来氟米特与霉酚酸酯治疗表现为肾病综合征的过敏紫癜性肾炎的疗效比较

目的：比较来氟米特（LEF）与霉酚酸酯（MMF）治疗临床表现为肾病综合征的过敏紫癜性肾炎（HSPN）的临床疗效。方法：36例临床表现为肾病综合征的HSPN患者,分别采用激素联合LEF治疗（LEF组,n=18）,或采用激素联合MMF治疗（MMF组,n=18）。LEF或MMF正规使用6个月以上。收集治疗前及治疗6个月以后的血尿常规、尿红细胞计数、24h尿蛋白定量、肝肾功能、白蛋白及血脂等指标,同时记录不良反应。结果：（1）两组接受治疗后,尿蛋白和尿红细胞计数均明显减少（P〈0.01）,血白蛋白明显上升（P〈0.01）。（2）临床缓解率：LEF组总有效率为83.3%,MMF组总有效率为88.8%,两组之间无统计学差异;其中完全缓解率分别为50.0%和44.4%,部分缓解率分别为33.3%和44.4%,均无统计学差异（P〉0.05）。（3）两组患者均耐受良好,无明显副作用。结论：LEF和MMF联合激素治疗表现为肾病综合征的HSPN的临床缓解率相似,不良反应轻微。     

吗替麦考酚酯联合小剂量激素治疗膜性肾病的疗效观察

目的：观察吗替麦考酚酯（MMF）联合小剂量激素治疗特发性膜性肾病（IMN）的疗效及安全性。方法：选用60例肾穿刺确诊为MN肾病,并排除继发性肾脏病的患者,随机分为两组,治疗组采用MMF联合小剂量的泼尼松治疗,对照组采用间断静脉环磷酰胺（CTX）冲击联合泼尼松治疗;动态观察患者治疗前、治疗后6个月和12个月时24h尿蛋白定量、血清白蛋白（Alb）、谷草转氨酶（ALT）、血肌酐（Scr）的变化情况及不良反应发生情况。结果：经过6个月和12个月的治疗,治疗组总有效率分别为56.67%和70%;对照组总有效率分别为36.67%和43.33%。12个月治疗后,治疗组疗效明显高于对照组（P〈0.05）。结论：MMF联合小剂量激素可有效地治疗IMN,降低蛋白尿,稳定肾功能,且不良反应轻微。     

霉酚酸酯对难治性肾病综合征和弥漫增殖性狼疮肾炎的疗效比较

目的 :观察霉酚酸酯 (MMF)在治疗原发性难治性肾病综合征与弥漫增殖性狼疮性肾炎的疗效比较。方法 :观察难治性肾病综合征 15例及同期弥漫增殖性狼疮性肾炎 (ⅣLN) 18例。以强的松 0 .4mg～ 0 .7mg·kg-1·d-1联合MMF1.0～ 1.5 2次 /d ,3～ 6个月后减半维持 1年 ,定期随访。结果 :以强的松联合MMF治疗 ,对ⅣLN疗效良好 ,完全缓解率达 10 0 % ,其中 3个月内缓解 12例 ,6个月内缓解 17例。而在原发性肾病综合征中 ,对MCD和MsPGN疗效良好 ,与ⅣLN相似 ,在MN中 2例完全缓解 ,3例仅部分缓解 ,2例无效。而后者均在 6～ 9个月间 ,对FSGS和MPGN仅 1例在 9个月后部分缓解 ,2例无效。结论 :MMF对MCD和MsPGN效果良好 ,对MN显示部分疗效 ,对FSGS和MPGN的疗效较差。总体上MMF对难治性肾病综合征的疗效逊于ⅣLN。     

弥漫增殖性狼疮性肾炎的治疗及疗效分析

目的：分析比较霉酚酸酯（MMF）与环磷酰胺（CTX）治疗弥漫增殖性狼疮性肾炎的疗效。方法：回顾性分析118例膜增殖性狼疮性肾炎的治疗效果。MMF组56例,CTX组62例,两组均采用静脉甲基泼尼松龙500 mg×3次冲击后口服泼尼松治疗,MMF组给予MMF500 mg,2次/日,口服至少6月,CTX组给予静脉CTX冲击治疗,0.75~1.0 g/M2 BSA,每月1次×3次,之后3个月1次×2次,6个月1次×2次,总量〈8 g。结果：治疗3个月时,MMF组总有效率显著高于CTX组（42.9%VS 20.9%,P〈0.05）,且尿蛋白减少作用优于CTX组（-1.62±1.33 VS-1.04±0.68,P〈0.05）。治疗6个月,两组总有效率差异无统计学意义,但MMF组减少尿蛋白作用优于CTX组（-2.11±0.93 VS-1.64±1.23,P〈0.05）。治疗12个月时两组总有效率差异无统计学意义。副作用比较两组发生胃肠道反应、肝酶升高、白细胞减少差异无统计学意义,但CTX组发生感染及女性闭经较MMF组多（58.1%VS 41.1%,P〈0.05;21%VS 3.5%,P〈0.05）,而MMF组出现精神焦虑者明显增加（39.3%VS 12.9%,P〈0.05）。结论：MMF和CTX治疗弥漫增殖性狼疮性肾炎均有较好效果,但MMF作用更迅速,感染及闭经的副作用小。     

环孢素A与环磷酰胺对难治性肾病综合征疗效分析比较

目的：探讨环孢素A（CsA）与环磷酰胺（CTX）对难治性肾病综合征（RNS）的疗效比较。方法：2005年3月～2009年8月难治性肾病综合征患者纳入研究,随机分为两组,使用CsA治疗的患者作为CsA治疗组,使用CTX治疗的患者作为CTX治疗组。CsA组起始剂量1.0～1.5mg/kg,血药浓度调整在100～150ng/L。CTX组1.0g/次,1次/月,累积量不超过8g。观察两组蛋白尿、血浆白蛋白、肾功能变化情况及不良副作用。结果：（1）CsA组缓解率为59.2%（42/71）,其中23.9%（17/71）完全缓解;CTX组缓解率为50%（28/56）,其中19.6%（11/56）达完全缓解。两组资料比较差异无统计学意义（χ2=4.417,P〉0.05）。（2）MN型肾病患者,本研究中CsA组总缓解率78.6%（33/42）,完全缓解率为45.2%（19/42）;CTX组总缓解率为48.5%（16/33）,完全缓解率为21.2%（7/33）。两组比较差异具有统计学意义（χ2=8.280,P〈0.05）。（3）毒副作用：CsA组血压升高9例,6例Scr上升,肝功异常4例,高尿酸血症3例,肺部感染2例,占32.4%（23/71）;CTX组6例肝功能异常,4例白细胞减少,7例出现消化道不适症状（4例合并肝功能异常）,1例血尿,总共占32.1%（18/56）。结论：CsA与CTX对RNS患者的疗效总体无明显差别,但对MN,CsA疗效可能优于CTX,但维持时间及维持剂量仍需进一步研究。     

普乐可复联合激素治疗难治性肾病综合征临床观察

难治性肾病综合征一般是指激素依赖型和激素抵抗型的肾病综合征,约占原发性肾病综合征的39．9％～53．8％,既往传统治疗方案多给予激素联合细胞毒药物,如环磷酰胺（CTX）、环孢素（CsA）等治疗,但仍有部分无效,普乐可复作为新型钙调神经磷酸酶抑制剂,因其作用强,不良反应少,越来越广泛应用于自身免疫性疾病及器官移植术后。我科应用普乐可复联合激素治疗6例难治性肾病综合征患者,有明显疗效,报道如下。     

吗替麦考酚酯联合皮质类固醇治疗IgA肾病的疗效

吗替麦考酚酯（mycophenolate mofbtil，MMF）治疗狼疮性。肾炎及难治性肾病综合征疗效显著。笔者应用MMF联合激素治疗IgA肾病，报道如下。     

来氟米特对儿童难治性肾病综合征临床观察

目的：观察来氟米特对儿童难治性肾病综合征治疗效果。方法：对27例儿童难治性肾病综合征分为激素抵抗型9例,激素依赖型14例,频复发型4例,分别给予来氟米特1mg/kg,每日1次口服,连续3d后改为0.2～0.4mg/kg,每日1次,泼尼松2mg·kg-1.d-1,逐渐减至适当剂量维持或停用。结果：治疗前和治疗6个月后血白蛋白（P=0.0002）和24h尿蛋白（P〈0.0001）明显改善,27例儿童难治性肾病综合征治疗后部分缓解7例（25.93%）,完全缓解12例（44.44%）,总缓解率70.37%。在微小病变和非微小病变之间,差异具有统计学意义（P〈0.05）。结论：来氟米特对改善儿童难治性肾病综合征具有一定效果。     

环孢素A治疗儿童难治性肾病综合征26例疗效分析

目的探讨环孢素A治疗儿童难治性肾病综合征的临床疗效。方法 26例难治性肾病综合征患儿入院后口服环孢素A,剂量为2～4mg（/kg·d）,同时联合激素治疗,疗程3个月。治疗前及治疗后检测24h尿蛋白定量、血浆白蛋白、血浆胆固醇、尿素氮、血肌酐等指标。结果 26例患儿经治疗后,完全缓解14例,占53.85%;部分缓解10例,占38.46%;未缓解2例,占7.69%。结论环孢素A联合激素能有效治疗难治性肾病综合征。     

冯志荣主任医师治疗难治性肾病综合征经验

难治性肾病综合征是指原发性肾病综合征具备下列任何一项者：（1）肾病综合征患者按正规激素治疗缓解后半年内复发2次或1年内复发3次以上;（2）经激素治疗获得缓解,但在激素撤减过程中或停用激素后14d内复发者;（3）规范化激素治疗无效的肾病综合征[1]。是目前临床治疗最为棘手、预后较差的肾病。其中以膜性肾病为代表。     

环孢霉素A与环磷酰胺联合激素治疗膜性肾病的疗效比较

目的：比较环孢霉素A（CSA）与环磷酰胺（CTX）联合激素治疗成年人特发性膜性肾病（IMN）的疗效和安全性。方法：76例原发性肾病综合征患者经肾活检确诊为IMN,在诊断上排除了继发性膜性肾病,单用激素治疗无效或复发,随机分两组分别予CSA联用糖皮质激素治疗（CSA组）或CTX联用糖皮质激素治疗（CTX组）,疗程至少12个月。观察各组的24h尿蛋白定量、血浆白蛋白、肾功能、血糖、白细胞总数及其不良反应,以及治疗前后的完全缓解率、部分缓解率。全部患者且在正式进入研究治疗前未用或已停用类固醇激素和细胞毒药物达半年以上。结果：治疗3个月末,CsA组的24h尿蛋白、胆固醇、三酰甘油显著低于CTX组（P均〈0.01）,血清白蛋白显著高于CTX组（P〈0.01）。两组患者的血肌酐比较差异无统计学意义（P〉0.05）,而CTX组的WBC显著低于CsA组（P〈0.01）。CsA组完全缓解率显著高于CTX组（χ2=4.6317,P〈0.05）。治疗12个月末两组的完全缓解率差异无统计学意义（χ2=1.2575,P〉0.05）。CsA组的不良反应发生率（8/40=20.0%）显著低于CTX组（15/36=41.7%）（χ2=4.2146,P〈0.05）。结论：与CTX相比,CsA联用糖皮质激素对IMN治疗12个月的总体疗效相当,但CsA起效更快,近期疗效更好,不良反应更小。CsA≤5mg.kg-1.d-1用于肾功能正常IMN患者是安全有效的。     

Mycophenolate mofetil versus cyclophosphamide for inducing remission of ANCA vasculitis with moderate renal involvement.

OBJECTIVE: We performed a single-centre non-blinded clinical trial to compare the clinical efficacies of mycophenolate mofetil (MMF) and intermittent cyclophosphamide (CTX) pulse therapy as induction treatments in patients with antineutrophil cytoplasmic antibody (ANCA) vasculitis (AAV) and moderate renal involvement. METHODS: Patients with active AAV and serum creatinine <500 micromol/L received either MMF treatment (MMF group) or monthly CTX pulse therapy (CTX group) for 6 months. Disease activity was assessed using the Birmingham Vasculitis Activity Score (BVAS). The disease activity, remission rate, renal function and adverse reactions were compared between the two groups. RESULTS: A total of 35 patients (15 male, 20 female: aged 49.1 +/- 12.2 years) were enrolled, with 18 in the MMF group and 17 in the CTX group. Of the 35 patients, 28 were MPO-ANCA positive and 2 were PR3-ANCA positive. Four patients were lost to follow-up in the CTX group. At Month 6, BVAS scores were much lower in the MMF group than in the CTX group (0.2 +/- 0.89 versus 2.6 +/- 1.7, P < 0.05). In the intent-to-treatment analysis, 14 of 18 patients (77.8%) treated with MMF and 8 of 17 patients receiving CTX (47.1%) had complete remission with an absolute difference of 30.7%. Eight of 18 patients (44.4%) in the MMF group and 2 of 17 patients (15.4%) in the CTX group recovered renal function. Serum ANCA decreased to normal in 41.7% of patients in the MMF group and in 16.7% in the CTX group. Side effects in the MMF group were pneumonia (1), herpes zoster (1) and gastrointestinal symptoms (2), and in the CTX group were leukocytopenia (1), gastrointestinal distress (4) and pneumonia (1). CONCLUSION: Our study suggests that MMF effectively ameliorates disease activity and considerably improves renal function in patients with AAV. Further large-scale multicentre prospective randomized controlled trials will be needed to confirm these findings.     

激素联合来氟米特或环磷酰胺治疗慢性进展性IgA肾病的比较

目的：比较激素联合环磷酰胺（CTX）或来氟米特 （LEF）治疗慢性进展性IgA肾病（IgAN）的疗效及安全性.方法：回顾性分析2009年6月~2012年7月在我院确诊为IgAN患者,Lee氏分级Ⅱ级或以上,并应用激素分别联合CTX或LEF治疗的患者57例,CTX组25例,LEF组32例;收集患者治疗前及每月随访资料.结果：经治疗IgAN尿蛋白总缓解率达87.7%,治疗期间CTX组和LEF组尿蛋白部分缓解分别为7例（28.0%）和11例（34.4%）,P=0.607;CTX组和LEF组尿蛋白完全缓解分别为14例（56.0%）和18例（56.2%）,P=0.985.CTX组和LEF组部分缓解时间分别为（2.95±1.70）月和 （3.27±3.01）月,差异有统计学意义（P=0.048）,CTX组和LEF组尿蛋白完全缓解时间分别为（5.45±3.31）月和（6.69±5.82）月,P=0.052.随访中CTX组副反应发生率12.0%,LEF组副反应发生率6.25%.结论：激素联合CTX或LEF治疗慢性进展性IgAN均有相同的疗效,CTX组部分缓解时间较LEF快,长期疗效及安全性有待进一步观察.     

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.     

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.     

环孢素A与吗替麦考酚酯治疗难治性肾病综合征疗效对比

目的：通过检测临床指标的变化,观察对比环孢素A和吗替麦考酚酯治疗难治性肾病综合征的疗效差异。方法：将本院自2008年1月以来收治的56例原发性难治性肾病综合征患者随机分为CsA、MMF两组,在口服泼尼松0.5mg.kg-1.d-1治疗的基础上,CsA组口服环孢素4mg·kg-1.d-1,MMF组口服吗替麦考酚酯0.75mg2/d,进行1年的随访,在治疗前、治疗3、6、12个月分别记录尿常规、24h尿蛋白定量、肝功能（AST、ALT、Alb）、肾功能（CRE,UA,GLU）、血脂以及环孢素血药浓度等指标的变化,并记录不良反应。结果：从治疗1个月开始,部分患者的尿蛋白定量减轻,血浆白蛋白水平开始有所恢复,前后结果差异有统计学意义（P〈0.05）,两组患者之间差异无统计学意义（P〉0.05）。结论：环孢素A、吗替麦考酚酯均可以有效的治疗难治性肾病综合征,治疗同期两者差异不明显。     

Combination of immunosuppressive agents in treatment of steroid-resistant minimal change disease and primary focal segmental glomerulosclerosis

BACKGROUND: Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most prevalent histopathological lesions in idiopathic nephrotic syndrome (INS). The latter is associated with high morbidity and mortality due to symptomatic anasarca, bacterial infections, venous and arterial thromboembolism, and potential progression to end-stage renal disease in the case of FSGS. Traditionally, most patients are treated with corticosteroids, cyclophosphamide (CTX) or calcineurin-inhibitors (C-I). Unfortunately, many patients become steroid or C-I dependent, with the inherent risk of long-term side effects, or are resistant to both. The aim of this paper is to report on our experience with a new protocol of a combination of immunosuppressive agents added sequentially to improve the response of steroid and C-I refractory or resistant-INS and to minimize the long-term side-effects of single-agent treatment. METHODS: Twenty-one patients with corticosteroid-resistant and C-I refractory INS (6 with MCD and 15 with FSGS) were treated prospectively over 6 and a half years. Our protocol consisted of an initial regimen of C-I followed by the addition of mycophenolate mofetil (MMF) and then by monthly intravenous CTX for 3 consecutive months. Dose reduction of C-I or/and MMF was attempted afterwards at 4-months intervals. Patients who remained refractory to the previously mentioned protocol were treated with an additional course of pulse Solu-Medrol given for 3 days followed by oral corticosteroids tapered over 6 months in addition to a second course of intravenous CTX given for 3 consecutive months. RESULTS: With the initial regimen, two patients with MCD, remained in complete remission (CR) without any therapy after the course of CTX. Fifteen patients had variable response to C-I and MMF, but they achieved CR after CTX and their initial dosage of C-I and MMF were reduced to nearly one half. The remaining four patients had refractory form of FSGS even after the initial regimen, yet responded with CR to the additional course of steroid/CTX. However, no success with dose-reduction, in C-I and MMF, was achieved in the latter four patients. CONCLUSION: Our study represents the first clinical trial with prospective and adequate follow-up of combination therapy of immunosuppressive agents in INS. This method is effective and safe for treatment of patients who are refractory to the conventional single-agent therapy.     

大剂量长春新碱冲击治疗成人难治性肾病综合征疗效观察

目的观察钱桐荪教授设计的大剂量长春新碱（VCR）冲击疗法在成人难治性原发性肾病综合征中的疗效和不良反应。方法选择成人难治性原发性肾病综合征患者13例,采用VCR4mg加入0．9％氯化钠注射液或5％葡萄糖注射液100ml中静脉注射,每个月1次,共治疗6个月。结果13例患者中,完全缓解及基本缓解11例,部分缓解2例;总有效率为100％。起效时间为0．5～1个月。治疗前、后肝功能均在正常范围,治疗前1例血肌酐155umol／L,治疗后降至正常。最多见不良反应者为10例有不同程度的肢体末端麻木和轻度脱发;消化道症状明显6例,其中较严重1例。首次治疗不良反应较重,然后逐渐减轻。结论VCR冲击治疗成人难治性肾病综合征疗效好,患者均能耐受不良反应。值得进一步研究和探讨。     

Combination of Immunosuppressive Agents in Treatment of Steroid-Resistant Minimal Change Disease and Primary Focal Segmental Glomerulosclerosis

Background. Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most prevalent histopathological lesions in idiopathic nephrotic syndrome (INS). The latter is associated with high morbidity and mortality due to symptomatic anasarca, bacterial infections, venous and arterial thromboembolism, and potential progression to end-stage renal disease in the case of FSGS. Traditionally, most patients are treated with corticosteroids, cyclophosphamide (CTX) or calcineurin-inhibitors (C-I). Unfortunately, many patients become steroid or C-I dependent, with the inherent risk of long-term side effects, or are resistant to both. The aim of this paper is to report on our experience with a new protocol of a combination of immunosuppressive agents added sequentially to improve the response of steroid and C-I refractory or resistant-INS and to minimize the long-term side-effects of single-agent treatment. Methods. Twenty-one patients with corticosteroid-resistant and C-I refractory INS (6 with MCD and 15 with FSGS) were treated prospectively over 6 and a half years. Our protocol consisted of an initial regimen of C-I followed by the addition of mycophenolate mofetil (MMF) and then by monthly intravenous CTX for 3 consecutive months. Dose reduction of C-I or/and MMF was attempted afterwards at 4-months intervals. Patients who remained refractory to the previously mentioned protocol were treated with an additional course of pulse Solu-Medrol given for 3 days followed by oral corticosteroids tapered over 6 months in addition to a second course of intravenous CTX given for 3 consecutive months. Results. With the initial regimen, two patients with MCD, remained in complete remission (CR) without any therapy after the course of CTX. Fifteen patients had variable response to C-I and MMF, but they achieved CR after CTX and their initial dosage of C-I and MMF were reduced to nearly one half. The remaining four patients had refractory form of FSGS even after the initial regimen, yet responded with CR to the additional course of steroid/CTX. However, no success with dose-reduction, in C-I and MMF, was achieved in the latter four patients. Conclusion. Our study represents the first clinical trial with prospective and adequate follow-up of combination therapy of immunosuppressive agents in INS. This method is effective and safe for treatment of patients who are refractory to the conventional single-agent therapy.