撤除激素的肾移植免疫抑制方案研究

目的观察在应用巴利昔单抗的基础上,早期撤除激素的免疫抑制剂方案临床效果。方法21例肾移植患者在应用巴利昔单抗的同时联合他克莫司(FK506)和霉酚酸酯(MMF),早期撤除激素,随访观察急性排斥发生情况,以及对血糖血脂代谢的影响等。结果巴利昔单抗联合FK506和MMF,早期撤除激素,使急性排斥发生率明显降低同时,也降低高血糖、高血脂等代谢紊乱发生率。结论应用巴利昔单抗同时联合强有力的免疫抑制剂FK506和MMF,调整药物FK506浓度于治疗窗范围,早期撤除激素,是安全有效的方案。     

多药耐药基因多态性与心脏移植术后环孢素肾毒性的相关性分析

目的：探讨多药耐药（ MDR1）基因多态性与心脏移植术后患者环孢素（ CsA）治疗所致肾损害的相关性。方法选取2004年1月至2012年12月在首都医科大学附属北京安贞医院行心脏移植术、术后应用含CsA的免疫抑制方案治疗并至少随访12个月的患者作为研究对象,根据CsA治疗后是否出现肾损害分为肾损害组和无肾损害组。应用患者心脏移植术后检测CsA全血浓度时留取血样提取白细胞基因组DNA。根据HapMap数据库提供的位点信息,采用基质辅助激光解析电离飞行时间质谱（ MALDI-TOF MS）技术测定MDR1基因16个标签SNP位点的基因型和等位基因频率。应用dbSNP数据库进行SNP位点等位基因频率的比对,应用非条件性二元Logistic回归分析方法分析SNP多态性与CsA所致肾损害的相关性。结果共入选65例患者。肾损害组19例,男性17例,女性2例;年龄18-59（44±13）岁。无肾损害组46例,男性39例,女性7例;年龄14-71（42±15）岁。2组患者年龄、性别分布差异均无统计学意义（均P〉0.05）。MALDI-TOF MS检测获得的2组患者16个tag SNP位点的等位基因频率与dbSNP数据库数据比较以及2组之间比较,差异均无统计学意义（均P〉0.05）。经非条件性二元Logistic回归分析,MDR1基因16个Tag SNP位点的基因型频率与肾损害组患者CsA肾毒性的发生无明显相关性。结论 MDR1基因多态性与心脏移植受者CsA治疗所致肾损害无明显相关性。     

A network meta-analysis of the efficacy of belatacept,cyclosporine and tacrolimus for immunosuppression therapy in adult renal transplant recipients

Belatacept is a first in-class co-stimulation blocker developed for primary maintenance immunosuppression following renal transplantation. The objective of this study was to estimate the efficacy of belatacept relative to tacrolimus and cyclosporine among adults receiving a single kidney transplant.

A systematic review was conducted of randomized clinical trials (RCTs) published between January 1990 and December 2013 using EMBASE, MEDLINE, the Cochrane Central Register of Controlled Trials, and unpublished study reports from two belatacept RCTs. Bayesian network meta-analysis (NMA) methods were used to compare the efficacy measures, mortality, graft loss, acute rejection and glomerular filtration rate (GFR). Heterogeneity was quantified using statistical metrics and potential sources were evaluated using meta-regression and subgroup analysis.

A total of 28 RCTs comparing tacrolimus with cyclosporine, and three comparing belatacept with cyclosporine, were identified.

All three agents provided comparable graft and patient survival, despite a higher risk of acute rejection associated with belatacept and cyclosporine. Belatacept was associated with significant improvement in GFR versus cyclosporine. Compared with tacrolimus, this difference was clinically meaningful yet statistically non-significant. The probability of being the best treatment was highest for belatacept for graft survival (68%), patient survival (97%) and renal function (89%), and highest for tacrolimus for acute rejection (99%).Variability in donor, recipient, and trial characteristics was present in the included RCTs; however, minimal statistical heterogeneity was detected in the analysis of acute rejection, graft or patient survival, and none of the characteristics were found to be significantly associated with relative effect. Although the direction of effect of immunosuppressants on GFR was consistent across RCTs, precise estimation of its magnitude was limited by a small number of RCTs and heterogeneity in relative effect sizes.

Clinicians often seek an alternative to CNIs due to their nephrotoxic effects. The results of this indirect comparison indicate that belatacept is an effective immunosuppressive agent in renal transplantation among adults.     

肾移植术后吗替麦考酚酯替换硫唑嘌呤的临床分析

目的 :观察肾移植后吗替麦考酚酯 (MMF)替换硫唑嘌呤 (Aza)的安全性及其临床效果。方法 :回顾分析16例由Aza转换为MMF患者的临床资料。4例因肝功能损害而改用MMF,7例肾功能损害 ,5例应患者要求而换用MMF。结果 :4例肝功能损害者肝功能均恢复正常 ,7例肾功能损害者2例逆转 ,4例肌酐 (SCr)下降但未能恢复正常 ,1例继续恶化恢复血液透析。2例不良反应包括原有贫血明显加重 ,1例腹泻。结论 :Aza可以安全替换为MMF。因环孢素 (CsA)加Aza引起肝功能损害者 ,换用MMF ,减少CsA用量 ,肝功能可望恢复。MMF对部分慢性排斥反应可能有效     

The use of mycophenolate mofetil in liver transplant recipients

Mycophenolate mofetil is an important drug in the modern immunosuppressive arsenal. Mycophenolate mofetil is the semisynthetic morpholinoethyl ester of mycophenolate acid. Mycophenolate acid prevents T and B cell proliferation by specifically inhibiting a purine pathway required for lymphocyte division. This paper extensively reviews the experience of mycophenolate mofetil use in liver transplant recipients. In randomised trials, mycophenolate mofetil decreased the rate of acute rejection after liver transplantation, without a significant increase of septic complications. However, so far, there are no data indicating that mycophenolate mofetil increases liver transplant patient or graft survivals. Mycophenolate mofetil is interesting because of its particular side effects profile, which is very different from the other immunosuppressants. The absence of mycophenolate mofetil nephrotoxicity is of specific interest in liver recipients with impairment of renal function. The monitoring of mycophenolate acid area under the concentration time curve might be interesting to limit side effects and provide better clinical efficacy but the exact role of mycophenolate acid monitoring in liver recipients has yet to be further evaluated in large series.     

糖尿病肾病肾移植受者术后血环孢素A浓度的特点分析

目的探讨糖尿病肾病肾移植受者术后血环孢素A(CsA)浓度的特点。方法采用酶增强免疫分析法(Emit),对34例(糖尿病肾病17例)肾移植受者全血中CsA的谷浓度(C0)和服药后2 h的峰浓度(C2)进行监测,筛除出现肝、肾毒性或排斥反应的数据,并按术后时间进行分组对比分析。结果糖尿病与非糖尿病肾病肾移植术后第1、2月CsA的C0值分别为(214±84)、(175±46)和(251±85)、(209±74)ng/ml,C2值分别为(1087±471)、(963±326)和(1570±600)、(1543±401)ng/ml,2组间差异有统计学意义(P<0.05)。其余月份2组间C0和C2差异无统计学意义(P>0.05)。结论糖尿病肾病肾移植受者术后1～2个月内C0和C2宜控制在(120～250)ng/ml和(550～1500)ng/ml范围内,并随术后时间的延长而逐渐下降,避免毒性和排异反应。     

Pharmacokinetic interactions between microemulsion formulated cyclosporine A and diltiazem in renal transplant recipients

Objective: Bilateral cyclosporin A (CsA) and diltiazem pharmacokinetic interactions have previously been investigated, however, not with the new microemulsion preconcentrate formulation of CsA (Sandimmun Neoral). In addition, the pharmacokinetic effects on the pharmacological active metabolites of diltiazem have not previously been investigated. We performed a pharmacokinetic interaction study in renal transplant recipients, measuring both unmetabolised CsA and diltiazem in addition to three of the main metabolites of diltiazem (M_A, M₁, M₂). Methods: Nine CsA-treated renal transplant patients were treated with diltiazem, 90–120 mg b.i.d., for 4 weeks. Pharmacokinetic investigations were performed both before and at the end of the diltiazem treatment period. Six non-CsA-treated renal transplant patients served as controls of CsA interactions with diltiazem and its metabolites. Results: Diltiazem treatment resulted in a significant mean increase in the area under the concentration–time curve (AUC) for CsA of 51(8)% (P < 0.008) and a peak concentration (C_max) of 34(8)% (P < 0.05), without altering time to peak concentration (t _max). CsA, however, did not significantly influence diltiazem pharmacokinetics, though two of the metabolites (M₁ and M₂) tended to be increased. Conclusions: Diltiazem interacts significantly with the pharmacokinetics of CsA in the new microemulsion formulation. Microemulsion-formulated CsA, however, did not show significant interaction with diltiazem pharmacokinetics. Received: 21 September 1998 / Accepted in revised form: 18 February 1999     

PXR基因多态性与心脏移植术后稳定期环孢素血药浓度的相关性

目的：探讨心脏移植患者术后口服免疫抑制剂环孢素的血药浓度与PXR基因多态性的相关性。方法：应用飞行时间质谱技术对59例心脏移植术后稳定期患者的PXR基因型进行检测,全自动化学免疫分析仪测定环孢素的血药浓度,并通过统计学分析PXR各单核苷酸多态性（SNP）位点基因型对环孢素血药浓度的影响。结果：PXR基因筛选出的8个Tag SNP位点次要等位基因频率（MAF）与NCBI的dbSNP数据库中中国人的数据相近。对于59名稳定期心脏移植患者PXR基因8个Tag SNP中,仅携带PXR rs1523127（C 24381 A）位点AA型基因的患者血药浓度及校正血药浓度明显低于CA型,CA型又低于CC型患者,差异均具有统计学意义（P＜0.05）。其他7个Tag SNP rs3814056T＞G、rs7643645A＞G、rs11917714C＞T、rs2276705C＞A、rs2472681T＞C、rs2472682C＞A、rs4440154C＞T各基因型组间环孢素血药浓度的差异均无统计学意义。结论：PXR rs1523127（C 24381 A）基因型与心脏移植稳定期患者环孢素血药浓度显著相关,提示该SNP可能会在环孢素个体化用药中发挥重要作用。     

合用他克莫司或环孢素对霉酚酸酯及其代谢产物药动学的影响

目的比较合用他克莫司(FK506)与合用环孢素(Cs A)时霉酚酸酯(MMF)及其代谢产物的药动学差异。方法 20例服用MMF肾移植患者分为2组,分别为合用FK506组或合用Cs A组,于服药前和服药后共11个时间点采取外周静脉血,采用高效液相色谱法测定血浆中MMF及其代谢产物霉酚酸葡萄糖苷(MPAG)和霉酚酸酰基葡萄糖苷(Ac MPAG)浓度,计算药动学参数并进行比较。结果与FK506组相比,Cs A组霉酚酸(MPA)C0较低(1.58 vs 3.40 ng·m L-1),且代谢产物Ac MPAG的C0、Cmax和AUC0¹2 h也显著低于FK506组(C0 0.20 vs 0.45 ng·m L-1,Cmax 0.41 vs 0.72 ng·m L-1,AUC012 h也显著低于FK506组(C0 0.20 vs 0.45 ng·m L-1,Cmax 0.41 vs 0.72 ng·m L-1,AUC0¹2 h 3.04 vs 6.50ng·h·m L-1),2组间MPAG药动学参数差异无统计学意义。结论合用其他免疫抑制剂可能会对MMF及其代谢产物Ac MPAG的药动学产生显著影响。     

肾移植术后合并重型肝炎临床探讨

目的:探讨肾移植术后重型肝炎病因、治疗及预防。方法:对330例肾移植患者所发生的8例肾移植术后重型肝炎患者的临床资料进行分析。结果:6例患者为慢性重型肝炎,2例患者为急性重型肝炎。病毒学检测均有乙肝病毒感染且病毒处于复制状态,8例均于移植术前感染,经积极治疗后,6例患者死亡,好转2例。结论:重型肝炎是肾移植术后严重的并发症之一,主要病因为乙型肝炎病毒及免疫抑制剂的毒性,术后密切监测肝功能及环孢素A(CsA)浓度、HBVDNA的滴度,早期发现、早期治疗,加强预防,提高人肾存活率     

吗替麦考酚酯胶囊和麦考酚钠肠溶片在早期肾移植患者中的药动学

目的：探讨肾移植术后早期患者口服吗替麦考酚酯胶囊（MMF）和麦考酚钠肠溶片（EC-MPS）的药动学特点,为临床合理用药提供依据。方法：选取26例肾移植患者,按随机数字表法分为MMF组（n=13）和EC-MPS组（n=13）,两组患者分别于术后第1天给予MMF（750 mg q12 h）或EC-MPS（720 mg q12 h）、他克莫司、甲泼尼龙预防排斥反应。于术后第7天的早上服药前及服药后0.5,1,1.5,2,3,4,6,8,10,12 h采集静脉血样3 mL,采用UPLC-UV分析方法测定霉酚酸（MPA）血浆浓度。以 DAS 2.0药动学软件进行药动学分析,所有与剂量相关的两组药动学参数分别进行了剂量校正（C_max/D,C₀/D,AUC_{0-12 h}/D及AUMC_{0-12 h}/D）。用SPSS 17.0软件进行统计学分析。结果：术后第7天MMF和EC-MPS的主要药动学参数t_max分别为（1.54±0.9）h和（2.19±1.56）h（P> 0.05）;C_max/D分别为（5.12±2.83）mg·L^-1·g^-1和（9.51±7.38）mg·L^-1·g^-1（P> 0.05）;AUC_{0-12 h}/D分别为（19.13±7.78）mg·h·L^-1·g^-1和（25.96±11.78）mg·h·L^-1·g^-1（P> 0.05）。两组患者的药-时曲线个体间差异均较大,大部分患者观察到有双峰现象,极个别患者观察到有多峰。MMF组和EC-MPS组患者的MPA-AUC_{0-12 h}低暴露组比例分别为84.6%和46.15%,目标暴露组比例分别为15.4%和46.15%,仅有1例EC-MPS组患者为高暴露组。结论：MMF和EC-MPS在早期肾移植患者体内的药动学个体差异较大,需要常规监测MPA-AUC_{0-12 h},同时可结合C₀作为参考,以指导临床调整用药剂量。MMF和EC-MPS常规剂量下的MPA-AUC_{0-12 h}在早期肾移植患者中偏低,建议增加给药剂量。     

CYP3A基因多态性与心脏移植术后环孢素肾毒性的相关性

目的：探讨心脏移植受者CYP3A基因多态性与环孢素（CsA）所致肾毒性易感性的关系。方法：应用飞行时间质谱技术分析66例CsA免疫抑制治疗发生肾毒性（20例）和未发生肾毒性（46例）心脏移植术后患者的CYP3A基因多态性,并通过统计学分析CYP3A各单核苷酸多态性（SNP）位点基因型与CsA所致肾毒性之间的关系。结果：筛选出8个标签位点的等位基因在肾毒性和非肾毒性组间的分布差异均无统计学意义。经非条件性二元Logistic回归分析,在AIC定义的共显性和显性遗传模型下,未发现CYP3A基因8个SNP位点与CsA肾毒性的发生有显著性关联。结论：本研究显示心脏移植受者本次调查的CYP3A基因位点与CsA所致肾毒性无显著性关联。     

Induction antibody therapy in renal transplantation using early steroid withdrawal: long-term results comparing anti-IL2 receptor and anti-thymocyte globulin

Background

The present study intends to investigate the effects of anti-IL2 receptors (anti-IL2R) vs. lymphocyte-depleting agents in the early steroid withdrawal (ESW) scheme.

Methods

This is a retrospective cohort of 167 consecutive adult renal transplant recipients. Immunosuppression was based on tacrolimus and mycophenolate mofetil. Antibody induction therapy was carried out with lymphocyte-depleting agent (thymoglobulin) or anti-IL2R (Basiliximab or Daclizumab). ESW protocol was performed by administering intravenous methlyprednisolone as follows: 500 mg on day 0, 250 mg on day 1, 125 mg on day 2, 60 mg on day 3, and then stopped.

Results

Among the 167 studied patients, 79 (47.3%) received anti-IL2R and 88 (52.7%) received thymoglobulin induction. Significantly fewer episodes of acute rejection were seen at one year in patients treated with thymoglobulin as compared to anti-IL2R (25.6% vs. 11.4%, p = 0.01). At five years, a significant difference in graft survival was observed in anti-IL2R-treated patients compared with thymoglobulin (83.5% vs. 95.5%, p = 0.01). Multivariate analysis disclosed that female sex, antibody induction therapy using thymoglobulin and a trough tacrolimus level higher than 10 were protective factors against acute rejection, while there was a trend to increased risk of acute rejection at first year post-transplantation in patients presenting delayed graft function (DGF). Antibody induction was independently associated with patient and graft survival at five years (OR 0.213, 95% CI 0.046–0.991, p = 0.04).

Conclusion

ESW scheme seems to be safe and its use is beneficial since there are fewer adverse effects. Thymoglobulin induction therapy is associated with fewer rejection episodes. Induction therapy with thymoglobulin is associated with higher patient and allograft survival when comparing with anti-IL2R.     

肾移植患者应用咪唑立宾与麦考酚酸酯2种三联免疫抑制方案的疗效比较

目的:观察咪唑立宾(MZR)的免疫抑制效果及安全性,采用MZR替代麦考酚酸酯(MMF),比较环孢素A(CsA)+MZR/MMF+泼尼松龙(Pre)两种三联免疫抑制治疗的疗效。方法:尸体肾移植患者70例,按手术顺序交替登记MZR组和MMF组。移植后采用CsA+MZR/MMF+Pre三联免疫抑制疗法,MZR组剂量为200mg.d-1(体重>60kg)或150mg.d-1(体重<60kg);MMF组剂量为1500mg.d-1(体重>60kg)或1000mg.d-1(体重<60kg)。观察肾移植术后1年的人/肾存活率、急性排斥反应发生率及治疗逆转率、感染发生情况及药物毒副作用。结果:全部病例术后随访至少1年,MZR组和MMF组的急性排斥反应发生率分别为17.1%和11.4%,两组之间无显著性差异。MZR组和MMF组肺部感染的发生率分别为8.6%和48.6%,MMF组的发生率显著升高。血尿酸升高的发生率两组之间比较未见显著性差异,MZR组在术后24,36,48周时血尿酸的水平要高于MMF组。MZR组的持续用药率显著高于MMF组。结论:MZR可以与钙调神经素阻滞剂、激素联合应用于肾移植患者,具有一定的安全性和有效性,不良...     

长期存活肾移植患者环孢素血药浓度监测的临床研究

目的　分析长期存活肾移植患者环孢素 A( Cs A)血浓度监测的临床意义。 方法 　采用荧光偏振免疫法 ( FPIA)测定 674例肾移植患者5 3 93例次 Cs A血药浓度 ,根据术后时间分为正常组、中毒组、排异组 ,分析其疗效 ;并对其术后时间、年龄、药物相互作用、存活情况等进行统计分析。 结果 　中毒组、排异组与正常组相比 ,Cs A全血药浓度有显著性差异 ( P<0 .0 1) ;在同一时间段内 Cs A血药浓度随着年龄的增长呈下降趋势 ,术后时间 1年以上 ,3组患者的 Cs A血药浓度范围重叠较大。 结论 　根据 Cs A血药浓度监测结果及时调整给药方案 ,实行个体化给药方案 ,合理用药 ,建立长期随访制度 ,及时发现和处理并发症 ,是提高长期存活率的根本保证之一     

心脏移植术后患者环孢素血药浓度与不良反应分析

目的了解心脏移植术后患者环孢素（CsA）血药浓度变化和排斥反应、不良反应发生情况,并探讨其相关性。方法收集2010年1月至2011年12月在北京安贞医院行心脏移植术患者的病历资料进行回顾性分析,记录患者的一般情况、CsA血药浓度监测情况以及排斥反应和不良反应发生情况,分析CsA全血谷浓度（C0）和峰浓度（C2）与排斥反应和不良反应的关系。结果纳入分析的27例患者中男性24例,女性3例,平均年龄 （38±14）岁,平均身高 （170±10） cm,平均体重 （68.0±15.8） kg。原发疾病：扩张性心脏病18例,冠状动脉粥样硬化性心脏病4例,瓣膜性心肌病3例,心律失常性右心室心肌病1例,心肌致密化不全1例。术后早期（〈1个月）CsA血药浓度较低, 75例次C0检测中35例次（46.7%）、69例次C2检测中56例次（81.2%）低于有效浓度。C0在术后1~3个月升高, 4个月后逐渐降低,7个月后逐渐趋于稳定。C2在术后1~3个月升高,4个月后逐渐降低,13个月后略有回升。27例患者中有9例（33.3%）发生排斥反应,8例为急性排斥反应,发生在术后4~12个月,主要表现为乏力、食欲不振、活动后心悸、烦躁,其中1例死亡;1例为慢性排斥反应,发生在术后13个月,表现为心率增快和外周血淋巴细胞计数升高。27例中有7例（25.9%）出现肾功能损伤,发生在术后1个月内、3～6个月和7～12个月者分别为3、2、2例,主要表现为肌酐清除率下降,血清尿素、肌酐、钾升高和高尿酸血症;1例（3.7%）在术后2个月出现肝功能损伤,主要表现为丙氨酸转氨酶（ALT）和总胆红素（TBil）升高;18例（66.7%）出现总胆固醇 （TC）、低密度脂蛋白胆固醇 （LDL-C） 和三酰甘油 （TG） 升高,发生在术后3个月内和7~12个月者分别为17和1例;10例（37.0%）出现空腹血糖升高,发生在术后1个月内、4~12个月和18个月者分别为7、2和1例。未出现急性排斥反应者CsA的C0及C2均明显高于出现急性排斥反应者［（216±90） μg/L比（167±103） μg/L,（718±297） ng/ml比（472±251） μg/L,均P〈0.01］。出现不良反应者C0及C2均明显高于未出现不良反应者［（241±93） μg/L比（190±95） μg/L,（837±314） μg/L比（596±283） μg/L,均P＜0.01］。CsA的C0与血清尿素、肌酐和空腹血糖相关（r=0.359,P=0.000;r=0.170, P=0.014; r=0.164, P=0.018）,C0与C2均与TBil、TC和LDL-C相关（r=0.182, P=0.009; r=-0.170, P=0.018; r=0.267, P=0.001; r=0.320, P=0.000; r=0.251, P=0.001; r=0.275, P=0.000）。结论心脏移植术后患者CsA血药浓度与排斥反应和不良反应的发生密切相关,进行CsA血药浓度监测有利于及时调整CsA剂量,降低排斥反应和不良反应发生率。     

环孢素A与他克莫司应用于肝移植受者的药物经济学评价

目的评价环孢素A胶囊与他克莫司胶囊治疗肝移植受体排斥的经济性。方法选择在我院接受肝移植,并于2010年1月-2011年12月在门诊继续治疗的患者共60例,比较用药半年后的临床疗效、不良反应及用药成本,运用药物经济学的最小成本分析法对两种药物的经济效果进行评价。结果环孢素A胶囊组总有效率为78%,他克莫司胶囊组为86%,两组比较差异无统计学意义(P>0.05),环孢素A胶囊组的不良反应发生率较他克莫司胶囊组低。成本/效果比(C/E):环孢素A胶囊组为55.81,他克莫司胶囊组为46.19。结论与环孢素A胶囊比较,他克莫司胶囊用于肝移植受者更为经济有效。     

Nonlinear relationship between enteric-coated mycophenolate sodium dose and mycophenolic acid exposure in Han kidney transplantation recipients

The aim of the research was to investigate the pharmacokinetics (PK) of enteric-coated mycophenolate sodium (EC-MPS) by quantification of the active metabolite of mycophenolic acid (MPA) after multiple escalating oral doses in Han kidney transplant recipients. A total of 28 Han postoperative kidney transplant recipients were given a multiple-dose of 540, 720 or 900 mg of EC-MPS two times a day in combination with tacrolimus for 6 days. Blood specimens were collected at each time point from 0 to 12 h after EC-MPS administration. MPA plasma concentrations were measured by UPLCUV. The relationship between the EC-MPS dose and its PK parameters was assessed. In the range from 540 to 900 mg, C_max and AUC_012h did not increase with dose escalation. The AUC_012h, C_max, C₀ and T_max for the 540 720 and 900 mg doses were not significantly different, respectively (P >0.05). AUC_012 h and C_max were increased less than proportionally with increasing EC-MPS dose levels. Inter-individual variability in AUC_012h, C_max and C₀ were considerable. Nonlinear PK relationships were found from the doses of 540–900 mg of EC-MPS.     

Association of MDR1, CYP3A4*18B, and CYP3A5*3 polymorphisms with cyclosporine pharmacokinetics in Chinese renal transplant recipients

Objective  The objective of this study was to retrospectively evaluate the effects of MDR1, CYP3A4*18B, and CYP3A5*3 genetic polymorphisms on cyclosporine A (CsA) pharmacokinetics in Chinese renal transplant patients during the first month after transplantation. Methods  A total of 103 renal transplant recipients receiving CsA were genotyped for MDR1 (C1236T, G2677T/A, and C3435T), CYP3A4*18B, and CYP3A5*3. The predose and 2-h postdose concentrations of CsA (C₀ and C₂, respectively) were determined by fluorescence polarization immunoassay, and their relationships with corresponding genotypes and haplotypes were investigated. Results  Patients with a CYP3A4*1/*1 genotype were found to have a higher dose-adjusted concentration compared with those with CYP3A4*18B/*18B, as follows: for C₂, 19.3% (P = 0.008) during days 8-15, 35.2% (P = 0.008) during days 16–30, and for C₀, 39.7% (P = 0.012) during days 16–30. The dose-adjusted C₀ was higher in patients with MDR1 1236CC compared with those with 1236TT in the first month postoperation. The dose-adjusted C₀ in patients with the CYP3A5*3/*3 genotype was 25.5% and 30.7% higher than those with the wild-type genotype during days 8–15 (P = 0.011) and days 16–30 (P = 0.015), respectively. Haplotype analysis revealed that the dose-adjusted C₀ was higher in the first month following surgery in carriers of haplotype MDR1 CAC than in noncarriers. Polymorphisms of MDR1 and CYP3A5*3 did not affect dose-adjusted C_2. Conclusion  The data suggests that the CYP3A4*18B genotype affects CsA pharmacokinetics during the first month following surgery in Chinese renal transplant recipients. Patients with CYP3A4*18B alleles may require higher doses of CsA to reach the target levels. Large prospective studies may be needed to further explore the impact of MDR1 and CYP3A5*3 polymorphisms on CsA pharmacokinetics in renal transplant recipients.