IgG排泄分数对特发性膜性肾病药物反应性预测的临床研究

Clinical research of fractional excretion of IgG on predicting drug responsiveness in patients with idiopathic membranous nephropathy

目的探讨IgG排泄分数(FEIgG)对特发性膜性肾病(IMN)患者药物反应性及病情缓解的预测意义。方法回顾性分析2014年4月至2017年8月本院经临床及病理资料确诊并定期随访的IMN患者82例,利用ROC曲线确定预测临床缓解时间的FEIgG界值,对比基线不同FEIgG水平临床缓解时间的差别,分析不同FEIgG水平对免疫抑制治疗(他克莫司或环磷酰胺)及支持治疗的药物反应性的影响。结果绘制e GFR、24 h尿蛋白定量及FEIgG预测临床缓解时间的ROC曲线,曲线下面积(AUC)分别为0.509、0.701、0.948;确定FEIgG界值为0.029,所有患者分为高水平组(FEIgG>0.029)、低水平组(FEIgG<0.029);接受治疗前,两组患者性别、年龄、平均动脉压及eGFR差异均无统计学意义(P>0.05),两组间FEIgG、24 h尿蛋白定量、血清白蛋白差异有统计学意义(P<0.05);两组临床缓解时间分别为(18.75±6.81)个月、(8.46±3.74)个月,差异有统计学意义(P<0.001)。FEIgG低水平免疫抑制治疗组与FEIgG低水平支持治疗组缓解时间比较差异无统计学意义(P=0.265),二者均低于FEIgG高水平免疫抑制治疗组(P<0.001);FEIgG高水平组中他克莫司组较环磷酰胺组缓解时间缩短,但差异无统计学意义(P=0.131);FEIgG高、低水平组间他克莫司治疗缓解时间比较差异有统计学意义(t=6.734,P<0.001);电镜下,FEIgG高水平组足突广泛融合及足细胞弥漫空泡变性比例均较低水平组高,差异有统计学意义(P<0.001)。结论FEIgG可作为预测IMN患者药物反应性及病情缓解的临床指标,对早期识别高危患者及制定临床决策至关重要,高FEIgG患者早期开始免疫抑制治疗可能获益更大。

Objective To explore the predictive value of fractional excretion of IgG(FEIgG)on drug responsiveness and remission in patients with idiopathic membranous nephropathy(IMN).Methods Retrospective analysis of 82 patients with IMN diagnosed by clinical and pathological data and regularly followed up from April 2014 to August 2017.Receiver operating characteristic(ROC)curve was used to determine the FE IgG threshold.Comparing the difference of remission time under different baseline levels of FE IgG,and analyzing the effect of different levels of FEIgG on the drug responsiveness of immunosuppressive therapy(tacrolimus or cyclophosphamide)and supportive therapy.Results Areas under the curve(AUC)of estimated glomerular filtration rate(eGFR),24-hour urinary protein quantity and FE IgG were 0.509,0.701 and 0.948,respectively.Before treatment,there was no significant difference in gender,age,mean arterial pressure and e GFR between the high FE IgG group(FE IgG>0.029)and low FEIgG group(FE IgG<0.029)(P>0.05).The remission time of high FEIgG group was(18.75±6.81)months,while it was(8.46±3.74)months in low FE IgG group,with significant difference(P<0.01).There was no difference in remission time of immunosuppressive therapy and supportive therapy in low FE IgG group(P=0.265),both of which were lower than the high-level immunosuppressive therapy group(P<0.001).The remission time of tacrolimus was shorter than that of cyclophosphamide in high FE gG group,but with no significant difference(P=0.131).There was significant difference in the remission time of tacrolimus between the high and low level groups of FEIgG(P<0.01).Under electron microscope,the ratio of foot process fusion and podocyte diffuse vacuolar degeneration in the high level group of FE IgG was higher than that in the low level group(P<0.01).Conclusions FEIgG can be used as a clinical indicator for predicting drug responsiveness and remission in patients with IMN,and is essential for early identification of high-risk patients and for making clinical decisions.Patients with high FE-IgG may benefit from early initiation of immunosuppressive therapy.