双重血浆置换联合激素治疗重症狼疮性肾炎的临床观察

Combination therapy of double filtration plasmapheresis and glucocorticoid in severe lupus nephritis

目的：观察双重血浆置换（DFPP）联合激素治疗在重症狼疮性肾炎（LN）治疗中的作用及安全性。 方法：31例活动期重症LN患者（女19例，男12例），年龄24.4？10.9岁（11～54岁），系统性红斑狼疮疾病活动指数（SLE-DAI） 16.0±3.5分， 血清肌酐（SCr） 3.4±2.1mg/dl， 22例表现为急进性肾炎综合征，其中11例需行肾脏替代治疗。所有患者均接受肾活检，病理类型分别为Ⅳ型（19例）、Ⅲ型（1例）、Ⅳ＋Ⅴ型（8例）、Ⅴ＋Ⅲ型（2例）和Ⅴ型（1例）。DFPP采用EC50W作为一级血浆分离器，血浆成分分离器EC20W作为二级滤器，每次处理血浆量为2倍血浆容量。所有患者同时给予甲基泼尼松龙静脉治疗（0.5g/d×3～6d），后续采用激素联合吗替麦考酚酯、他克莫司或间断环磷酰胺冲击治疗，观察DFPP治疗前后SLE-DAI、免疫学指标和肾功能的变化，随访疗效及不良反应。 结果：（1）临床疗效：DFPP平均治疗2.6土0.7次（1～3次），治疗结束时，SLE-DAI（16.0？3.5 vs 9.7？1.5，P〈0.01）和SCr（3.4？2.1 mg/dl vs 2.8？1.9mg/dl，P〈0.05）均显著下降。11例透析患者中6例摆脱透析，5例患者肾功能无改善，转为维持性肾脏替代治疗；DFPP治疗后，镜下血尿明显减少，4例患者肉眼血尿消失，尿蛋白定量无明显变化；（2）免疫学指标变化：DFPP治疗后，血清IgG显著下降（10.9？5.2 vs 4.6？2.0g/L，P〈0.01）；ANA滴度及dsDNA滴度下降， 43%（13/30）患者dsDNA转阴；补体C3和C4无明显改变，DFPP治疗后血CD4＋淋巴细胞无明显改变明显下降[（287.3土183.4）个/ul vs （322.3±257.5）个/ul，P〉0.05]； （3）随访结果：平均随访10.1？6.4月（1~29月），在末次随访观察时，6例患者获得CR，18例获得PR， 6例进入维持性透析；（4）不良反应 DFPP治疗过程中1例患者出现导管感染，1例患者出现低血压反应。 结论：DFPP能迅速有效清除自身抗体，降低狼疮活动，改善肾功能，是重症LN治疗的一种有效的辅助手段。DFPP治疗LN的适应症、疗程和剂量尚需深入探讨。

Objective： To investigate the clinical efficacy and safety of double filtration plasmapheresis （DFPP） accompanied with corticosteroid in patients with severe lupus nephritis （LN）. Methodology： Thirty one patients （19 females and 12 males, average age of 24.4？10.9 y） with severe LN including class Ⅳ （n=19）、Ⅲ（n=1）、Ⅴ＋Ⅳ（n=8）、Ⅴ＋Ⅲl（n=2） and Ⅴ（n=1） were enrolled in this study. Among them, 22 cases showed rapidly progressive glomerulonephritis（RPGN） with elevated serum creatinine（SCr）（300.6？185.6？mol/L）, and 11 of them needed renal replacement therapy. DFPP was performed with two-fold plasma volume on each session using membrane type plasma component separator （EC50W and EC20W,Asahi Kasei Kuraray,Japan）. Results： （1） Clinical efficacy： After DFPP treating 2.6 times（1～3）for each patient, their SLE-DAI was reduced significantly from （16.0？3.5） to （9.7？1.5） （P〈0.01）and SCr was decreased from （300.6？185.6）？？mol/L to （247.5？168.0） ？mol/L （P〈0.05）. Six patients got off dialysis respectively. Gross hematuria disappeared in 4 patients and there was no change in proteinuria. （2）Immunologic parameters： After DFPP,the levels of serum IgG were decreased from （10.9？5.2） g/L to （4.6？2.0） g/L （P〈0.01）, and the titers of anti-dsDNA antibody were significantly declined, while the levels of complements and lymphcytes had no change. （3）Follow up： 31 patients were followed up for 1～29 months（10.1？6.4）. 6 patients achieved complete remission, 18 had partial remission and 6 developed to ESRD with maintenance hemodialysis. （4）Adverse effect： one had catheter infection and one had hypotension episodes during DFPP treatment. Conclusion： DFPP could decrease activity of SLE and improve renal function through rapidly and effectively clearance of antibodies in severe LN. So DFPP accompanied with corticosteroid is an effective therapeutic method for severe LN. However, the right indication, suitable course and dosage of DFPP will need to deeply investigate.