他克莫司治疗Ⅳ型和Ⅴ型狼疮性肾炎安全有效

摘要：环磷酰胺（CYC）治疗狼疮性肾炎（LN）疗效肯定，但可能导致某些严重副反应。他克莫司(TAC)可能作为LN的治疗选择。本项非随机开放标签研究纳入40例患弥漫性肾小球肾炎或膜性肾病的狼疮性肾炎患者，67.5%(27/40)的患者24小时尿蛋白定量＞3.5g，50%(20/40)的患者肾小球滤过率(eGFR)减低(<60mL /min/1.73m2)。本研究将患者分为两组，tac组20例，应用tac 0.04-0.08 mg/kg/d联合强的松12个月，cyc组20例，前6个月应用静脉cyc(750 mg/m2 月)联合强的松，后6个月应用硫唑嘌呤(aza) (100 mg/d)联合强的松，比较两组疗效及副反应。tac诱导治疗及缓解治疗的目标浓度分别为6-8 ng/ml及4-6 ng/ml，肾功能不全患者的目标浓度为4.0 ng/ml。tac组，经过两周治疗，尿蛋白由5.00 ± 1.91 g/d显著下降至2.54 ± 1.68 g/d(p < 0.001)，同期cyc组尿蛋白下降至4.9 ± 19.4 g/d，tac组与之相比差异具有显著性，p="0.001。TAC组65.0%(13/20)的患者在治疗1个月时达到部分缓解，而CYC组缓解率为0(0/20),P＜0.001。治疗5个月时TAC组完全缓解率显著高于CYC组(55.0%" vs.15.0%, p="0.008)，治疗12个月时有类似的结果(75.0%" vs.40.0%, p="0.025)。12个月时TAC组血清抗ds-DNA水平及SLEDAI评分改善较CYC组更为显著(P" ="0.031," p="0.003)。经过12个月治疗，TAC组肾小球滤过率由59.90" ± 23.64 ml/min/1.73m2的基线值改善为93.75 ± 28.52 ml/min/1.73m2(p="0.001)。CYC组中，2例病人进展至终末期肾病(ESRD)，3例患者发生重症肺炎，其中1例死亡。我们的初步研究提示TAC对于肾脏病变较重的狼疮性肾炎是一种安全、有效的治疗方法，与CYC序贯Aza疗法比较，其严重副反应发生率低。但仍需进一步大规模试验验证。

附原文：Treatment of lupus nephritis (LN) with cyclophosphamide (CYC) is effective but retains a certain severe adverse effect. Tacrolimus (TAC) may be a suitable treatment for LN. Forty patients with diffuse proliferative or membranous LN were recruited for this non-randomized open-label study - 67.5% (27/40) had nephrotic proteinuria (>3.5 g/day) and 50.0% (20/40) had low estimated glomerular filtration rate (eGFR) (<60 ml/min/1.73m(2)). we compared the efficacy and adverse effects of tac (0.04-0.08 mg/kg/d)/prednisone for 12 months (tac group, n="20)" with intravenous cyc (750 mg/m(2) per month)/prednisone for six months followed by azathioprine (aza) (100 mg/day)/prednisone for six months (cyc group, n="20)." the tac target concentration was 6-8 ng/ml or 4-6 ng/ml, respectively, when induction or maintenance therapy was required and 4.0 ng/ml for patient with renal insufficiency. in the tac group, mean urinary protein excretion decreased significantly from 5.00 ± 1.91 g/day at baseline to 2.54 ± 1.68 g/day after two weeks of therapy (p < 0.001), compared with the cyc group (4.9 ± 19.4 g/day), p="0.001," and 65.0% (13/20) achieved partial remission at one month, compared with the cyc group (0/20), p < 0.001. the incidence of complete remission (cr) was significantly higher in the tac group than in the cyc group (55.0% vs.15.0% by five months, p="0.008," and 75.0% vs.40.0% by 12 months, p="0.025," respectively). the significant improvement in serum anti-dsdna and systemic lupus erythematosus (sle) disease activity index (dai) was in the tac group relative to the cyc group at 12 months (p="0.031," p="0.003," respectively). the egfr improved in the tac group from 59.90 ± 23.64 ml/min/1.73m(2) at baseline to 93.75 ± 28.52 ml/min/1.73m(2) after 12 months, p="0.001." in the cyc group, two patients developed end-stage renal disease (esrd), three patients experienced serious pneumonia, and one patient died. our preliminary study showed tac is a safe and effective treatment for ln with severe renal disease, and with less-severe adverse events compared with cyc followed aza therapy. further larger sample studies are needed to confirm our conclusion.

引自：Wang S, Li X,et al. Tacrolimus versus cyclophosphamide as treatment for diffuse proliferative or membranous lupus nephritis: a non-randomized prospective cohort study. Lupus. 2012 May 8.