多靶点治疗难治性肾小球疾病临床观察

Treatment of Refractory Glomerular Diseases in Patients with Multitarget Therapy

目的观察激素加霉酚酸酯（mycophenolate mofetil,MMF）和他克莫司（tacrolimus,FK506）的多靶点方案治疗难治性肾小球疾病的疗效及安全性。方法 2008年5月2010年3月收治的15例狼疮性肾炎（lupusnephritis,LN）、3例膜增生性肾小球肾炎（membranoproliferative glomerulonephritis,MPGN）及3例膜性肾病（membranous nephropathy,MN）患者,因多种免疫抑制剂治疗无效或复发而改用多靶点疗法。泼尼松以30~40 mg/d起始,逐渐减量。MMF和FK506起始剂量分别为0.5 g/d或1 mg/d,目标血药浓度分别为20~40 mg/（h.L）或5~8 ng/mL。定期随访观察肝肾功能、尿蛋白定量、不良反应等指标。结果治疗6个月时15例LN中7例（46.7%）完全缓解（complete remission,CR）,5例（33.3%）部分缓解（partial remission,PR）,3例（20%）无效（no response,NR）。3例MPGN均表现为NR。3例MN中2例（66.7%）PR,1例（33.3%）NR。治疗过程中呼吸道感染及脱发各1例,胃肠不适2例,肌酐逐步升高3例,无死亡或退出者。结论多靶点疗法对难治性LN安全、有效,可作为其他免疫抑制剂治疗无效或复发时的选择方案,但对MPGN和MN疗效欠佳,需进一步研究。

Objective To investigate the efficacy and safety of multitarget therapy with steroid,mycophenolate mofetil（MMF） and tacrolimus（FK506） in the treatment of refractory glomerular diseases.Methods Fifteen patients with lupus nephritis（LN）,3 patients with membranoproliferative glomerulonephritis（MPGN） and 3 patients with membranous nephropathy（MN） who failed the previous immunosuppressive therapy from May 2008 to March 2010 in our hospital were treated with multitarget therapy.The initial dose of prednisone was 30-40 mg/d and then tapered gradually.MMF and FK506 were started at 0.5 g/d or 1 mg/d,and the target blood concentration of the two drugs was 20-40 mg/（h·L） and 5-8 ng/mL respectively.Clinical parameters such as liver and renal function,urine protein,and side effects were recorded and analyzed in the regular follow-up.Results After 6 months of treatment,7（46.7%） of the 15 LN patients achieved complete remission（CR）,5（33.3%） achieved partial remission（PR）,while 3（20%） failed this treatment and had no response（NR）.All of the three MPGN patents had NR to this combined therapy.Two（66.7%） of the 3 MN patents achieved PR while 1（33.3%） had NR.No patient withdrew or died because of side effects.One patient developed upper respiratory infection,one experienced alopecia,two developed gastrointestinal syndrome and three experienced gradual increasing in the serum creatinine.Conclusion Multitarget therapy with FK506,MMF and steroid is an effective and safe therapy for refractory lupus nephritis and it can be used in patients who are resistant to the conventional immunosuppressive therapy.However,this combined therapy does not meet a satisfactory result in patients with MN and MPGN,which entails further study.