肾上腺皮质激素在肾移植术后肺部感染治疗中的应用研究

目的探讨肾上腺皮质激素(激素)在治疗肾移植术后肺部感染中的应用价值。方法收集2008年1月至2012年6月解放军第281医院肾移植中心收治的78例肾移植术后肺部感染患者的临床资料,所有患者均签署知情同意书,符合医学伦理学规定。肺部感染发生于肾移植术后2～6个月52例,7～18个月15例,18个月以后11例。其中单纯巨细胞病毒(CMV)感染24例,单纯细菌性感染17例,混合性感染28例,病原体不明感染9例。根据患者情况,予调整或停用免疫抑制剂,应用激素及针对病原学进行抗感染治疗,其后根据患者临床症状及肺部计算机断层摄影术(CT)表现,激素逐渐减量。同时予钙剂预防骨质疏松,予抗凝及调脂药物预防血栓形成,予抑酸剂预防消化道溃疡的发生。结果 78例患者中,治愈73例,死亡3例,并发脑出血放弃治疗1例,转院1例。3例死亡病例中,2例死于多器官功能衰竭,1例死于急性呼吸衰竭。2例患者发生急性排斥反应,其中1例患者免疫抑制方案改为抗人T细胞免疫球蛋白(ALG)+MMF+FK506+甲泼尼龙治疗,另1例通过血液透析过渡,免疫抑制方案改为MMF+FK506+甲泼尼龙治疗,均得以成功逆转。发生下肢静脉血栓2例,脑血栓2例,予对症治疗后好转。结论肾移植术后肺部感染的治疗,应在调整免疫抑制剂方案和抗感染治疗的同时配合激素治疗,可取得良好的治疗效果。     

肾移植术后肺部感染28例诊治分析

目的探讨同种异体肾移植术后肺部感染的诊断和治疗经验。方法回顾性分析28例同种异体肾移植术后肺部感染患者的临床资料。结果 28例患者肺部感染发病时间为术后3个月以内6例,术后4～6个月18例,术后6个月以后4例。患者均以发热起病,早期呼吸道症状轻微,未经治疗者易发展为重症肺炎。肺部体征早期多不明显,X线胸片表现常滞后,胸部CT或磁共振成像有助于早期诊断。肾移植术后肺部感染以细菌、巨细胞病毒、真菌感染为主,混合感染常见。经给予联合使用抗感染药物、减少或者撤除免疫抑制剂、静脉应用肾上腺皮质激素(激素)、营养支持治疗,必要时辅以无创通气或者呼吸机辅助呼吸治疗等综合治疗,治愈22例,死亡6例(均为重症肺炎并发急性呼吸窘迫综合征患者)。结论肾移植术后肺部感染病情进展快,发展为重症肺炎病死率高,应及时予胸部CT或磁共振成像检查,同时加强病原体监测,确诊后及早予使用抗感染药物、调整免疫抑制剂剂量、应用激素、营养支持等治疗,以提高治愈率。     

肾移植术后重症肺炎28例报告

目的总结肾移植术后重症肺炎的诊断和治疗体会。方法回顾性分析28例肾移植术后重症肺炎患者的临床资料。结果重症肺炎的发生时间为术后25d至术后10个月，平均3．5个月，其中术后1～6个月发病26例，占总数的93％。临床表现为高热伴进行性呼吸困难。该组经反复检测病原微生物培养、巨细胞病毒（CMV）脱氧核糖核酸（DNA）、CMV免疫球蛋白（Ig）M，24例获得病原学证据（混合性感染20例，单纯细菌感染4例），4例未获得病原学证据。治疗前25例（90％）患者CD4^＋、CD8^＋T淋巴细胞计数减少。治疗方案：停用免疫抑制剂，应用免疫增强剂，联合抗细菌、抗病毒、抗真菌，机械通气，营养支持等综合治疗。22例（79％）治愈，其中20例移植。肾功能正常，2例血清肌酐轻度升高。6例死于急性呼吸窘迫综合征（ARDS），均为CD4^＋、CD8^＋ T淋巴细胞计数持续低水平者，其中2例为细菌＋真菌＋CMV感染者，1例为细菌＋CMV感染者，3例为未明确病原菌患者。结论肾移植术后重症肺炎临床表现缺乏特异性，病原学诊断对指导治疗有重要意义，因此需反复进行病原微生物培养、CMVDNA、CMV IgM检测。促进免疫功能恢复、联合应用抗病原微生物药物、对症和支持治疗是成功救治的关键。     

肾移植术后巨细胞病毒肺炎13例报告

目的：总结肾移植术后巨细胞病毒(CMV)肺炎的防治经验,探讨有效的防治措施。方法：回顾性分析13例行同种异体肾移植术后并发CMV肺炎患者的临床资料。13例均在肾移植术后2～6个月发病,均以发热、干咳起病,胸片检查均有间质性肺炎改变。13例患者中,血CMVPP65抗原阳性9例。治疗措施包括早期抗病毒治疗、撤减免疫抑制剂用量、适时使用机械通气、加强全身支持治疗等。结果：13例患者中,治愈8例(61．5%),好转3例(23．1%),死亡2例。7例术后使用更昔洛韦预防CMV感染的患者,治愈4例,好转2例,死亡1例。结论：肾移植术后加强CMV检测有利于CMV肺炎的早期诊断。术后积极预防CMV感染,早期采取以抗病毒为主的综合治疗可提高治愈率。     

糖皮质激素在治疗肾移植术后巨细胞病毒性重症肺炎中的作用

目的探讨糖皮质激素在治疗肾移植术后巨细胞病毒(CMV)性重症肺炎中的作用。方法2002年1月至2004年10月发生肾移植后CMV性重症肺炎26例。选取2002年1月至2003年3月之间发病的12例为A组,2003年4月至2004年10月之间发病的14例为B组。发生CMV性重症肺炎后,A组治疗方案为:停用环孢素A(或他克莫司)和霉酚酸酯等免疫抑制剂,应用更昔洛韦等抗病毒药物,防治其它合并的感染,全身支持疗法,吸氧或呼吸机辅助通气等措施。B组除上述同样治疗措施外,还常规静脉应用甲泼尼龙(MP),起始剂量为120～150mg/d,3～5d后减量至80mg/d维持,当临床表现好转后再减量至40mg/d,应用时间为8～21d,平均12d。以后改为口服泼尼松维持。比较2组的治疗效果。结果A组应用呼吸机治疗9例(75%),其中死亡7例(58.33%),2例移植肾功能丧失,需透析治疗(16.67%);B组应用呼吸机治疗的4例(28.57%),其中死亡2例(14.29%),患者均无移植肾功能丧失。两组患者需用呼吸机治疗的几率和死亡率比较,B组均低于A组,差异均有统计学意义(P值分别为0.047和0.038)。B组患者中,均未出现激素相关的严重不良反应。结论应用适当剂量的甲泼尼龙,能有效减轻肾移植后CMV性重症肺炎的肺部炎症反应,并能减少因停用其它免疫抑制剂导致的移植肾排斥反应,降低死亡率和避免移植肾功能的丧失。     

肾移植术后巨细胞病毒肺炎的诊治

目的：探讨肾移植术后巨细胞病毒（CMV）肺炎的发病特点及诊治方案。方法：回顾分析9例肾移植术后并发CMV肺炎患者的临床资料。结果：治愈6例,2例有效好转,但后因经济困难放弃治疗,1例无效而死亡．结论：肾移植术后3～6个月为CMV感染易感期,术前,术后加强CMVPP65抗原及CMVIgM监测对CMV肺炎的预防及早期诊断有帮助。尽早诊断、减少或停用免疫抑制剂、早期足量长疗程抗病毒治疗、加强营养、适时机械辅助砰吸的综合治疗可提高治愈率。     

肾移植术后机会感染的预防

目的探讨预防肾移植术后机会感染的有效方法。方法同种异体肾移植患者30例,术后常规予含他克莫司(tacrolimus,FK506)或环孢素(ciclosporin,CsA)三联抗排斥治疗,术后6个月内,CD4+计数420×106/L(正常参考值420×106/L～890×106/L)和(或)CD4+/CD8+比值0.82(正常参考值0.82～1.69)。30例随机分为预防治疗组(预防组)、免疫抑制剂减量组(减量组)和对照组3组,每组各10例。预防组在维持原治疗方案的同时予复方磺胺甲唑(SMZ-TMP)每日2片,连用1个月,7例加用更昔洛韦0.5g/d,连用14d,3例加用缬更昔洛韦治疗,900mg/d,连用3个月;减量组根据FK506或CsA血药浓度调整剂量;对照组维持原治疗方案。术后1年为观察终点。结果除减量组4例患者自行退出外,其余患者均完成实验。预防组无发生机会感染,1例出现一过性肾功能损害。对照组1例于术后92d感染巨细胞病毒(cytomegalovirus,CMV)病、另1例术后116d确诊卡氏肺孢子虫肺炎,经治疗痊愈。减量组2例分别于减量后13d、21d发生排斥反应,经甲泼尼龙冲击逆转,另1例于减量后20d经病理证实亚临床排斥反应。结论肾移植术后CD4+计数和(或)CD4+/CD8+比值较低的患者易发生机会感染,予预防治疗可有效降低机会感染的几率,且安全性好。免疫抑制剂减量存在发生排斥反应的风险。     

公民逝世后器官捐献供肾移植肺部感染诊治研究

目的分析DCD供肾移植肺部感染的特点及诊治效果。方法回顾性分析2011年6月至2014年12月施行的DCD供肾移植69例,以同期的尸体供肾移植129例作为对照组。所有受者均采用抗体诱导+他克莫司(TAC)+麦考酚酯(MMF)+泼尼松(Pred)四联免疫抑制方案。分析总结DCD供肾移植术后肺部感染特征,治疗效果。结果随访6~24个月,DCD组和SCD组受者肺部感染总体发生率分别为17.4%和33.3%,移植术后半年内肺部感染发生率分别为15.9%和15.5%;DCD组肺部感染死亡3例,SCD组死亡4例。病原体的种类主要为卡氏肺囊虫、CMV;肺部感染治疗期间急性排斥反应发生各为3例和4例;肺部感染发生同受者DGF状态、感染前使用ATG相关,同供体携带病原体无显著性关联;肺部感染治疗前后受者移植肾功能无明显差异。结论 DCD供肾移植术后肺部感染发生率同尸体供肾移植相当,DGF和T细胞清除剂使用时主要诱因,经积极治疗后可以获得良好的结局。     

肾移植早期快速激素减量安全性分析

目的观察肾移植受者早期快速激素减量的安全性。方法 108例肾移植受者,在含肾上腺皮质激素(激素)的常规三联免疫抑制方案的基础上,分别接受抗胸腺细胞免疫球蛋白(ATG)或抗CD25单抗诱导治疗,于肾移植术后1个月末泼尼松减量至5～10 mg/d。统计术后1、2和3年人/肾存活率,术后1年内的急性排斥反应发生率、移植后感染发生率;记录术后1、6、12个月泼尼松的用量及环孢素(CsA)、他克莫司(FK506)、麦考酚吗乙酯(MMF)的用量,随访期间监测血压、血清肌酐(Scr)、空腹血糖水平。结果受者术后1、2和3年人/肾存活率分别为98%/95%、96%/96%和93%/93%。术后1年急性排斥反应发生率为13%,移植后感染发生率为13.9%。术后12个月内,肾移植受者CsA、FK506、MMF平均用量呈下降趋势。术后1、3、6、12个月泼尼松用量分别为(9.26±2.11)mg/d、(7.42±2.20)mg/d、(6.15±1.94)mg/d、(6.24±2.18)mg/d。术后1年血清肌酐水平为(100±23)μmol/L,收缩压为(127±10)mmHg,舒张压为(81±6)mm-Hg,空腹血糖水平为(5.35±1.44)mmol/L。结论在小剂量抗体诱导、保证钙调磷酸酶抑制剂(CNI)目标浓度,保证机体处于足量免疫抑制的情况下,肾移植术后1个月内快速减少激素至5～10mg/d,移植肾功能正常稳定,同时有助于减少激素不良反应,减少移植后近期感染风险,安全性良好。     

麦考酚钠肠溶片在肾移植术后早期治疗中的有效性和安全性

目的 评估麦考酚钠肠溶片(EC-MPS)在中国肾移植术后早期免疫抑制治疗中的有效性是否与吗替麦考酚酯(MMF)相当,并对其安全性进行评价.方法 采用多中心、前瞻性、随机、双盲、双模拟和平行对照研究.在肾移植术后0～48 h内,将符合标准的受者随机分成EC-MPS组和MMF组.分别用EC-MPS和MMF治疗6个月,观察其有效性和安全性.结果 肾移植术后6个月内,EC-MPS组受者发生急性排斥反应、移植肾功能丧失和死亡的总发生率(14.3%)有低于MMF组(20.3%)的趋势,但两组比较,差异无统计学意义(P>0.05).两组不良反应总的发生率(66.7%和66.0%)也较为接近.但EC-MPS组重度感染和重度肺部感染的发生率略低于MMF组,因严重胃肠道不良反应而导致药物减量或停药的受者比例也略低于MMF组,但差异均无统计学意义(P>0.05).结论 EC～MPS在中国肾移植术后早期对受者的免疫抑制治疗中,其有效性与MMF相等.并且具有良好的安全性.     

Improvement of acute and chronic renal dysfunction in liver transplant patients after substitution of calcineurin inhibitors by mycophenolate mofetil

BACKGROUND: Renal dysfunction caused by treatment with the calcineurin inhibitors (CNI) is a major problem in the long-term course after liver transplantation. PATIENTS: In 22 liver graft recipients with renal dysfunction and stable graft function between 3 weeks and 12 years after transplantation, CNI were substituted by MMF at a final dose of 1.5-3 g/day between October 1996 and October 1998. METHODS: In a prospective non-randomized study, the development of renal function, the side effects of MMF medication, and the stability of liver function were analyzed for a mean follow-up of 15 months. Results. (1) MMF was withdrawn in four patients for major side effects between 1 and 7 months after study entry; eight patients had minor side effects. (2) Six months after study entry, renal function had improved in 17 of the 22 study patients; mean serum creatinine +/-SD (micromol/L) was 201+/-77 at entry and 153+/-65 after 3 months (P<0.001). (3) Improvement occurred in 11 of 15 patients with creatinine elevation > or =12 months and in 6 of 6 patients with creatinine elevation < or =6 months. (4) One patient developed transient liver dysfunction and a second required retransplantation for progressive cholestasis but without signs of rejection. CONCLUSIONS: In patients who undergo liver transplantation, substitution of CNI by MMF leads to improvement of acute as well as chronic renal dysfunction in most cases. Side effects of MMF may be limiting in some patients, and the immunological consequences remain to be studied.     

Conversion to sirolimus-based immunosuppression in maintenance liver transplantation patients.

Sirolimus (SRL) has been proposed to replace calcineurin inhibitors (CNI) in case of CNI-induced toxicity. The aim of this study was to evaluate the efficacy and safety of conversion from CNI to SRL in maintenance liver transplantation (LT) patients. Between 2002 and 2006, conversion was performed in 48 patients (17 female, 31 male; mean age 57 +/- 10 yr) after a median delay of 19.4 months (range 0.2-173 months) after LT. Indication for conversion was renal impairment (RI) (78%), CNI neurotoxicity (13%), or post-LT cancer (9%). Median follow-up was 22.6 +/- 11 months. Median SRL dosage and trough levels were 2.4 +/- 1.3 mg and 8.1 +/- 2.7 microg/L. Immunosuppression consisted of SRL alone (33%), or SRL + mycophenolate mofetil (MMF) (39%), SRL + prednisone (15%), SRL + CNI (4%), or SRL + MMF + prednisone (8%). Mean glomerular filtration rate (GFR) improved from 33 to 48 mL/minute in patients with severe RI (P = 0.022) and from 56 to 74 mL/minute in patients with moderate RI (P = 0.0001). After conversion, main complications were albuminuria (36%), hyperlipidemia (49%), dermatitis (14%), edema (14%), oral ulcers (12%), joint pain (4%), infection (2%), and pneumonia (2%). Acute rejection (AR) occurred in 17% of the patients. SRL was withdrawn in 17% of the patients. In conclusion, conversion from CNI to SRL is safe and is associated with significant renal function improvement.     

肝移植后因药物不良反应暂停及转换钙调磷酸酶抑制剂的单中心经验

目的 研究肝移植术后暂停及转换钙调磷酸酶抑制剂(CNI)对控制感染和改善受损肾功能的作用.方法 回顾性分析单中心施行的947例原位肝移植的资料,分为2个阶段,第1阶段(2002年1月至2007年12月)有234例肝移植术后发生感染的患者,第2阶段(2008年1月至2010年12月)有101例.2个阶段共有329例受者因CNI肾毒性而造成肾功能损害,其中将CNI转换为SRL者40例(转换组),其余289例采取CNI减量+吗替麦考酚酯(MMF)加量方案(减量组).结果 肝移植术后存活超过1、3和5年者CNI的应用率分别为95.8%、95.3%和97.5%.第2阶段共有17例受者短期停用免疫抑制剂,停药的主要原因是细菌(部分合并真菌)感染(88.2%);2个阶段共有48例患者将CNI转换为SRL,换药主要原因是肾功能损害(83.3%).第2阶段感染患者中短期暂停CNI者15例,占14.9%(15/101),CNI暂停后感染控制的有效率为73.3%(11/15),排斥反应发生率为6.7%(1/15).第2阶段感染患者的累积存活率明显高于第1阶段(P＜0.05).转换组CNI转换前肾小球滤过率为(0.82±0.24)ml/s,CNI转换后6周时为(1.28±0.31)ml/s,6个月时为(1.36±0.32)ml/s,转换后6周和6个月时高于转换前(P＜0.05).CNI调整后6个月时,转换组患者存活率为85.0%,减量组为83.7%(P＞0.05).结论 肝移植术后患者发生感染及肾功能损害时可采取CNI减量甚至短时间停用CNI,或转换使用SRL,此方案是安全、有效的.

Abstract：

Objective To report the results of a single-center, retrospective study on the effect of calcineurin inhibitors (CNI) withdraw for controlling infections and conversion to sirolimus (SRL)for ameliorating renal dysfunction. Methods A total of 947 liver transplant cases from 2002 to 2010were divided into two eras (Jan. 2002 to Dec. 2007 and Jan. 2008 to Dec. 2010). There were 234cases of infections after liver transplantation (LT) in the first era and 101 cases in the second era. And of 329 cases of CNI-related renal dysfunction after LT in two eras, 40 cases (converting group) had converted CNI to SRL, while 289 cases (reducing group) adopted protocol of CNI reducing and mycophenolate mofetil (MMF) raising. Results CNI-based IS took up 95.8 %, 95. 3 %, 97. 5 % of the IS protocols with recipient survival time longer than 1, 3, and 5 years. The primary cause for CNI withdraw was infection (88. 2 %, 15/17) in the second era, and renal dysfunction for conversion to SRL in the two eras (83. 3 %, 40/48). In the second era, 14. 9% (15/101) of the cases of infections after LT experienced CNI withdraw. Of the 15 patients, 11 had effectively controlled the infection (77. 3 %) while rejection rate was 6. 7 % (1/15). The cumulative survival rate of the second era was significantly higher than the first era (P＜0. 05). The glomerular filtration rate (GFR) of converting group at 6th week and 6th month was statistically elevated as compared with that before conversion,respectively (1.28 ± 0. 31, 1.36 ± 0. 32 mL/s vs. 0. 82 ± 0. 24 mL/s, P＜0. 05). Six months after CNI adjustments, survival rate of converting group and reducing group was 85. 0% and 83. 7 %,respectively (P＞0. 05). Conclusion Reducing or even short-term withdraw of CNI may allow the better control of infections after LT, and the conversion from CNI to SRL can ameliorate the CNIrelated nephrotoxicity. These individually tailored IS protocols will benefit the long term survival for LT.     

Predictors of improvement in renal function after calcineurin inhibitor withdrawal for post-liver transplant renal dysfunction

BACKGROUND: Renal dysfunction after liver transplantation is a major management problem. Predictors of improvement in renal dysfunction after calcineurin inhibitor therapy (CNI) withdrawal and replacement with either mycophenolate mofetil (MMF) or azathioprine (AZA) have not previously been examined. METHODS: Retrospective analysis of 33 post-transplant patients with creatinine clearance (CrCl) below 50 mL/min who were changed from CNI to either MMF or AZA. Following CNI withdrawal patients were divided into two groups: those with improved CrCl after switching and those without, to identify the variables associated with improved renal function. RESULTS: Variables associated with improved CrCl were: absence of hypertension or diabetes, shorter time between transplantation and switch, deterioration in CrCl in months prior to switch and treatment with MMF (compared with AZA). CONCLUSIONS: Our findings suggest CNI withdrawal should be targeted to a subgroup of patients whose renal function is most likely to improve.     

Mycophenolate Mofetil Monotherapy for Severe Side Effects of Calcineurin Inhibitors Following Liver Transplantation

Withdrawal of calcineurin inhibitors (CNI) followed by mycophenolate mofetil (MMF) monotherapy after liver transplantation (LT) remains controversial due to the increased risk of acute rejection and graft loss. The aim of the present study, performed in a large cohort of liver-transplanted patients with severe CNI-induced side effects, was to assess renal function recovery, and safety in terms of liver function, of complete CNI withdrawal and replacement by MMF monotherapy. Fifty-two patients treated with MMF monotherapy for CNI-induced toxicity were analyzed. Mean estimated glomerular filtration rate (eGFR) increased significantly during the period of MMF monotherapy, from 37 ± 10 to 44.7 ± 15 mL/min/1.73 m² at 6 months (p = 0.001) corresponding to a benefit of +17.4% in renal function. eGFR stabilized or improved in 86.5%, 81% and 79% of cases, and chronic renal dysfunction worsened in 13.5%, 19% and 21% of cases, at 6, 12 and 24 months after CNI withdrawal, respectively. Only two patients experienced acute rejection. MMF monotherapy may be efficient at reversing/stabilizing CRD, and appears relatively safe in terms of liver graft function in long-term liver-transplanted patients. However, clinicians must bear in mind the potential risk of rejection and graft loss, and should be very cautious in the management of such 'difficult-to-treat patients'.     

Effects of mycophenolate mofetil introduction in liver transplant patients: results from an observational,non‐interventional,multicenter study (LOBSTER)

The benefits of calcineurin inhibitor (CNI)‐sparing regimens on renal function following liver transplantation (LT) have been demonstrated in clinical studies. This observational study assessed the real‐life effects of mycophenolate mofetil (MMF) introduction in LT patients. Four hundred and ninety‐seven patients in whom MMF was introduced according to local standards or clinical considerations were entered. Patients were grouped by time between transplantation and start of MMF (start of study): Group A (n = 263): ≤6 d; Group B (n = 64): >6 d to ≤1 month; Group C (n = 74): >1 month to ≤1 yr; and Group D (n = 96): >1 yr. CNI sparing occurred in all groups, particularly in Groups C and D. Mean MMF doses at 12 months were 1202.7, 1363.5, 1504.7, and 1578.1 mg/d, respectively, in Groups A–D. At introduction of MMF, median glomerular filtration rate was 73.3, 81.7, 62.7, and 53.7 mL/min/1.73 m² in Groups A–D. At 12 months, this decreased to 66 mL/min/1.73 m² in Groups A and B, remained stable in Group C, and increased in Group D (64.8 mL/min/1.73 m²). Serious adverse drug reactions were lowest in Group D. In conclusion, MMF with a subsequent decrease in CNI was well tolerated and improved renal function even years after transplantation. A more forceful MMF dosing strategy with greater CNI sparing may further improve renal function.     

Evolution of immunoglobulin and mannose binding protein levels after renal transplantation: association with infectious complications.

Hypogammaglobulinemia (hypo-Ig) and low mannose binding protein (MBP) levels might be involved in the infectious risk in renal transplantation. In 152 kidney transplant recipients treated with calcineurin inhibitors (CNI) and mycophenolate mofetil (MMF), during the first year, we prospectively recorded the incidence of hypogammaglobulinemia, and low MBP levels. Their influence on infectious complications was evaluated in 92 patients at 3 and 12 months (T3 and T12). The proportion of deficiency increased significantly: hypo-IgG: 6% (T0), 45% (T3), and 30% (T12) (P < 0.001); hypo-MBP: 5%, 11%, and 12% (P = 0.035). Hypo-IgG at T3 was not associated with an increased incidence of first-year infections. A significantly higher proportion of patients with combined hypogammaglobulinemia [IgG+ (IgA and/or IgM)] at T3 and with isolated hypo-IgG at T0 developed infections until T3 compared with patients free of these deficits (P < 0.05). Low MBP levels at T3 were associated with more sepsis and viral infections. Hypogammaglobulinemia is frequent during the first year after renal transplantation in patients treated with a CNI and MMF. Hypo-IgG at T0 and combined Igs deficts at T3 were associated with more infections. MBP deficiency might emerge as an important determinant of the post-transplant infectious risk.     

Long-term mycophenolate mofetil monotherapy in combination with calcineurin inhibitors for chronic renal dysfunction after liver transplantation

BACKGROUND: Calcineurin inhibitors (CNIs) are the first-line immunosuppressive agents administered after liver transplantation, but they cause renal impairment. Two recent randomized trials report cellular rejection and liver graft loss when mycophenolate mofetil (MMF) monotherapy was used as a renal-sparing agent. Our experience with MMF in the same setting but with longer follow-up is described. METHODS: In 45 patients with serum creatinine more than 120 micromol/L or creatinine clearance less than 50 mL/min, 2 g MMF per day was administered (median 29 months, 1-49 months) either as monotherapy (with all other immunosuppression withdrawn in 1 month) in 16 patients (group I) or in combination with low-dose CNI (trough tacrolimus 相似文献   

Conversion to Sirolimus in Kidney-Pancreas and Pancreas Transplantation

Reports on the use of sirolimus (SRL) in pancreas transplantation are still limited. The aim of this study was to evaluate the outcome of SRL conversion in pancreas transplant patients. Among 247 patients undergoing simultaneous kidney-pancreas or solitary pancreas transplantation, 33 (13%) were converted to SRL. The reasons for conversion were calcineurin inhibitors (CNI) nephrotoxicity (n = 24; 73%), severe neurotoxicity owing to CNI (n = 1; 3%), severe and/or recurrent acute rejection episodes (n = 7; 21%), gastrointestinal (GI) side effects of mycophenolate mofetil (MMF; n = 5; 15%), and hyperglycemia (n = 4; 12%).Before conversion, all patients were maintained on a CNI, MMF, and low-dose steroids. They were gradually converted to SRL associated with either CNI or MMF withdrawal. Sixty-three percent (n = 15) of patients who were converted owing to CNI nephrotoxicity, showed stable or improved renal function. At 12 months after conversion, serum creatinine levels were significantly decreased in this group (2.2 ± 0.5 vs 1.6 ± 0.3 mg/dL; P = .001) and C-peptide values increased (2.9 ± 1.1.1 vs 3.1 ± 1.3 nmol/L; P = .018). The only patient with leucoencephalopathy showed improved neurologic status after SRL conversion. All patients converted to SRL because of GI side effects of MMF showed improvements, and none of those converted because of hyperglycemia experienced improvement. There were no episodes of acute rejection after conversion.We concluded that conversion to SRL in pancreas transplantation should be considered an important alternative strategy, particularly for CNI nephrotoxicity and neurotoxicity, and in cases of severe diarrhea due to MMF.     

Calcineurin-inhibitor-sparing immunosuppressive protocols

Calcineurin inhibitors (CNI) have played an important role in improving graft survival. However, the balance between preventing immunologic allograft losses and the management of CNI-related nephrotoxicity is still an issue in renal transplantation. There are three major CNI-sparing strategies. CNI MINIMIZATION: The advent of mycophenolate mofetil (MMF) allows cyclosporine (CsA) reduction to ameliorate renal function in patients with chronic renal allograft dysfunction, without increasing acute rejection rates. In combination with mTOR inhibitors, very low CNI levels may be sufficient to prevent acute rejection. However, in this association, CNI nephrotoxicity is magnified by pharmacokinetic interaction. CNI WITHDRAWAL: CNI withdrawal has been attempted in regimens containing MMF or sirolimus (SRL). Introduction of MMF in patients with chronic allograft nephropathy (CAN) followed by CNI withdrawal resulted in stabilization or improvement of renal function and hypertension profile, although there is some risk of acute rejection. In regimes based on SRL, CNI withdrawal is a safety strategy, achieving a sustained improvement of renal function, histology, and graft survival. There is not consensus at all whether MMF should be added or not in patients converted from CNI to mTOR inhibitor. CNI AVOIDANCE: Polyclonal-based regimens with MMF and steroids have shown acceptable acute rejection rates, but high rates of cytomegalovirus (CMV) and opportunistic infections. Conversely, anti-IL-2R in combination with MMF and steroids resulted in 50% incidence of acute rejection, thus suggesting that CNI avoidance is not feasible in a regimen based on MMF. Alternatively, a protocol based on anti-IL-2R induction therapy combined with SRL, MMF, and prednisone has shown an efficient prevention of acute rejection, higher creatinine clearance and lower rate of CAN in comparison with a group treated with CNI. New strategies using costimulation blockade may help in the development of safe CNI-free regimens. In summary, in renal transplantation the new immunosuppressive medications have made feasible old aspirations such as minimization, withdrawal, or even avoidance of CNI.