霉酚酸酯治疗35例Ⅳ型狼疮性肾炎的长期随访

目的回顾性总结霉酚酸酯(MMF)治疗Ⅳ型狼疮性肾炎(LN)的临床疗效,探讨MMF的剂量,了解复发情况.方法35例活动性LN患者(其中10例为初治,25例已经使用大剂量激素或联合间断环磷酰胺静脉冲击疗法),采用MMF联合激素治疗6个月以上.所有患者治疗前尿蛋白＞2.0g/24h,有明显血尿或管型尿,肾活检显示活动性Ⅳ型LN.MMF起始剂量1.0～1.5g/d,初治患者同时给予足量激素诱导治疗,对已经使用大剂量激素者继续口服中、小剂量强的松.疗效标准分为缓解、部分缓解及无效.在患者病情明显好转后MMF逐步减至0.5～0.75g/d维持.结果①MMF治疗时间6～36个月(平均12.7±6.8月).在治疗期间共有27例(占77.1%)获得缓解(尿蛋白＜1.0g/d,无活动性尿沉渣、肾功能稳定、血清A-dsDNA阴性,无肾外活动),6例获部分缓解,2例无效.获得缓解的时间为3～15个月(平均6.5±4.7月).随着MMF治疗时间延长,缓解率逐步增高MMF治疗3、6、12、24个月的缓解率分别为25.7%、60%、72.7%及83.3%.18例患者减量或停药前行重复肾活检,肾组织活动性指数显著下降.②30例患者在治疗3～6个月,临床获得缓解或部分缓解后开始减量.在MMF维持治疗3～9个月间12.5%患者复发,7例患者停用MMF3～9个月后3例复发.③治疗过程中各有2例患者并发肺炎及疱疹病毒感染,未见肝功能异常及白细胞减少.结论MMF1.0～1.5g/d剂量联合激素治疗能有效控制狼疮性肾炎活动,诱导治疗时间应6个月以上.在获得缓解或部分缓解后MMF可逐步减量,但维持剂量不宜太小.停止MMF治疗后复发率高,因此必须有替代药物治疗以降低MMF停药后的高复发率.     

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

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 :MMF组胃肠道     

他克莫司延缓移植性肾病进展的临床观察

目的:观察他克莫司(FK506)与霉酚酸酯(MMF)联合应用延缓移植性肾病肾功能进展的疗效。方法:选择肾移植术后肾功能异常,并经移植肾活检病理证实为慢性移植性肾病患者46例,将原环孢素A(CsA)切换为FK506,同时联合MMF和激素。FK506起始剂量0·08mg/(kg·d),MMF1.5g/d,监测切换12个月后血清肌酐、肾小球滤过率(GFR)[ml/(min·1·73m2)]、24h尿蛋白定量(g)变化。结果:切换为FK506治疗12个月后,平均血清肌酐由(293±45)μmol/L降至(198±24)μmol/L(P<0·05)。GFR由(39·77±2·35)ml/(min·1·73m2)提高至(49·87±3·17)ml/(min·1·73m2),24h尿蛋白定量由(4·8±0·8)g降至(1·9±0·7)g(P<0·05)。副作用包括高血糖(6例)、震颤(8例)、腹泻(4例)、白细胞减少(2例)、带状疱疹(1例)、骨痛(1例)。结论:FK506可以有效延缓移植肾病进展。     

他克莫司与环孢素A对肾移植患者霉酚酸酯血药浓度影响的比较

目的:观察肾移植患者他克莫司(FK506)联用霉酚酸酯(MMF)方案和环孢素A(CsA)联用MMF方案术后6月血浆霉酚酸(MPA)浓度的变化,对比两组之间MPA浓度和MMF剂量的差别。方法:51例首次肾移植患者根据免疫抑制方案分为FK506组(n=20)和CsA组(n=31),两组MMF使用方法相同。采用高效液相色谱法测定MPA浓度,用MPA药物曲线下面积(MPAAUC0~12)反映MPA浓度,测定移植术后15天、30天、3月和6月MPAAUC0~12。结果:与CsA组相比,FK506组MPAAUC0~12在15天和1月时较高[15天:(56·0±21·1)vs(33·2±8·9)mg/L·h;1月:[(54·0±12·5)vs(38·5±12·9)mg/L·h,P=0·01],而MMF剂量无明显差别;3月和6月时两组之间MPAAUC0~12无差别,但FK506组MMF剂量较CsA组低[3月:(1·10±0·29)g/dvs(1·27±0·25)g/d,P<0·05,6月:(1·02±0·18)g/dvs(1·22±0·10)g/d,P<0·05]。两组在4个时间点上体重,血红蛋白、血清肌酐和白蛋白水平均无差别。结论:FK506与CsA相比,联用同样剂量的MMF在术后1月内其MPA浓度较高,而术后3月起可减低MMF剂量而达到同样的MPA浓度,提示在临床实践中要注意MMF剂量个体化。     

普乐可复与环磷酰胺诱导治疗Ⅳ型狼疮性肾炎的疗效比较

目的:比较观察口服普乐可复(FK506)与环磷酰胺静脉冲击(IVC)联合激素诱导治疗Ⅳ型狼疮性肾炎(LN)的疗效及安全性,探讨FK506合适的治疗剂量与血药浓度范围。方法:经肾活检诊断为Ⅳ-G型(2003年ISN/RPS分类)活动性、女性LN患者34例,平均年龄(27·1±9·9)岁,尿蛋白定量≥2·0g/d,血清白蛋白<3·0g/dl,随机分为FK506组[n=17,起始剂量0·1mg/(k·/d)]和IVC组(n=17,0·5~1·0g/m2BSA,1/月×6月),同时口服泼尼松(0·6mg/kg·d),其中22例患者接受甲基泼尼松龙静脉冲击治疗。主要评价指标为治疗6个月完全缓解率(CR,定义为尿蛋白定量<0·4g/24h,尿红细胞正常范围,无管型尿及白细胞尿,血清白蛋白≥3·5g/dl,SCr正常或上升不超过正常范围15%,无肾外狼疮活动),次要观察指标为治疗6个月部分缓解(PR)率和有效率(CR+PR)。结果:(1)临床疗效:治疗6个月FK506组和IVC组的有效率分别为94·1%和82·4%,FK506组有11例患者获得CR(11/17,64·7%),高于IVC组(7/17,41·2%)(P=0·303);FK506组出现PR的时间明显短于IVC组[(1·9±1·2)月vs(3·2±1·8)月,P=0·034],而两组获得CR的时间分别为(4·0±1·3)月和(5·0±1·2)月;两组患者SLE-DAI、尿蛋白水平、血尿、血清白蛋白、补体C3、C4水平及A-dsDNA阳性率较治疗前均有显著改善;(2)FK506的剂量和浓度:FK506的剂量平均为0·08~0·09mg/(kg·d),血药浓度为5·7~7·1ng/ml;获得CR的患者血药浓度平均为(8·1±3·9)ng/ml,PR的患者为(5·2±2·7)ng/ml,其中3例血药浓度低于5ng/ml的患者亦获得CR;(3)不良反应:FK506组肝酶升高、感染等发生率低于IVC组,未见白细胞减少、月经紊乱,而短暂SCr升高、高血压、高血糖、脱发等并发症高于IVC组,但无统计学差异。结论:FK506是诱导治疗Ⅳ型LN的一种有效的免疫抑制剂,起效快,不良反应较小。     

吗替麦考酚酯治疗系统性红斑狼疮的多中心前瞻性研究

目的　观察吗替麦考酚酯 (骁悉 )治疗系统性红斑狼疮的疗效及安全性。方法　通过观察治疗前后狼疮病情活动指数 (SLEDAI)、2 4h尿蛋白定量等指标的变化 ,对比分析骁悉与环磷酰胺的疗效和安全性。结果　 6 8例SLE患者完成为期 6个月的研究 ,骁悉组 36例 ,环磷酰胺 (CTX)组 32例。骁悉组SLEDAI由治疗前的 2 0± 8减少至治疗后 4± 3(P <0 0 1) ,CTX组由 2 1± 6减少至 7± 8(P <0 0 1) ,治疗后两组对比实验组改善较对照组明显 (P <0 0 1)。尿蛋白的变化 :骁悉组由 (3 2±2 8)g降至 (1 1± 1 1)g (P <0 0 1) ,环磷酰胺组由 (2 6± 2 4 )g降至 (1 3± 1 4 )g (P <0 0 1) ,治疗后两组对比差异无显著性 (P >0 0 5 )。总有效率骁悉组为 97 2 % (35 / 36 ) ,环磷酰胺组为 93 8% (30 / 32 )(P >0 0 5 )。骁悉组的副作用发生率为 2 2 2 % (8/ 36 ) ,环磷酰胺组为 6 9 7% (2 3/ 33) (P <0 0 5 )。结论　骁悉作为一种免疫抑制剂治疗SLE和环磷酰胺一样有效 ,并且安全性更高 ,对于CTX无效的患者亦有效。     

缬沙坦和尼群地平对原发性高血压患者血清可溶性粘附分子影响的对比研究

目的　对比研究缬沙坦和尼群地平对原发性高血压 (EH )患者血压及血清可溶性粘附分子sICAM 1,sVCAM 1水平的影响。方法　随机对照方法设计 ,将 6 4例轻中度原发性高血压患者分为两组 ,分别予缬沙坦 (80mg/d)和尼群地平 (10～ 30mg/d)治疗 6周 ,治疗前后抽血 ,用酶联免疫方法 (ELISA)测定外周血清中可溶性粘附分子sICAM 1,sVCAM 1水平。另选择 2 5例健康人作为对照组。结果　治疗前与对照组比较 ,高血压患者血清中可溶性粘附分子sICAM 1,sVCAM 1水平升高 ,分别为 [(318 2± 2 7 5 ) μg/Lvs (2 71 5± 2 6 8) μg/L ,P <0 0 5 ]和 [(5 90 6± 4 0 1) μg/Lvs (4 17 9± 38 7) μg/L ,P <0 0 1]。治疗后两组的血压均明显下降 (P <0 0 5 ) ,两组间无差异。缬沙坦组可溶性粘附分子sICAM 1,sVCAM 1水平均较治疗前明显下降 ,分别为[(32 0 5± 2 3 6 ) μg/Lvs (2 80 2± 2 5 4 ) μg/L ,P <0 0 5 ]和[(5 86 2± 4 2 5 ) μg/Lvs (4 5 1 2± 38 9) μg/L ,P <0 0 1]。而尼群地平组可溶性粘附分子sICAM 1,sVCAM 1水平较治疗前无明显下降 (P >0 0 5 )。结论　与尼群地平比较 ,缬沙坦不仅能有效降低血压 ,还能抑制血管壁的炎症反应 ,有利于预防和延缓动脉粥样硬化的发生和发展。     

索他洛尔治疗阵发性心房颤动的前瞻性多中心临床研究

目的　研究索他洛尔对控制国人阵发性心房颤动的疗效、合适剂量和安全性。方法　 2 0个医疗中心入选 2 40例阵发性心房颤动患者用索他洛尔治疗 ,剂量从 80 m g/ d开始 ,根据具体情况 ,适量渐增 ,最大剂量不超过 2 40 mg/ d。观察临床疗效及心电图、动态心电图指标。结果　完成疗程观察者共 2 1 2例 ,男性 1 2 6例 ,女性 86例 ,平均年龄 (5 6 .2± 9.6 )岁。服药时间平均 (1 0 .5 9± 4.6 3)周。治疗后 3周的有效率 :80 m g/ d者 (2 1 2例 )为 5 7% ;1 6 0 m g/ d者 (91例 )为 81 .3% ;2 40 m g/ d者 (2 4例 )为 87.5 %。发生副作用者共 9例 (4.4% ) ,包括心动过缓 5例 ,头晕 1例 ,左束支阻滞 1例 ,乏力 2例。服药后 6周 ,心率平均下降 1 4 % ,有 6例因心率 <6 0次 / min而停药。对血压影响较小 ,但有 2例因收缩压降至 90mm Hg (1 m m Hg=0 .1 33k Pa)而停药。服药后校正 QT间期从 (0 .389± 0 .0 2 0 ) s增加至 (0 .42 1±0 .0 30 ) s(P<0 .0 5 ) ,但 QT间期离散度从 (73.5 3± 4.0 0 ) s降至 (5 3.90± 37.5 0 ) s(P<0 .0 1 )。结论　本研究结果显示索他洛尔是一种控制阵发性心房颤动的有效药物 ,副作用小 ,安全性较好 ,剂量推荐为 80～1 6 0 m g/ d,亦可用至 2 40 mg/ d,疗效发生于 1～ 3周内 ,持续用     

高原地区老年慢性肺心病重度急性加重期患者糖皮质激素的应用

目的　探讨高原老年慢性肺心病因呼吸道感染致重度急性加重期患者应用肾上腺糖皮质激素 3d和 10d对减轻气道阻塞、改善气体交换和症状的效果。　方法　 78例患者随机分为 2组 ,Ⅰ组 (3 9例 )仅前 3d静脉滴注地塞米松 0 2mg/kg ,1次 / 12h ,随后 7d改用生理盐水 ,Ⅱ组 (3 9例 )前 3d静脉滴注地塞米松 0 2mg/kg ,1次 / 12h ,随后 3d为0 1mg/kg ,1次 / 12h ,最后 4d为0 1mg/kg,1次 /d。治疗期间 2组患者均口服相同剂量的舒喘灵、氨茶碱、必嗽平和西咪替丁 10d ,选用敏感抗生素。治疗前、治疗 3d、10d后分别测定肺功能、动脉血气 ,并观察呼吸困难、咳嗽、咳痰的变化。　结果　治疗 3d ,Ⅰ组 1s用力呼气容积占预计值百分比 (FEV1% )、动脉血氧分压 (PaO2 )、动脉血二氧化碳分压 (PaCO2 )分别为 (3 5 9± 7 6) %、(44 4± 5 8)mmHg、(46 1± 5 8)mmHg ,Ⅱ组分别为 (3 4 8± 7 3 ) %、(45 0± 5 7)mmHg、(46 9± 5 0 )mmHg ;治疗 10d后 ,Ⅰ组 3项指标分别为(3 6 7± 7 6) %、(45 6± 6 1)mmHg、(44 8± 5 2 )mmHg ,Ⅱ组分别为 (42 0± 7 1) %、(49 7± 6 3 )mmHg、(41 7± 4 2 )mmHg ,与治疗前比较均为P <0 0 1。治疗 3d时 ,两组患者的症状评分、FEV1%、FEV1/用力肺活量 (FVC)比值、PaO2 、PaC     

霉酚酸酯分散片治疗狼疮性肾炎的疗效及安全性

目的：前瞻性非对照观察激素联合霉酚酸酯（MMF）分散片诱导治疗Ⅲ型及Ⅳ型狼疮性肾炎（LN）的疗效及不良反应。方法：经肾活检确诊为活动性Ⅲ型及Ⅳ型LN患者采用激素联合MMF分散片（赛可平）诱导治疗。所有患者均先接受甲基泼尼松龙静脉冲击（0．5g／d&#215;3d）治疗，继以口服泼尼松0．8mg（kg&#183;d），4周后泼尼松逐渐减量。MMF起始剂量0．75～1．5g／d，根据霉酚酸（MPA）AUC0-12h调整MMF剂量，MPA AUC0-12h目标值为30～40mg&#183;h／L，观察治疗6个月的疗效和不良反应。疗效主要指标为完全缓解率（定义为尿蛋白定量〈0．4g／d，无活动性尿沉渣，血白蛋白i〉35g／L，SCr正常）和部分缓解率（定义为尿蛋白和尿沉渣红细胞计数下降超过基础值的50％，血白蛋白〉／30g／L，SCr稳定）。结果：共23例患者[女性19例，男性4例，平均年龄（32．5&#177;10．9）岁]进入本研究，其中病理类型Ⅲ型9例，Ⅳ型14例，20例为初治患者。MMF平均治疗剂量（1．13&#177;0．40）g／d，相应MPA浓度（35．80&#177;9．31）mg&#183;h／L。诱导治疗6个月时11例（47．8％）完全缓解，11例（47．8％）部分缓解，总缓解率95．6％，其中Ⅲ型完全缓解率（55．6％vs42．9％，P〉0．05）和总缓解率（100％vs92．9％，P〉0．05）高于Ⅳ型。不良反应包括带状疱疹3例（13．0％）、胃肠道症状1例（4．3％）及肝酶升高1例（4．3％），无一例并发肺部感染。结论：激素联合MMF分散片（赛可平）诱导治疗III及IV型LN有较高缓解率，无严重不良反应。监测MPA血药浓度有助于调整MMF剂量。     

肾移植术后抗排斥药FK506的临床应用

目的研究FK506预防肾移植术后排斥反应的效果和安全性。方法肾移植患者22例,其中18例为始用组,4例为切换组。FK506起始用0.2me／(kg·d),以后逐步减量,3个月后维持血浓度于3～12μg/L水平。切换组于停用CsA24h后应用FK506,剂量和血浓度与始用组相同。同时合并应用MMF0.5g,每日3次口服,以及术后前10天大剂量甲基强的松龙静滴,第11天改强的松口服并减量,6个月后维持强的松15mg／d。所有病例均严密观察并行血尿等生化分析。结果始用组移植肾功能好,平均血肌酐水平l02μmol／L,无一例出现排斥反应。切换组中2例异常的肝功能好转;肾功能进行性减退的2例切换后,血肌酐相对稳定。有血糖升高4例和高血压5例,用药后能控制,其他副反应有上呼吸道和下尿路感染、胸痛、恶心、呕吐、腹泻、腹部不适等。结论FK506是肾移植术后有确切疗效的基础抗排斥药,与MMF、皮质醇合用能有效地预防急性排斥的发生,并可控制慢性排斥的进展。应用剂量适当,无明显的肝、肾毒副作用,但有血糖升高及高血压副作用,药物可以控制。其它呼吸道、尿路、消化道和神经系统副反应轻,不妨碍临床用药。     

Long-term outcome of patients with diffuse proliferative lupus nephritis treated with prednisolone and oral cyclophosphamide followed by azathioprine

The short-term outcome of patients with diffuse proliferative lupus nephritis (DPLN) has improved with advances in immunosuppressive treatment. However, the impact of different immunosuppressive regimens on long-term renal function remains to be defined. This prospective cohort study examined the long-term renal function and disease relapse in adults with biopsy-proven DPLN, significant proteinuria, and hypoalbuminemia, who had been treated with sequential immunosuppression comprising prednisolone and oral cyclophosphamide as induction followed by low-dose prednisolone and azathioprine as maintenance. Sixty-six patients with 68 episodes of DPLN were included, with follow-up of 91.7 +/- 36.7 months. 82.4% achieved complete remission and 39.1% relapsed during follow-up. Patients in partial remission were at higher risk of relapse compared with those in complete remission (hazard ratio 6.2, P < 0.001). Serum creatinine remained stable over time (P = 0.931), while creatinine clearance showed a significant increase with time after treatment (P = 0.032). Three (4.4%) patients had doubling of baseline creatinine, but none reached end-stage renal failure or died. Univariate and mixed model analyses showed that the evolution of long-term renal function was significantly influenced by the chronicity score and creatinine clearance at baseline, and by the renal function at one year after treatment. These data demonstrate the efficacy of sequential immunosuppression in preserving renal function in most Chinese subjects with DPLN. The results also indicate that irreversible renal scarring (as reflected by baseline chronicity score), renal reserve (as reflected by renal function at baseline and one year), and an induction regimen that is effective in preserving the nephron mass are critical determinants of long-term renal outcome.     

Immunoglobulin deficiency in kidney allograft recipients: comparative effects of mycophenolate mofetil and azathioprine

Mycophenolate mofetil (MMF) has commonly been substituted for azathioprine (AZA) in kidney transplantation and has been shown to have a greater effect on T cell function and also B cell function than AZA. Although immunoglobulin deficiency has been investigated in patients treated with protocols that include AZA, it has not extensively been studied in MMF-based immunosuppressive protocols. To evaluate this effect, we conducted a prospective study and recruited 49 patients. The patients received either AZA- (group 1) or MMF- (group 2) based therapy. A total of 17 patients in group 1 and 24 patients in group 2 completed the study. Immunoglobulin levels were evaluated before and in every month after transplantation for a 6-month period. Total infectious episodes were recorded and evaluated after 6 months in both groups. While no significant differences have been found in group 1, there were significant decreases in IgG, M, and A levels in group 2 after 6 months (IgG: 11.6+/-1.5-6.8+/-2.0 g/L, P<0.0001; IgM: 2.20+/-1.40-1.40+/-1.16 g/L, P=0.02; IgA: 1.40+/-0.70-1.07+/-0.86 g/L P=0.03). Two patients (11.7%) in group 1 and 11 patients in group 2 (45.8%) were found to have at least one low level of immunoglobulin (P=0.03). When the infectious complications were evaluated, the mean number of infection episodes in each patient was 1.3+/-1.6 and 0.5+/-0.7 for the MMF and AZA groups, respectively (P=0.06). Recurrent urinary tract infection developed in eight patients and seven of those were in group 2. In group 2, 7 of 11 patients with low immunoglobulin levels had recurrent urinary tract infection (63%), while no patient who had normal immunoglobulin levels developed any recurrent urinary tract infections (P<0.001). After 6 months, MMF was changed to AZA in these seven patients, who had both recurrent urinary tract infections and low immunoglobulin levels. All but one patient was found to have normal immunoglobulin levels after 3 months of conversion and only two episodes of infection were recorded during this period. We suggest that serum immunoglobulin levels can be monitored in patients taking MMF, and conversion from MMF to AZA may be an alternative for patients with low immunoglobulin levels and recurrent urinary tract infections.     

Changes in body composition after glucocorticoid therapy in patients with systemic lupus erythematosus

The aim of this study was to evaluate the changes in body composition after glucocorticoid treatment in patients with systemic lupus erythematosus (SLE). Consecutive SLE patients were recruited for serial measurements (baseline, months 2 and 6) of bone mineral density (BMD) and body composition [bone mineral content (BMC), fat and lean mass] by dual energy X-ray absorptiometry scan after high-dose oral glucocorticoid therapy. Factors correlated with changes in body composition were evaluated. 29 SLE patients were studied (age 39.7 +/- 11.5 years; 83% women with 29% postmenopausal; SLE duration 80.1 +/- 80 months). Fourteen patients (48%) were glucocorticoid-naive. The mean maximum daily dosage of prednisolone was 32.9 +/- 6.5 mg and the cumulative prednisolone dosage in 6 months was 2.7 +/- 0.7 g. At 6 months, a significant drop in BMC of the trunk (-5.0 +/- 2.2%; P = 0.04) and whole body (-1.2 +/- 0.4%; P = 0.002) compared with baseline was observed, and so was the BMD of the hip (-1.7 +/- 0.6%; P = 0.006) and whole body (-0.7 +/- 0.3%; P = 0.01). A significant increase in the fat mass of the trunk (+14.5 +/- 4.1%; P = 0.001) and limbs (+10.0 +/- 3.2%; P = 0.004), but a non-significant drop in lean mass of the trunk (-3.3 +/- 1.8%; P = 0.08) and limbs (-0.8 +/- 2.4%; P = 0.75) also occurred. The changes in whole body BMC correlated significantly with age (rho = -0.51; P = 0.02) and changes in total fat mass (rho = 0.44; P = 0.02) but not with lean mass (rho = -0.21; P = 0.27), gender, body mass index, smoking, prednisolone dosages or changes in BMD. In SLE patients, high-dose glucocorticoids lead to an early and rapid drop in bone mass, which is more serious in older patients and correlates with an increase in body fat.     

Mycophenolate mofetil in high risk IgA glomerulonephritis

Mesangial IgA glomerulonephritis (MIgAGn) is the most common biopsied primary glomerulonephritis worldwide, with a poor long-term prognosis for renal function in over a third of all patients. No proven therapy currently exists for MIgAGn. Recent studies have suggested some benefit with mycophenolate mofetil (MMF), especially in hypertensive patients with kidney failure and proteinuria, though other studies have failed to corroborate these findings. We report eight adult patients with biopsy proven MIgAGn followed in a single hospital. They all received angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. Compassionate use of MMF was based on the presence of clinical and analytical data suggesting a high risk of short- to medium-term progression to chronic renal failure. MMF treatment was stopped after two and three months in two patients who had advanced renal failure at the start of therapy because of disease progression and greater fluid retention. Several months later they both required dialysis and kidney transplantation. The mean duration of MMF therapy in the other six patients was 15 (range: 10-18) months. The mean serum creatinine concentration fell from 1.82 +/- 0.47 to 1.55 +/- 0.41 mg/dl (p = 0.04). Protein loss in 24-hour urine collection fell from 1.95 +/- 1.35 to 0.77 +/- 0.58 g/day (p = 0.02). These results in this low number of patients showed that treatment with MMF in high-riks patients with MIgAGn and early stage kidney failure generally stabilized the disease and reduced proteinuria. MMF was well tolerated and may be of some benefit in a subgroup of patients with MIgAGn and a poor prognosis.     

Mycophenolate mofetil in the treatment of lupus nephritis, in patients with failure, intolerance or relapses after treatment with steroids and cyclophosphamide

Intravenous cyclophosphamide (IVCP) in combination with oral steroids (ST) is the most widely accepted therapy for severe lupus nephritis (LN); however, its side effects, lack of response and relapses, have led to other treatment alternatives. being sought. Mycophenolate mofetil (MMF) has been shown to be effective in these cases. We studied the course over 12 months of 28 patients with LN WHO class III(n=3), IV(n=22) or V(n=3), with 38,1 +/- 11,4 tears of age, proteinuria 4,2 +/- 2,6 g /24 hours and serum creatinine 1,4 +/- 0,8 mg/dL, who, after being initially treated with ST and IVCP, showed no response(n=21), frequent relapses(n=6), or adverse side effects(n=1). All patients were treated with MMF in doses of 1000 to 2000 mg/day combined with ST or cyclosporine for one year. Four patients withdrew from treatment before the end of the follow-up. None of the patients who completed the study showed changes in hematologic parameters. Creatinine and creatinine clearance remained stable. Resulted in a significant improvement; serum albumine (3 +/- 0,8 vs 3,9 +/- 0,5 g/dL) p<0.01, and decreased of proteinuria (4,2 +/- 2,6 vs 1,8 +/- 2,2 g/ 24 hours) p<0.05, complement fractions improvement significantly, C3 and CH50 p<0.05, C4 p<0.01. Antinuclear antibodies (ANA) and anti-DNA antibodies decreased significantly (p<0.05). During follow-up, a reduction in the ST dose was achieved: 18.3 +/- 10,5 vs 10,1 +/- 4,1 mg/24h (p<0.01). Three mild side effects related to MMF were observed and only 1 case required discontinuation of treatment. We concluded that MMF is a useful drug in the treatment and control of lupus nephritis, which also allows for a significant reduction in the dose of ST, with minimal side effects.     

霉酚酸酯预防尸体肾移植急性排斥反应

目的；观察霉酸酯预防尸体肾移植急性排斥反应的疗效及其副反应。方法：共２０例无手术并发症的初次尸肾移植病例，随机分为三组：ＭＭＦ２ｇ／ｄ组１０例，ＭＭＦ１．５ｇ／ｄ组５例，硫唑嘌呤（ＡＺＡ）组５例：各组均同时应用环孢霉素和强的松。定期行相关检查，并常规行移植肾活检。结果：ＭＭＦ治疗组经活检证实的急性排斥发生率较低，ＭＭＦ２ｇ组：无（０／１０），ＭＭＦ１．５ｇ组，１例（１／５）；ＡＺＡ组２例（２／５）     

霉酚酸酯治疗乙型肝炎病毒相关性肾炎的临床观察

目的观察应用霉酚酸酯(MMF)治疗乙型肝炎病毒相关性肾炎的临床疗效及安全性。方法对2000年1月至2005年1月中国医科大学附属盛京医院20例乙型肝炎病毒相关性肾炎患者给予MMF治疗,起始剂量为1.5g/d,尿蛋白降至0.5g/d时剂量减至1.0g/d维持,有乙型肝炎病毒(HBV)DNA复制的给予拉米夫定治疗。治疗前及治疗后2,3,6,9个月检测血常规、24h尿蛋白定量、血清白蛋白、肝功能、肾功能、血脂及HBVDNA定量,并记录不良反应情况。结果治疗后24h尿蛋白量明显减少(P<0.01),血清白蛋白明显上升(P<0.05),Scr明显下降(P<0.05),胆固醇及三酰甘油水平明显降低(P<0.05),未发现病毒复制增加。随访9个月完全缓解9例,总有效率85%。治疗期间未发现严重不良反应。结论MMF用于治疗乙型肝炎病毒相关性肾炎有明显疗效,且耐受性好,未见严重不良反应。     

Conversion to mycophenolate mofetil for modulating recurrent hepatitis C in liver transplant recipients

BACKGROUND: The aim of this study was to analyze the influence of cyclosporine A (CsA) taper in conjunction with mycophenolate mofetil (MMF) therapy on recurrent hepatitis C virus (HCV) in liver transplant patients. PATIENTS AND METHODS: Nineteen liver recipients with serologically and morphologically confirmed recurrent HCV were included in this study. After MMF introduction up to a maximum dose of 2000 mg/day, CsA dose was significantly tapered. In the control group immunosuppression remained unchanged. Allograft function and morphology, viral loads, and renal function were analyzed continuously. RESULTS: MMF treatment was well tolerated without risk of rejection. Allograft fibrosis progressed in 6 patients of the MMF group (66.6%) and none (0%) of the controls at 12-month biopsy (P=0.005). Moreover, aminotransferases and viral loads increased slightly in the MMF-treated patients. Renal function improved significantly (serum creatinine: 239.3+/-90.2 micromol/L vs. 175.8+/-46.0 micromol/L; P=0.008) in the treatment group, while deteriorating (serum creatinine: 156.8+/-44.6 micromol/L vs. 214.8+/-120.1 micromol/L; P=0.06) in the controls. CONCLUSION: MMF introduction allows a safe CsA taper in HCV-positive liver transplant patients and results in significant improvement of renal function. However, there seems to be a risk of marked progression of HCV-induced allograft injury.     

Mycophenolate mofetil in refractory Crohn's disease after failure of treatments by azathioprine or methotrexate

Failure or intolerance of treatments by azathioprine (AZA) or methotrexate (MTX) is an important problem in the maintenance treatment of refractory CD. Results of the alternative use of mycophenolate mofetil (MMF) are conflicting.AIM: To assess the efficacy and tolerance of MMF in patients with refractory CD included in a multicentre and retrospective study.PATIENTS AND METHODS: Twenty patients (5 men, 15 women, median age 33 years) have been enrolled. The disease was located in the small intestine (n=7), colon (n=5) or in both ileon and colon (n=8). Five patients had perineal disease. Neighteen patients had an active CD and 13 of them received steroids (30 mg daily). All of them had been treated by AZA (failure, n=5; intolerance, n=15) and/or MTX (failure, n=12; intolerance, n=6). The dose of MMF was 750 mg to 2 g daily for a median of 4 months (range: 4 days-21 months). Response to MMF was determined according to an Harvey-Bradshaw index<4 and the possibility to taper steroids.RESULTS: Four patients (AZA: failure, n=2; intolerance, n=2; MTX: failure, n=2; intolerance, n=1) achieved remission under MMF. Three of them had an active CD before start of MMF, 1 patient was already in remission. Those 4 patients remained in remission during follow up (10-18 months). One of the 5 patients with perineal involvement achieved a complete closure of perineal fistula. Ten patients had to stop the medication for a median of 4 months (range: 2-12 months) because of inefficiency. Eleven patients had early adverse reactions and 5 of them had to stop the medication within 4 days to 3 months: pancreatitis (n=2), toxidermia (n=2), diarrhea and abdominal pain (n=1).CONCLUSION: In this short cohort of 20 patients with refractory CD, either intolerant or non responder to AZA or MTX, treatment with MMF resulted in only 20% of success. Intolerance to MMF was observed in 25% of patients.