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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 observe the efficacy and safety of multi-target regimen of mycophenolate mofetil (MMF) and tacrolimus (FK506) in the treatment of refractory glomerular disease. Methods Fifteen patients with lupus nephritis (LN), 3 patients with membranoproliferative glomerulonephritis (MPGN) and 3 patients with membranous nephropathy (MN) were recruited in May 2008 and March 2010, respectively. , Because of a variety of immunosuppressive agents ineffective or relapse and use multi-target therapy. Prednisone with 30 ~ 40 mg / d starting, tapering. The starting doses of MMF and FK506 were 0.5 g / d or 1 mg / d, respectively, and the target plasma concentrations were 20-40 mg / (h.L) or 5-8 ng / mL, respectively. Regular follow-up observation of liver and kidney function, urinary protein, adverse reactions and other indicators. Results The complete remission (CR) was achieved in 7 cases (46.7%) in 5 LNs (6 cases), partial remission (PR) in 5 cases (20.3%) and no response , NR). 3 cases of MPGN showed NR. Two of three MNs (66.7%) had PR, and one (33.3%) had NR. In the course of treatment, 1 case of respiratory infection and hair loss, 2 cases of gastrointestinal discomfort, 3 cases of progressive increase in creatinine, no death or withdrawal. Conclusions Multi-target therapy is safe and effective for refractory LN and can be used as an alternative to other immunosuppressive agents in the treatment of relapse or failure. However, the curative effect of MPGN and MN is poor and needs further study.