霉酚酸酯与环磷酰胺治疗Ⅳ型伴Ⅴ型狼疮性肾炎的疗效比较

Mycophenolate mofetil versus intravenous pulse cyclophosphamide for class Ⅳ plus Ⅴ lupus nephritis

目的:比较霉酚酸酯(MMF)与间断环磷酰胺(CTX)静脉冲击疗法治疗弥漫增生性狼疮性肾炎(Ⅳ)伴膜性病变型(Ⅴ型)狼疮性肾炎(Ⅳ+Ⅴ型LN)的临床疗效。方法:2000年1月至2004年1月间在解放军肾脏病研究所对经肾穿刺活检诊断为Ⅳ+Ⅴ型LN患者43例,比较同期激素联合MMF(MMF组,n=20),与激素联合CTX间断静脉冲击治疗(CTX组,n=23例)的疗效。MMF剂量1.5g/d或2g/d;CTX剂量为0.75～1g/m2·体表面积,每月静脉滴注一次。除MMF组血清肌酐高于CTX组外,其它基础病情两组相似。比较两组治疗6个月的完全缓解率、部分缓解率。结果:(1)临床缓解率:治疗6个月时MMF组缓解率高于CTX组:完全缓解率分别为20%和4.4%(P<0.05),部分缓解率分别为60%和34.8%(P<0.05)。(2)尿蛋白及尿红细胞变化:MMF组尿蛋白完全缓解率(≤0.4g/24h)高于CTX组(20%vs4.4%,P<0.05),红细胞缓解率也高于CTX组(63%vs50%,P>0.05)。(3)自身抗体变化:MMF与CTX组患者分别有78.9%及69.6%血清抗dsDNA转阴,ANA转阴率分别为36.9%和8.7%(P<0.05)。(4)肾脏病理变化:5例行重复肾活检。MMF组2例达部分缓解,肾小球增生性病变及血管炎性病变消失,上皮侧沉积物未减少,CTX组3例(1例部分缓解,2例无效)仍见增生性病变及袢坏死,2例未缓解者上皮侧沉积物增多。(5)副作用:MMF组并发带状疱疹2例,上呼吸道感染、白细胞减少各1例,CTX组2例并发带状疱疹及细菌性肺炎,4例有明显消化道症状,各有1例并发白细胞减少、肝酶升高和脱发。结论:激素联合MMF治疗Ⅳ+Ⅴ型狼疮性肾炎6个月的临床缓解率高于CTX,但绝大部分仅获部分缓解,对此类型LN最佳治疗方法仍需进一步临床研究。

Objective：Lupus nephritis with diffuse proliferation （ type Ⅳ lesion） and membranous lesion （type Ⅴ lesion） is associated with poor prognosis and refractory response to treatment. In this study, we retrospectively compared the clinical efficacy and side-effects in patients with class Ⅳ ＋ Ⅴ lupus nephritis who recieved mycophenolate mofetil （MMF） regime or intravenous pulse cyclophosphamide （CTX） regime. Methodology：Forty-three lupus patients classi- fied as type （ Ⅳ ＋ Ⅴ ） lupus nephritis after renal biopsy, according to the criteria of ISN/RPS 2003, were treated with intravenous methylprednisolone and MMF （ MMF group, n = 20） or with intravenous methylprednisolone and pulse cyclophophamide （CTX group,n =23）. MMF was given at a dosage of 1.5 ～2. 0 g/d, and CTX was administered as intravenous pulse therapy （0. 75 ～ 1 g/m2BSA） monthly for at least 6 months. Patients received these two regimes were comparable in general conditions and clinicopathological parameters for the activity and severity of renal damage. Patients in MMF group had a higher average level of serum creatinine. Results：In patients receiving intravenous CTX therapy, the corn-plete remission rate and the partial remission rate at the 6h month were only 4. 4% and 34. 8%. While in patients of MMF group, the complete remission rate and the partial remission rate at the 6th month were 20% and 60%, both with a signifi- cant statistic difference （ P 〈 0. 05 ）. MMF was found more effective in reducing proteinuria and retard the deterioration of renal function. Repeated biopsy data analysis revealed that vasculitic and proliferative lesions disappeared in MMF group. No significant change of membranous lesion was found in patients of both group. MMF was better tolerated with lower adverse reaction rate, such as pneumonia and upper gastrointestinal symptoms. No patient dropped out for side effect. Conclusion ：The combined therapy of MMF and steroid is more effective and tolerable than CTX pulse therapy in the induction treatment of patient with LN （ Ⅳ ＋ Ⅴ ）. MMF was more effective in improving renal vascuditic lesion. No significant ascendancy in controlling membranous lesion was found in MMF treated patients.