吗替麦考酚酯联合糖皮质激素治疗激素抵抗特发性膜增殖性肾小球肾炎

Treatment of mycophenolate mofetil combined with prednisone for steroid-resistant idiopathic membranoproliferative glomerulonephritis

目的观察吗替麦考酚酯（MMF）联合糖皮质激素治疗激素抵抗特发性膜增殖性肾小球肾炎（IMPGN）的临床疗效。方法共13例患者，经肾穿刺活检诊断为MPGN，并排除继发性因素，明确诊断为IMPGN，其中4例中等量蛋白尿、9例大量蛋白尿、9例高血压、11例肾功能不全。在MMF治疗前，均经过足量糖皮质激素治疗（每日泼尼松1mg／kg）至少8周，尿蛋白均无明显下降。随后泼尼松在8周内减量至每日0．5mg／kg，同时加用MMF1．5g／d。结果13例患者在泼尼松治疗前尿蛋白量（24h）为（4．1±1．4）g；Scr为（131．0±44．9）μmol／L；MDRD公式估算肾小球滤过率（eGFR）（63．2±26．8）ml·min-1（1．73m2）-1。接受足量泼尼松治疗8周后，尿蛋白量（24h）为（4．2±1．5）g；Scr为（133．2_±52．8）tzmol／L；eGFR为（63．3±27．1）ml·min-1．（1．73m2）-1．差异均无统计学意义。加用MMF治疗3个月后，尿蛋白量（24h）轻微减少，为（3．8±1．2）g；Scr为（127．3±43．7）μmol／L；eGFR为（65．7±26．8）ml·min-1（1．73m2）-1，差异亦均无统计学意义。MMF治疗6个月后，尿蛋白量（24h）显著下降至（2．5±0．9）g（P〈0．05）；Scr为（109．5±31．0）μmol／L（P〈0．05）；eGFR为（72．9±25．3）ml·min-1（1．73m2）-1（P〈0．05）。MMF治疗12个月后，尿蛋白量（24h）为（1．5±0．6）g（P〈0．01），13例均达到部分缓解（尿蛋白量下降〉50％）；Scr为（95．9±22．5）μmol／L（P〈0．01）；eGFR为（81．2±23．8）ml·min-1．（1．73m2）-1（P〈0．01）。治疗过程中仅1例出现轻微的胃肠道症状。结论MMF联合糖皮质激素治疗激素抵抗IMPGN能明显减少蛋白尿，改善肾功能，无明显不良反应。

Objective To observe the efficacy of the treatment of mycophenolate mofetil （MMF） combined with prednisone on steroid -resistant idiopathic membranoproliferative glomerulonephritis （IMPGN） patients with moderate to severe proteinuria. Methods Thirteen cases were diagnosed as IMPGN by renal biopsy after excluding secondary factors. Among 13 patients, 9 had severe proteinuria and another 4 had moderate proteinuria, 9 with hypertension and 11 with decreased renal function. Before MMF therapy, all of the cases were resistant to the treatment of glucocortieoid （prednisone 1 mg· kg-1· d-1） for 8 weeks or more. The dose of MMF was 1.5 g/d. Patients were followed up every month for blood pressure, urinary protein excretion, liver and kidney function, complete blood count, and adverse effects. Results At the initiation, the 24 h urinary protein excretion was （4.1 ±1.4 ） g, Ser （131.0±44.9） μmol/L, and estimated glomerular filtration rate （eGFR） （63.3±26.8） ml·min-1 （1.73 m2）-1. After prednisone therapy for at least 2 months, the 24 h urinary protein excretion （4.2±1.5） g, Scr （133.2±52.8）μmol/L and eGFR （ 63.3 ±27.1 ） ml ,main-1 （ 1.73 m2）-1 did not change significantly. After 3 months of the addition of MMF, 24 h urinary protein excretion declined slightly [（3.8±1.2） g, P〉0.05], After 6 months, 24 h urinary protein excretion declined significantly [（2.5±0.9） g, P〈0.05], with decrease in Set and eGFR[（97.2±27.3） t.Lmol/L and （81.3_±24.2） ml.min-1 （1.73 m2）-1, P〈0.05）]. At the end of 1 year, 24 h urinary protein excretion was only （1.5±0.6） g（P〈0.01 ）, Ser and eGFR were （95.9 ±22.5） μmol/L and （81.2 ±23.8） ml.min-1（1.73 m2）-1 （P〈0.01）. All the patients experienced a partial remission of proteinuria （urinary protein excretion decreased by 50% or more）. Adverse event including stomach upset was found in 1 patient. Conclusion MMF combined with glucosteroids can effectively decrease proteinuria and improve renal function without obvious side effect in steroid-resistant IMPGN.