环磷酰胺联合糖皮质激素治疗特发性膜性肾病的疗效和预测因素分析

Predictive factors of response to steroids and cyclophosphamide therapy in idiopathic membranous nephropathy

目的评估环磷酰胺（CTX）冲击联合糖皮质激素治疗特发性膜性肾病（IMN）患者的疗效，分析治疗早期临床相关指标对治疗后缓解或复发的预测价值。方法采用回顾性队列研究的方法。人选2011年01月01日至2013年12年31日上海交通大学医学院附属仁济医院（东院）肾脏科经肾活检确诊的IMN患者，接受≥6个月的口服糖皮质激素联合静脉CTX冲击治疗。分析患者基线、治疗3个月血、尿生化指标与疗效的相关关系，评估各指标对于治疗后缓解和复发的预测价值。结果83例患者入选本研究。中位随访时间为20（12，30）个月。至随访终点有80．7％（67／83）的患者达到缓解，47．0％（39／83）的患者达到完全缓解（CR）。多因素Cox回归分析提示：基线尿蛋白量、治疗3个月尿蛋白量相对于基线值下降率是IMN患者缓解（P〈0．001）和完全缓解（P〈0．001）的独立预测因素。规律随访的患者中，25．9％（14／54）的患者复发。部分缓解是影响IMN患者复发的独立危险因素（HR：40．918，95％CI：5．023—333．355，P=0．001）。部分缓解患者的复发风险是完全缓解者的40．92倍。最常见的不良反应为感染（25／83）和肝酶（5／83）升高，2例（2／83）的患者出现恶性肿瘤。结论基线尿蛋白排泄率和治疗3个月尿蛋白量下降率可以预测静脉环磷酰胺冲击联合口服糖皮质激素治疗IMN的疗效。部分缓解与IMN复发独立相关。

Objectives To investigate demographic and clinical factors which could be predictive of clinical remission or relapse in patients with idiopathic membranous nephropathy treated with oral steroids and iv cyclophosphamide therapy. Methods This was a retrospective cohort study where a total of 83 patients with biopsy- proven IMN who had received oral prednisone and iv cyclophosphamide for at least 6 months were enrolled. Demographic and clinical factors of these patients were analyzed at baseline and three months after the initiation of therapy to evaluate their respective effects upon clinical remission and relapse. Results Median follow-up duration was 20 （12-30） months. At the end of follow-up, 80.7% （67/83） of the patients attained remission and 47.0% 09/83） attained complete remission （CR）. The amount of proteinuria at baseline and the reduction rate of proteinuria three months after treatment predicted clinical remission and CR. 54 patients in the remission group were followed up to the endpoint and 14 of them relapsed with nephroticsyndrome. The presence of a PR versus CR significantly predicted relapse （HR： 40.198, 95%CI： 5.023-333.355, P= 0.001）. Infection was the most common adverse event. Two patients developed malignancies after onset of cyclophosphamide treatment. Conclusions A high rate of good response and a relatively low rate of adverse events were observed in this study. Baseline proteinuria and reduction rate of proteinuria 3 months after onset of eyclophosphamide regimen were independent predictive factors of response. Compared with CR, PR was predictive of a high probability of relapse.