霉酚酸酯治疗难治性狼疮性肾炎疗效观察

目的 探讨霉酚酸酯(MMF)治疗难治性狼疮性肾炎(LN)的疗效，以及临床难治性的情况与T细胞亚群改变的关系。方法 LN患者分为两组：治疗组30例，经大剂量激素联合环磷酰胺间断静脉疗法无效或复发者；对照组29例，为随机抽取的同期住院患者，采用流式细胞仪检测两组T细胞亚群。结果 ①LN治疗组症状缓解20例(占66．7％)，部分缓解7例(占23．3％)，有效率占90％；26例伴镜下血尿者中，24例血尿消失；17例伴水肿者中，16例水肿消退；伴高血压14例，12例血压恢复正常，与对照组比较有效率均显著增高(P＜0．05)。②治疗组CD8较治疗前显著降低(P＜0．01)，CD^4 ／CD8^ 显著升高(P＜0．01)；对照组CD3、CD4、CD4^ ／CD8^ 及CD56均无明显差异。结论 MMF治疗难治性LN与经大剂量激素联合环磷酰胺间断静脉疗法相比疗效较好，尤其对控制LN活动期的缓解率高，且有调整T细胞亚群作用。     

霉酚酸酯治疗重症狼疮性肾炎疗效观察

狼疮性肾炎(LN)是继发性肾脏病导致终末期肾衰竭的最常见病因.根据中山大学附属第一医院肾内科肾穿刺病理活检资料,LN占继发性肾小球疾病的81%.其病理改变以细胞外基质的积聚、肾小球、肾小管、血管及间质的损害为特征.多年来,由于糖皮质激素及细胞毒药物的联合应用,其肾脏的生存率有了显著提高,但是长期应用大剂量环磷酰胺(CTX),毒副作用大,继发感染,使原发病加重,是死亡的重要原因.对于重症及难治性LN的治疗,如何在初始阶段的个体化治疗中,取得最大的疗效和最小的副作用,新型免疫抑制剂霉酚酸酯(MMF)对治疗难治性、重症LN疗效佳,副作用小,近期已被临床重视及选用.近年来我们应用霉酚酸酯(MMF)治疗LN患者36例,并与环磷酰胺(CTX)治疗的32例患者对照,现将结果报告如下.     

霉酚酸酯治疗难治性狼疮性肾炎的临床研究

目的 :观察霉酚酸酯 (MMF)治疗难治性狼疮性肾炎 (LN)的疗效、副作用及停药后复发情况。方法 :对糖皮质激素和环磷酰胺治疗无效或复发的 2 6例难治性LN患者 (其中 2 1例病理诊断为Ⅳ型 )改用MMF联合中、小剂量糖皮质激素治疗。MMF治疗量为 1.0～ 1.5 g/d ,维持治疗量为 0 .5g/d ,治疗时间 3～ 12个月 ,平均 (7.4 9± 2 .84 )个月 ,11例治疗达 12个月后停药观察 6～ 2 0个月 ,平均 (13.2 3± 6 .32 )个月。结果 :经MMF治疗后 ,14例肾衰竭中有11例血清肌酐恢复正常 ,需透析的 3例也完全脱离透析。 76 .9%患者尿蛋白减少半量以上 ,34.6 %患者尿蛋白转阴 ,6 9.2 %患者血尿消失 ,84 .6 %患者血清抗ds-DNA转阴 ,92 .3%患者血清ANA转阴。未见明显的药物副作用。 11例停药后病情稳定 ,未再发狼疮活动。结论 :MMF对传统免疫抑制剂和糖皮质激素无效或复发的难治性LN ,尤其是Ⅳ型LN有独特的疗效 ,副作用小 ,停药后近期不复发     

来氟米特与霉酚酸酯治疗狼疮肾炎患者的临床疗效比较

目的探讨来氟米特与霉酚酸酯治疗狼疮肾炎的临床疗效和安全性。方法选择我科40例狼疮肾炎患者随机分为2组,即来氟米特组（A组）和霉酚酸酯组（B组）,每组20例。2组均联合泼尼松治疗。对比观察2组治疗前和治疗后第3、6个月的系统性红斑狼疮疾病活动性指数（sys—temic lupus erythematosus disease activity index,SLEDAI）评分、24h尿蛋白定量、血白蛋白、血红蛋白、肾小球过滤率（eGFR）、补体C3、抗双链DNA抗体（ds-DNA）、血沉水平的变化及临床疗效,并分别记录不良反应。结果与治疗前相比,来氟米特组和霉酚酸酯组血白蛋白、血红蛋白均明显升高,24h尿蛋白定量明显降低,滤过率水平明显上升,血沉水平及ds—DNA水平明显下降,补体c3水平明显升高,能够改善肾功能及免疫指标,且2组间差异无统计学意义（P〉0．05）。来氟米特组恶心呕吐、肝功能损害、白细胞数降低、皮疹、腹泻、月经不调、高血压、感染等不良反应发生率分别为15％（3例）、20％（4例）、10％（2例）、10％（2例）、5％（1例）、15％（3例）,5％（1例）,5％（1例）;霉酚酸酯组恶心呕吐、肝功能损害、白细胞数降低、皮疹、腹泻、月经不调、高血压、感染等不良反应发生率分别为10％（占2例）、5％（1例）、0例、5％（占1例）、5％（占1例）、0例、0例、5％（占1例）。结论来氟米特和霉酚酸酯均能有效控制狼疮肾炎,但霉酚酸酯不良反应相对较轻。     

霉酚酸酯治疗狼疮性肾炎进展

霉酚酸酯是一种选择性作用于淋巴细胞的新型免疫抑制剂 ,本文综述了其药理作用及其在狼疮性肾炎动物模型及患者中的应用进展。     

霉酚酸酯对弥漫增生型狼疮性肾炎患者的疗效观察

目的 :比较霉酚酸酯 (MMF)和环磷酰胺 (CTX)冲击疗法治疗Ⅳ型狼疮性肾炎的疗效及不良反应。方法 :A组 2 0例 ,间断性CTX冲击疗法联合激素 1mg·kg-1·d-1治疗 ;B组 2 0例 ,MMF联合激素治疗。随访 12个月。结果 :CTX组、MMF组治疗LN均能降低蛋白尿、血尿 ,改善肾功能和免疫指标 ,两组无统计学意义 (P >0 .0 5 ) ,但MMF组治疗效果优于CTX组。不良反应 ,MMF组明显低于CTX组 (P <0 .0 5 )。结论 :CTX、MMF都能有效地控制狼疮性肾炎 ,且MMF具有一定的优越性     

霉酚酸酯治疗狼疮性肾炎进展

霉酚酸酯是一种选择性作用于淋巴细胞的新型免疫抑制剂，本文综述了其药理作用及其在狼疮性肾炎动物模型及患者中的应用进展。     

霉酚酸酯对狼疮性肾炎的治疗效果及肾脏病理分析

目的研究探讨霉酚酸酯(MMF)对狼疮性肾炎(LN)的临床治疗效果。方法收集2008年1月至2017年12月于本院治疗的40例LN患者,应用数字随机表法将其随机分为两组,每组20例。对照组采用环磷酰胺治疗,观察组采用霉酚酸酯治疗,比较两组的临床疗效、不良反应、治疗前后的疾病活动度指数、肾功能指标及肾脏病理指标。结果两组的总有效率比较差异无统计学意义(P>0.05),观察组的总有效率高于对照组(P<0.05)。治疗前,两组的疾病活动度指数、血肌酐(Scr)、尿素氮(BUN)、24 h尿蛋白、纤维新月体、白金耳和微血栓差异均无统计学意义(P>0.05),治疗后,与对照组比,观察组的疾病活动度指数、BUN、Scr、24 h尿蛋白和总不良反应发生率均明显降低(P<0.05)。两组患者的纤维新月体、白金耳和微血栓均明显降低,但组间比较差异无统计学意义(P>0.05)。结论霉酚酸酯治疗狼疮性肾炎可以达到与环磷酰胺相当的临床疗效,霉酚酸酯相比于环磷酰胺可以减少患者不良反应,其安全性更加安全可靠。     

霉酚酸酯治疗狼疮性肾炎(WHO Ⅳ)探讨

过去 ,霉酚酸酯 (ＭＭＦ)多用于肾移植中 ,最近有个案报告用ＭＭＦ治疗狼疮性肾炎 (ＷＨＯⅣ ) 〔1〕,但ＭＭＦ治疗狼疮性肾炎 (ＬＮ)的确切疗效 ,尚无定论 ,我们选择了 2 0例用环磷酰胺 (ＣＴＸ)治疗无效 ,治疗后复发或不能用ＣＴＸ(因白细胞减少 )的ＬＮ(ＷＨＯⅣ )患者 ,改用ＭＭＦ治疗 ,并进行治疗前后自身对照 ,以探索其疗效并观察其不良反应。资料与方法1　诊断标准与研究对象　所选 2 0例病人均符合美国风湿病学会 1982年修订的ＳＬＥ分类诊断标准 4条以上 ,全部作过肾活检 ,均为Ⅳ型狼疮性肾炎 ,所有ＬＮ都有活动性 ,所选病人大多曾…     

Maintenance therapy with mycophenolate mofetil for children with severe lupus nephritis after low-dose intravenous cyclophosphamide regimen

Although recent studies on adults with lupus nephritis indicate that mycophenolate mofetil (MMF) may be effective in maintaining remission for patients who previously received short-term intravenous cyclophosphamide (IVCY) induction therapy, the experience with the new immunosuppressive agent in children with severe lupus nephritis has not been as satisfactory thus far. To assess the efficacy and safety of maintenance therapy with MMF, we prospectively analyzed four patients with biopsy-proven severe lupus nephritis (three girls, one boy; mean age 12 years; two with class IIIA, two with class IVG(A); mean duration of lupus nephritis 7 months) receiving MMF for at least 6 months after induction treatment. These patients had been treated previously with 6 months of low-dose IVCY combined with oral mizoribine and steroids for induction, followed by therapy with MMF adjusted to maintain predose mycophenolic acid (C0-MPA) levels at 2-5 mcg/ml. Mean follow-up after staring MMF was 27.5 months (range 6-41). The mean MMF dose required was 405 +/- 49 mg/m(2) per 12 h, which maintained mean C0-MPA levels of 3.3 +/- 0.41 mcg/ml. No patient experienced renal flares during maintenance therapy with MMF, which permitted a significant reduction in mean prednisolone dose from 11.9 +/- 1.3 to 3.9 +/- 2.6 mg/day (P = 0.003). No significant gastrointestinal or hematologic side effects of MMF were noted. This preliminary study demonstrates that maintenance therapy with MMF after a low-dose IVCY regimen appears to be a promising intervention without adverse effects in children with severe lupus nephritis. These data should be confirmed by a prospective randomized multicenter clinical trial.     

The effect of mycophenolate mofetil on primary and secondary treatment of primary glomerulonephritis and lupus nephritis

Background  Mycophenolate mofetil (MMF) has shown to be a reliable choice in the treatment of glomerulonephritis. We retrospectively reviewed the clinical course and response to MMF therapy in 49 patients with primary glomerulopathy (37 patients) and lupus nephritis [class III (five patients) and IV (seven patients)]. Methods  Patients were treated with MMF for more than 6 months as a primary (18 patients) or an adjunctive treatment (31 patients). Patients were also on methylprednisolone (2–20 mg/day) and angiotensin converting enzyme inhibitor/angiotensin receptor blocker. Results  The mean age of the patient cohort was 33.69 ± 12.4 years (range 19–59 years). Twenty-four-hour urinary protein excretion was reduced from 3.50 ± 3.08 g prior to the commencement of MMF drug therapy to 1.21 ± 1.44 and 0.99 ± 1.34 g at the sixth and 12th months of MMF therapy, respectively (P < 0.05 for all). During this same period, significant increases in serum total protein (from 5.92 ± 1.38 to 6.59 ± 0.79 and 6.81 ± 0.77 g/dl) and albumin levels (from 3.23 ± 1.10 to 3.93 ± 0.67 and 4.21 ± 0.50 g/dl) were detected, whereas total cholesterol and low-density lipoprotein levels were found to be significantly decreased (P < 0.05 for all). Serum creatinine levels did not significantly change. The efficacy of MMF in reducing proteinuria was similar in both first line and an adjunctive therapy. The efficacy of MMF therapy began at the third month of treatment and continued through to the 12th month. Conclusion  Mycophenolate mofetil therapy was found to be useful in achieving improvements in proteinuria and nephrotic syndrome and stabilizing renal function. It was also a well-tolerated drug by the majority of the patients. Based on our results, we suggest that MMF may be alternative therapy for resistant/relapsing primary glomerulopathies and lupus nephritis.     

Randomized controlled trial of pulse intravenous cyclophosphamide versus mycophenolate mofetil in the induction therapy of proliferative lupus nephritis

Background: The aim of the present study was to evaluate the efficacy of mycophenolate mofetil in the induction therapy of proliferative lupus nephritis. Methods: Forty‐four patients from eight centres with newly diagnosed lupus nephritis World Health Organization class III or IV were randomly assigned to either mycophenolate mofetil (MMF) 2 g/day for 6 months or intravenous cyclophosphamide (IVC) 0.75–1 g/m² monthly for 6 months in addition to corticosteroids. Results: Remission occurred in 13 out of 25 patients (52%) in the IVC group and 11 out of 19 patients (58%) in the MMF group (P = 0.70). There were 12% in the IVC group and 26% in the MMF group that achieved complete remission (P = 0.22). Improvements in haemoglobin, the erythrocyte sedimentation rate, serum albumin, serum complement, proteinuria, urinary activity, renal function and the Systemic Lupus Erythematosus Disease Activity Index score were similar in both groups. Twenty‐four follow‐up renal biopsies at the end of therapy showed a significant reduction in the activity score in both groups. The chronicity index increased in both groups but was only significant in the IVC group. Adverse events were similar. Major infections occurred in three patients in each group. There was no difference in gastrointestinal side‐effects. Conclusions: MMF in combination with corticosteroids is an effective induction therapy for moderately severe proliferative lupus nephritis.     

A comparative study of two intensified pulse cyclophosphamide remission-inducing regimens for diffuse proliferative lupus nephritis: an Egyptian experience

Introduction  Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the short-term efficacy and toxicity of a course of low-dose remission-inducing IV CYC followed by azathioprine (AZA) in a prospective controlled study among Egyptian patients with severe LN. Patients and methods  In this single center, prospective clinical trial, we assigned 46 SLE patients with diffuse proliferative glomerulonephritis to either a high-dose (a maximum of 1 g/dose) of IV CYC (HD-CYC) for six monthly pulses followed by two quarterly pulses or a fixed low-dose (500 mg/dose) of IV CYC (LD-CYC) for six fortnightly pulses with a cumulative dose of 3 g. Each regimen was followed by AZA. The objective  To compare between efficacy, potential toxicity and outcome of parenteral LD-CYC versus HD-CYC therapy for severe LN. Results  Twenty patients (2 male and 18 female) received fortnightly fixed LD-CYC while 26 (5 male and 21 female) received monthly HD-CYC therapy. At the end of the study (1 year after starting therapy), there was no difference either in patients’ or in renal survival in both groups. Significant improvement of disease activity (SLE disease activity index) as well as rise of serum albumin was noticed with both regimens. Renal relapse was observed in 11.5% of HD-CYC patients and in none of the LD-CYC therapy patients. Treatment failure was seen in 5% and 3.4% (P = NS) of LD-CYC and HD-CYC patients, respectively. Infection (pneumonia and cellulitis) occurred in five patients in the LD-CYC group and four patients of HD-CYC; again this difference was not statistically significant. Conclusion  A remission-inducing regimen of LD-CYC (cumulative dose 3 g) followed by AZA for SLE patients with proliferative LN achieves clinical results comparable to those obtained with HD-CYC without serious infection in both regimens.     

Effects of mycophenolate mofetil and glucocorticoid on Henoch-Schonlein purpura nephritis in children

Objective To explore the effect and safety of mycophenolate mofetil (MMF) and glucocorticoid on Henoch-Schonlein purpura nephritis in children and compared with cyclophosphamide (CTX). Methods The data of 48 patients diagnosed as Henoch-Schonlein purpura by renal biopsy were retrospectively analyzed. Median follow-up time was 22(7, 48) months. The subjects were divided into 2 groups. 34 cases were in the MMF group: MMF (15-20 mg?kg-1?d-1 or 800-1200 mg/m2)+ prednisone, and 14 cases in the CTX group: CTX (8 - 12 mg?kg-1?d-1)+prednisone. Clinical and laboratory data were collected at baseline and 1, 3, 6 months after treatment. During follow - up, cumulative retreatment rate and adverse reactions after treatment were recorded. Results In two groups after treatment for 1, 3, 6 months, 24 hours urinary protein quantitative was significantly lower than the baseline value, serum albumin (sAlb) was significantly higher than the baseline value, and serum creatinine (Scr) indicated no statistically significant difference during the follow-up period. After the treatment of 1 month, the efficient rate of MMF group was higher than the CTX group (MMF 73.5 % vs 42.9%, P=0.046), the effective treatment of 3, 6 months at the end of the follow-up, no statistically significant difference were observed in the accumulative remission rate. The total rate of retreatment was 10.4% (5/48), where MMF group was lower that of the than CTX group (3.0% vs 28.6%, P＜ 0.001). The retreatment often occurred after discontinuation of prednisone and CTX, MMF reduction process. Eleven children received IMPDH2 gene polymorphisms test in MMF group, 9 AA children had shorter time for drugs to be effective than that of the AG and GG children. The incidence of adverse reactions of MMF group was obviously lower than CTX group at the end of the follow-up (8.8% vs 35.7%, P=0.025), where two groups developed fungal infection. Conclusions The short-term effect of both groups are the same, but the recurrent rate and incidence of adverse reactions of MMF group are lower than those of the CTX group. The preliminary study shows that IMPDH2 gene polymorphisms is associated with MMF curative effect and adverse reactions.     

不同剂量环磷酰胺治疗弥漫增殖性狼疮肾炎的疗效分析

目的 探讨不同剂量环磷酰胺（CTX）对弥漫增殖性狼疮肾炎各亚型的疗效差异。 方法 回顾性分析133例肾活检确诊的,接受糖皮质激素+CTX规律治疗的Ⅳ型（Ⅳ-G和Ⅳ-S亚型）或Ⅳ+Ⅴ型狼疮肾炎患者的基线Scr、尿蛋白量（24 h）、CTX剂量方案及预后情况。对各型各剂量组的预后情况进行比较。 结果 患者6个月内CTX平均累积剂量为（11.1±4.1） g。以6 g和12 g为界,将6个月时的CTX累积剂量分为高（>12 g）、中（>6~12 g）、低（≤6 g）3个剂量组。与低剂量组比较,高剂量组Ⅳ+Ⅴ型、活动或慢性（A/C）患者完全缓解率有改善的趋势（Ⅳ+Ⅴ型：67%比40%,P = 0.314;A/C：43%比0%,P = 0.212）,但未能明显改善Ⅳ-S和Ⅳ-G亚型的完全缓解率（Ⅳ-S亚型：67%比50%,P = 0.548;Ⅳ-G亚型：65% 比70%,P = 0.560）。高剂量组总不良反应高于低剂量组,但差异无统计学意义（51%比37%,P=0.224）。 结论 激素+高剂量CTX的治疗方案可提高Ⅳ+Ⅴ型及慢性病变患者的缓解率。     

Effects of mycophenolate mofetil for patients with crescentic lupus nephritis

Objective: To compare the effects, relapse ratio and outcomes between mycophenolate mofetil (MMF) and pulse intravenous cyclophosphamide (CTX) for the induction therapy in patients with crescentic lupus nephritis. Methodology: This is a retrospective, controlled study. Twenty-seven MMF therapeutic and twenty-five CTX therapeutic lupus patients with ≥50% crescent formation were enrolled in this study. The general conditions, clinicopathological findings, remission and relapse ratio, and outcomes of them were compared. Results: There was no significant difference of general condition and clinicopathological findings between MMF and CTX group. At 12 months, the total remission ratio in MMF and CTX group were 73.1% and 69.6%, while the complete remission ratio in MMF group (53.8%) was significantly higher than that in CTX group (26.1%). The relapse ratio in MMF group (10.5%) was significantly lower than in CTX group (43.8%). Forty per cent of PR patients in CTX group suffered from relapse. Until June 2005, the patients in CTX group received a follow time with 38.5 ± 21.2 (range 10∼80) months, and in MMF group the follow time was 41.1 ± 27.0 (range 12∼90) months. Two patients in MMF group and two in CTX group entered into end stage renal failure. The side effect of infection was more significant in CTX group. Conclusion: Higher complete remission ratio and lower relapse ratio were observed in MMF group than in CTX group. The side effect of infection was more infrequent in MMF group, which showed preferable security of MMF.