吗替麦考酚酯治疗弥漫增生性狼疮性肾炎的多中心临床研究

目的　多中心、前瞻性观察吗替麦考酚酯 (MMF)治疗弥漫增生性狼疮性肾炎的临床疗效和不良反应。方法　全国 9家医院共收集系统性红斑狼疮患者 75例 (男 1 3例 ,女 62例 ) ,均经肾活检确定为活动性弥漫增生性狼疮性肾炎 (LN IV) ,年龄 (31 0± 1 0 1 )岁 ,病程 (38 9± 52 5)个月 ;其中经正规激素联合环磷酰胺治疗无效者 2 6例 ,复发者 2 1例 ,初治患者 2 8例。治疗方案采用激素联合MMF。MMF起始剂量为 0 5～ 2 0g/d ,随访时间≥ 6个月。 38例治疗后行重复肾活检 ,并进行急性指数 (AI)、慢性指数 (CI)、免疫球蛋白 (Ig)及补体沉积半定量评分。结果　MMF平均起始剂量 (1 2 6±0 30 )g/d ,治疗 3、6个月时MMF平均剂量分别为 (1 2 1± 0 30 )g/d、(0 95± 0 33)g/d。治疗 3个月狼疮活动分数 (SLE DAI)由 1 6 9± 6 7降为 8 1± 4 8(P <0 0 1 ) ,血红蛋白由 (92± 2 1 )g/L升至 (1 1 2± 2 8)g/L(P <0 0 5) ,尿蛋白由 (4 2 4± 2 66)g/d降至 (2 1 8± 3 75)g/d(P <0 0 5) ,血清白蛋白升至 (35 3±6 9)g/L(P <0 0 1 ) ,肾功能明显改善 ,无活动性尿沉渣 ;治疗 6个月尿蛋白继续下降至 (1 54± 1 60 )g/d ,血红蛋白、血清白蛋白继续升高。血清A dsDNA抗体阳性及低补体血症患者比例显著降低。

Mycophenolate mofetil treatment for diffuse proliferative lupus nephritis: a multicenter clinical trial in China

OBJECTIVE: To investigate the efficacy and side effects of mycophenolate mofetil (MMF) in the treatment of diffuse proliferative lupus nephritis( DPLN). METHODS: 75 patients [13 male,62 female; age (31.0 +/- 10.1)y] with biopsy-proven active DPLN from nine hospitals in China from Jan. 1999 to Jan. 2000 were enrolled in this study, of whom 26 patients were refractory to conventional treatment of steroids and cyclophosphamide. 21 patients presented with relapses and 28 patients were newly diagnosed. All the patients were treated with a combined regimen of MMF and steroids. Patients who had severe active renal lesions were initially given intravenous methylprednisolone followed by oral prednisone. The initial dosage of MMF was 0.5 approximately 2.0 g/d and the administrati on maintained at least 6 months. 38 patients had repeat renal biopsy after treatment. SLE disease activity (SLE-DAI) score, renal active index (AI),chronic index(CI) and density of immunoglobulins, complement deposition was assessed before and after MMF treatment. RESULTS: The mean starting dosage of MMF was (1.26 +/- 0.30) g/d, it was reduced to (1.21 +/- 0.30) g/d and (0.95 +/- 0.33) g/d at the end of the 3(rd) and 6(th) month respectively. The post-treatment Hb level increased from (92 +/- 21) g/L to (112 +/- 28) g/L(3 mo) and (116 +/- 21) g/L(6 mo), while proteinuria decreased from (4.24 +/- 2.66) g/d to (2.18 +/- 3.75) g/d (3 mos, P < 0.05) and (1.54 +/- 1.60) g/d( 6 mos,P < 0.01). Renal function impairment present in some of the patients also showed marked improvement. The proportion of patients with positive A-dsDNA antibody and hypocomplementemia was significantly reduced after 6 months of MMF treatment. SLE-DAI score in this group of patients decreased from (16.9 +/- 6.7) to (8.1 +/- 4.8) (P < 0.01) by the end of 3 months. Repeat renal biopsy in 38 patients 3 approximately 6 months after the treatment showed a significant decrement of AI ( 13.30 +/- 5.51) vs (3.38 +/- 1.98),P < 0.01, and an increment of CI (1.62 +/- 1.48) vs (2.62 +/- 1.85), P > 0.05. Immunoglobulins and complement deposition scores decreased from (9.39 +/- 3.51) to(6.71 +/- 3.16 ),P < 0.05. During the study period, 12 episodes of infection (16.0%) were recorded including pneumonia(2.7%), herpes zoster(8.0 %), urinary tract infection(2.7%), and tuberculosis(2.7%). Other side effects included gastrointestinal symptoms (10.7%), hirsutism(6.7%), leukocytopenia (1.3%) and transient elevation of SGPT(2.7%). CONCLUSION: MMF in a dosage of 0.5 approximately 2.0 g/d combined with steroids is effective to control the lupus activity of DPLN and well tolerated by the patients.