霉酚酸酯与间断环磷酰胺冲击疗法治疗Ⅳ型狼疮性肾炎疗效的比较

CLINICAL AND PATHOLOGICAL STUDY OF MYCOPHENOLATE MOFETIL(MMF)THERAPY VERSUS INTERMITTENT CYCLOPHOSPHAMIDE PULSE TREATMENT IN SEVERE DIFFUSE PROLIFERATIVE LUPUS NEPHRITIS(DPLN)

目的 :比较霉酚酸酯 (MMF)与间断环磷酰胺静脉冲击疗法 (CYC)治疗Ⅳ型狼疮性肾炎 (LN)的近期临床疗效及对肾脏病理改变的影响 ,探讨MMF治疗LN的适应证。 方法 :46例患者均经临床和肾活检确定为活动性Ⅳ型LN ,其中 2 3例经CYC治疗无效者采用激素联合MMF(1 0～ 1 5g/d)治疗 (MMF组 ) ,另 2 3例患者接受激素联合CYC治疗 (CYC组 ) ,两组患者病情相似 ,随访≥ 6个月。MMF组及CYC组中分别有 15例、12例在治疗 3～ 6个月时进行重复肾活检。 结果 :①临床疗效 :治疗 6个月时MMF组尿蛋白及尿RBC下降程度大于CYC组。尿蛋白及尿RBC减少超过基础值的 5 0 %者 ,MMF组分别占 6 9 6 %及 91 3% ,CYC组分别为 47 8%和6 5 2 %。尿蛋白转阴和血尿消失率MMF组分别为 34 8%、43 5 % ,CYC组则分别为 2 1 7%和 39 1%。MMF降低血清冷球蛋白血症、ANA及A dsDNA的作用强于CYC组。②肾脏病理改变 :重复肾活检显示MMF组肾组织急性指数 (AI)下降程度大于CYC组 ,MMF组AI由 16 4± 7 8降至 4 0± 2 0 ,CYC组由 12 3± 4 0降至 6 4±3 0。MMF组肾小球细胞浸润、免疫复合物沉积、血管袢坏死、袢内血栓均消失 ,细胞性或细胞纤维性新月体及间质活动性血管炎病变显著减少 ,而CYC组仍有较多患者遗留上述病变。③副反应

Preliminary studies have shown that MMF is effective in the treatment of refractory DPLN.In this study,the clinical efficacy and the influences on renal histological lesions between MMF and pulse cyclophosphamide (CYC) therapy in DPLN were compared. METHODOLOGY Forty six patients with active DPLN were treated by MMF or pulse CYC therapy.23 cases who were refractory to CYC therapy were given MMF at a dosage of 1 0～1 5 g/d and oral prednisone(MMF Group).Another 23 cases were given intravenous methylprednisolone(total dose 2 0～3 0g)initially and then oral prednisone,pulse therapy with CYC (0 75～1 0g/m 2 BSA) was given monthly for 6months and then quarterly (CYC Group).Patients in two groups were comparable in age,sex distribution and severity of renal damage.All patients were treated for more than 6 months.15 cases in MMF Group and 12 cases in CYC Group had repeated renal biopsy after the treatment for 3～6 months.The clinical efficacy and renal histological changes were compared between the two groups. RESULTS ①Clinical efficacy:MMF therapy was found to be more effective in reducing proteinuria and hematuria,with the decrement below the half of the baseline urinary protein excretion and urinary red blood cell count in 69 6% and 91 3% cases in MMF Group,while only 47 8% and 65 2% in CYC Group respectively.MMF was more effective in inhibiting of autoantibodies production (especially in anti dsDNA antibodies) and in decreasing serumcryoglobulin level. ②Repeated renal biopsy demonstrated that reduction of active index was more prominent in MMF group.More importantly,MMF treatment showed much stronger effects in reducing the glomerular cell infiltration and immune complex deposits,decreasing the proportion of glomerular necrosis and microthrombi,as well as crescents and lupus vasculitis. ③The incidence of gastrointestinal symptoms(26 1% and 43 5% in MMF and CYC group respectively)and infectious complications(17 4% and 30 4% in MMF and CYC Group respectively)was lower in MMF group. CONCLUSION MMF was more effective in controlling the activity of DPLN and renal vascular lesions than CYC pulse therapy with fewer complications.MMF can be a choice for the treatment of active DPLN,especially for those with renal vascular lesions.