组），为期 3 年。按层次顺序排列的主要终点是试验结束时的完全临床缓解（蛋白质与肌酐比值 < 0.2 [蛋白质和肌酐均以克为单位]，估计肾小球滤过率 [eGFR] 相对于基线每分钟每 1.73 m(2) 下降 < 5 ml），以及试验结束时 eGFR 至少每分钟每 1.73 m(2) 下降 15 ml。审判。使用逻辑回归模型分析主要终点。结果 337 名患者中的 309 名完成了磨合阶段。 94 名患者的蛋白尿水平降至每天尿蛋白排泄量低于 0.75 克。其余 162 名同意接受随机分组的患者中，80 名被分配到支持治疗组，82 名被分配到免疫抑制组。 3 年后，支持治疗组有 4 名患者 (5%) 达到临床完全缓解，而免疫抑制组有 14 名患者 (17%)（P = 0.01）。支持治疗组中共有 22 名患者 (28%) 和免疫抑制组中有 21 名患者 (26%) 的 eGFR 降低至少 15 ml/min/1.73 m(2) (P = 0.75)。两组之间 eGFR 的年度下降没有显着差异。与支持治疗组相比，免疫抑制组中有更多患者在治疗第一年出现严重感染、糖耐量受损和体重增加超过 5 公斤。免疫抑制组有1例患者死于脓毒症。结论高危IgA肾病患者在强化支持治疗的基础上加用免疫抑制治疗并没有显着改善预后，并且在3年的研究阶段，接受免疫抑制治疗的患者观察到更多的不良反应，而eGFR下降率没有变化。 （由德国联邦教育和研究部资助；STOP-IgAN ClinicalTrials.gov 编号，NCT00554502。）
BACKGROUNDThe outcomes of immunosuppressive therapy, when added to supportive care, in patients with IgA nephropathy are uncertain.METHODSWe conducted a multicenter, open-label, randomized, controlled trial with a two-group, parallel, group-sequential design. During a 6-month run-in phase, supportive care (in particular, blockade of the renin-angiotensin system) was adjusted on the basis of proteinuria. Patients who had persistent proteinuria with urinary protein excretion of at least 0.75 g per day were randomly assigned to receive supportive care alone (supportive-care group) or supportive care plus immunosuppressive therapy (immunosuppression group) for 3 years. The primary end points in hierarchical order were full clinical remission at the end of the trial (protein-to-creatinine ratio < 0.2 [with both protein and creatinine measured in grams] and a decrease in the estimated glomerular filtration rate [eGFR] of < 5 ml per minute per 1.73 m(2) of body-surface area from baseline) and a decrease in the eGFR of at least 15 ml per minute per 1.73 m(2) at the end of the trial. The primary end points were analyzed with the use of logistic-regression models.RESULTSThe run-in phase was completed by 309 of 337 patients. The proteinuria level decreased to less than 0.75 g of urinary protein excretion per day in 94 patients. Of the remaining 162 patients who consented to undergo randomization, 80 were assigned to the supportive-care group, and 82 to the immunosuppression group. After 3 years, 4 patients (5%) in the supportive-care group, as compared with 14 (17%) in the immunosuppression group, had a full clinical remission (P = 0.01). A total of 22 patients (28%) in the supportive-care group and 21 (26%) in the immunosuppression group had a decrease in the eGFR of at least 15 ml per minute per 1.73 m(2) (P = 0.75). There was no significant difference in the annual decline in eGFR between the two groups. More patients in the immunosuppression group than in the supportive-care group had severe infections, impaired glucose tolerance, and weight gain of more than 5 kg in the first year of treatment. One patient in the immunosuppression group died of sepsis.CONCLUSIONSThe addition of immunosuppressive therapy to intensive supportive care in patients with high-risk IgA nephropathy did not significantly improve the outcome, and during the 3-year study phase, more adverse effects were observed among the patients who received immunosuppressive therapy, with no change in the rate of decrease in the eGFR. (Funded by the German Federal Ministry of Education and Research; STOP-IgAN ClinicalTrials.gov number, NCT00554502.)