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。     

肾移植术后应用2种不同剂量环孢素A的临床对照研究

目的:探讨肾移植术后应用环孢素A(CsA)、强的松(Pred)和吗替麦考酚酯(MMF)后是否允许CsA减量而不增加排斥反应发生率,是否可以减少CsA相关副作用以提高疗效。方法:将使用常规剂量CsA的肾移植患者(213例)与使用低剂量CsA患者(176例)进行对照研究。结果:2组肾功能水平、排斥反应发生率及人/肾存活率均无显著性差异,但低剂量CsA组总体疗效稍好,而且不良反应发生率明显减少。结论:肾移植术后患者CsA+MMF+Pred三联用药,在使用足够剂量MMF的情况下,可以允许CsA减量而不增加急性排斥反应的风险。     

Milnacipran for fibromyalgia: a useful addition to the treatment armamentarium

Kidney transplantation is the best treatment option in chronic kidney disease patients. Despite the new potent immunosuppressants, the long-term graft survival has not significantly improved. This is a rather complex issue with interrelationship between pretransplant donor–recipient variables, recipient post-transplant perioperative non/immunological factors, the combination/dose of maintenance immunosuppression and the general noncompliance of the patient. The recipients with an increased immunological risk should be maintained on triple therapy with steroids, preferably tacrolimus (Tac) or cyclosporine (CsA) plus mycophenolate mofetil (MMF). Eventual calcineurin inhibitor (CNI) minimization should be coupled with either protocol biopsies or frequent biochemistry monitoring including periodical assessment of anti-human leukocyte antigen and donor-specific antibodies. Recipients with standard immunological risks may be considered for as low as possible triple immunosuppression (steroids, Tac/CsA, MMF) after a period of 6 – 12 months. In cases of CNI minimization, a modification with a higher dose of the other two drugs in the triple therapy combination might be considered. The nonadherence to the prescribed maintenance therapy should be regularly checked-up. In conclusion, antibody induction, MMF, steroids and low-dose Tac/CsA should be the mainstream therapy in majority of patients. The short- and mid-term encouraging results for CNI minimization/withdrawal seem to correspond to recent findings of chronic antibody-mediated rejection, and long-term results need further evaluation.     

The use of mycophenolate mofetil in transplant recipients

With the development of new immunosuppressive agents, the focus of anti-rejection therapy has shifted from prevention of acute allograft rejection to an emphasis on sufficient immunosuppression with minimal toxicity. Mycophenolate mofetil (MMF) is a recently developed immunosuppressive drug, which acts to inhibit T and B cell proliferation by blocking the production of guanosine nucleotides required for DNA synthesis. It also prevents the glycosylation of adhesion molecules that are involved in attachment of lymphocytes to endothelium and potentially in leukocyte infiltration of an allograft during an immune response. High-quality randomized clinical trials have demonstrated that MMF, when used with cyclosporine (CsA) and steroids, reduces the frequency and severity of acute rejection episodes in kidney and heart transplants, improves patient and graft survival in heart allograft recipients and increases renal allograft survival at 3 years. It has also been effective in reversing acute and resistant rejection episodes in heart, kidney and liver recipients. The ability of MMF to facilitate sparing of other immunosuppressive agents, particularly in CsA-related nephrotoxicity, is also promising. By permitting reduction in CsA doses, MMF may stabilize or improve renal graft function in patients with CsA-related nephrotoxicity or chronic allograft nephropathy. Early results of phase I and II trials evaluating MMF therapy in liver and combined pancreas/kidney transplant recipients are encouraging. The main adverse effects associated with oral or intravenous MMF are gastrointestinal and hematologic in nature. Although the direct costs of using MMF vs. azathioprine (AZA) are higher, the decreased incidence and treatment of acute rejection in patients treated with MMF supports its use as a cost-effective option during the first year following transplantation.Thus, MMF has become an important therapeutic tool in the transplant clinician's armamentarium. Ongoing issues to be resolved in clinical trials include the role of MMF in the absence of other potent agents, e.g., as monotherapy or with a steroid but without calcineurin inhibitor; whether MMF will have an impact on chronic allograft dysfunction; and the cost-effectiveness of treatment following the first year of transplantation.     

高龄患者肾移植126例临床分析

目的 :探讨高龄患者肾移植的临床特点及四联免疫抑制疗法对临床治疗效果的影响。方法 :分析 1990年 1月至 2 0 0 0年 12月 12 5 1例肾移植中 12 6例高龄患者临床资料 ,将术后使用免疫抑制剂为三联疗法 (CsA +Aza +激素 )的 5 5例作组Ⅰ ;而使用四联疗法 (CsA +MMF +激素 +抗T细胞单抗 )的 71例作为组Ⅱ ,组Ⅱ中 4 7例患者术后使用 2周Wu -T3抗排斥治疗 ,另 2 4例应用抗IL- 2R抗体预防急性排斥反应。将两组的术后并发症、急性排斥率及 1年人 /肾存活率相比较 ,并与本院同期非高龄患者相同指标比较。结果 :高龄患者肾移植后心脑血管并发症以及感染发生率均明显高于非高龄患者。组Ⅰ和组Ⅱ患者的术后并发症发生率分别为 74 5 5 %和 38 0 3% ;急性排斥发生率分别为 12 73%和 4 2 3% ;1年人 /肾存活率分别为 81 82 % /78 18%和 97 18% /95 77%。结论 :高龄患者肾移植术后较容易发生心脑血管并发症及感染 ,使用新的四联免疫抑制疗法能有效地降低心脑血管并发症、感染和急性排斥反应的发生率 ,1年人 /肾存活率亦明显提高。     

霉酚酸酯在肾移植术后的临床应用

目的:建立霉酚酸酯(MMF)与环孢素A(CsA)及皮质激素(Pred)合用时CsA的治疗窗,分析霉酚酸酯在肾移植术后的临床疗效.方法:对临床164份病例资料进行回顾性分析.结呆:MMF方案CsA的治疗窗为:1mo内为150～300ng/ml,1～3mo 120～260ng/ml,3～6mo 110～225ng/ml;MMF方案中毒反应、排异反应发生均低于经典三联方案(CsA 硫唑嘌呤Aza Pred).结论:MMF方案优于经典三联方案,可安全、有效地预防肾移植术后急慢性排斥及中毒反应的发生率.     

巴利昔单抗对肾移植受者白细胞介素2和可溶性白介素2受体的影响

目的:分析巴利昔单抗和抗CD3单克隆抗体(OKT3)对肾移植受者白细胞介素2(IL2)和可溶性白细胞介素2受体(sIL2R)的影响,评价其治疗的有效性及安全性。方法:将74例肾移植受者随机分为巴利昔单抗组(n=39)和OKT3组(n=35)。所有病人均采用环孢素+霉酚酸酯+泼尼松三联免疫抑制维持治疗。巴利昔单抗组:分别于术前2h和术后d4使用巴利昔单抗20mg,静脉滴注;OKT3组:从术后d1开始,给OKT35mg静脉滴注,qd,共7～10d。检测术后2mo内IL2和sIL2R浓度,观察急性排斥反应(AR)、肌酐恢复时间、不良反应、受者和移植肾存活情况。结果:巴利昔单抗组IL2和sIL2R浓度明显低于OKT3组(P<0.05)。有12例病人发生AR,巴利昔单抗组3例,OKT3组9例(P<0.05)。巴利昔单抗组肌酐恢复时间(4.7±s2.1)d,明显短于OKT3组(9±5)d(P<0.05)。巴利昔单抗组感染7例,细胞因子释放综合征0例,过敏反应0例,明显低于OKT3组(P<0.05)。结论:巴利昔单抗明显降低IL2和sIL2R浓度和AR发生率,不良反应少,是一种强效安全的免疫抑制剂。     

达利珠单抗在预防同种肾移植急性排斥反应中的临床应用(英文)

目的 :探讨达利珠单抗在预防同种肾异体移植术后急性排斥反应的作用。方法 :回顾分析了已随访 1a的 2 8例 (男性 2 4例 ,女性 4例 ,年龄 32a±s 5a)应用 2剂达利珠单抗的病人的临床效果 ,并以同期肾移植 80例 (男性 6 8例 ,女性 12例 ,年龄34a± 11a)作为对照组。所有病人均给予以麦考酚酸酯 (mycophenolatemofetil,MMF) ,环孢素 (ci closporin ,CsA) ,甲基强的松龙 (methylprednisolone ,MPD)和泼尼松 (prednisone ,Pred)为基础的免疫抑制方案 ;达利珠单抗在基础治疗方案上 ,分别于手术前 2 4h内和手术后d 14按照剂量为 1mg·kg- 1通过静脉注射给药。观察急性排斥反应发生率、药物不良反应、感染发生率、病人和移植物的 1a存活率。所有病人均随访 1a以上。结果 :达利珠单抗组在 3mo内急性排斥反应发生率 (4% )显著低于对照组 (2 5 % ) ,差异有显著意义 (P <0 .0 5 ) ;达利珠单抗具有良好的耐受性 ,无细胞因子释放综合征的发生 ;在感染及不良反应方面与对照组比较无显著性差异 ;2组比较病人 1a的存活率 (达利珠单抗组为 89% ,对照组为 96 % )和移植肾存活率 (达利珠单抗组 89% ,对照组 94 % )无显著性差异 (P >0 .0 5 )。结论 :2剂达利珠单抗加上MMF ,CsA ,MPD ,Pred联合应用的免疫抑制方案对预防同种异     

巴利昔单抗联合鼠抗人CD3单克隆抗体在高致敏受者肾移植中的临床应用

目的:探讨巴利昔单抗与鼠抗人CD3单克隆抗体(OKT3)联合诱导在高致敏受者肾移植临床应用中的有效性及安全性。方法:术前2个月内群体反应性抗体(PRA)检测值均>50%的尸体供肾肾移植受者20例,其中9例受者接受巴利昔单抗联合OKT3免疫诱导(联合诱导组),11例受者接受OKT3常规免疫诱导(OKT3诱导组),均以他克莫司(Tac)+吗替麦考酚酯(MMF)+泼尼松(Pred)为基础免疫抑制方案,评估术后移植肾功能恢复情况、3个月内急性排斥反应发生率、1年内肺部感染发生率、1年人/肾存活率及移植肾功能。结果:联合诱导组、OKT3诱导组肾移植术后3个月内急性排斥反应发生率及术后1年内肺部感染发生率分别为11.1%vs.36.4%(P=0.319),11.1%vs.63.6%(P=0.028);联合诱导组患者术后1周内移植肾功能恢复正常比例明显高于OKT3诱导组(88.9%vs.27.3%,P=0.010);联合诱导组术后1年人/肾存活率均为100%,与OKT3诱导组(分别为90.9%、81.8%)比较,差异不显著(P=1.00和P=0.100);术后1年联合诱导组、OKT3诱导组血肌酐值分别为(105±24)、(97±22)μmol·L-1(P=0.437)。结论:巴利昔单抗联合OKT3进行免疫诱导,在预防高致敏受者术后早期排斥反应的同时,缩短了移植肾功能的恢复时间,是一种安全、有效的防治策略。     

Basiliximab: a review of its use as induction therapy in renal transplantation

Basiliximab (Simulect), a chimeric (human/murine) monoclonal antibody, is indicated for the prevention of acute organ rejection in adult and paediatric renal transplant recipients in combination with other immunosuppressive agents.Basiliximab significantly reduced acute rejection compared with placebo in renal transplant recipients receiving dual- (cyclosporin microemulsion and corticosteroids) or triple-immunotherapy (azathioprine- or mycophenolate mofetil-based); graft and patient survival rates at 12 months were similar. Significantly more basiliximab than placebo recipients were free from the combined endpoint of death, graft loss or acute rejection 3 years, but not 5 years, after transplantation.The incidence of adverse events was similar in basiliximab and placebo recipients, with no increase in the incidence of infection, including cytomegalovirus (CMV) infection. Malignancies or post-transplant lymphoproliferative disorders after treatment with basiliximab were rare, with a similar incidence to that seen with placebo at 12 months or 5 years post-transplantation. Rare cases of hypersensitivity reactions to basiliximab have been reported.The efficacy of basiliximab was similar to that of equine antithymocyte globulin (ATG) and daclizumab, and similar to or greater than that of muromonab CD3. Basiliximab was as effective as rabbit antithymocyte globulin (RATG) in patients at relatively low risk of acute rejection, but less effective in high-risk patients. Numerically or significantly fewer patients receiving basiliximab experienced adverse events considered to be related to the study drug than ATG or RATG recipients. The incidence of infection, including CMV infection, was similar with basiliximab and ATG or RATG.Basiliximab plus baseline immunosuppression resulted in no significant differences in acute rejection rates compared with baseline immunosuppression with or without ATG or antilymphocyte globulin in retrospective analyses conducted for small numbers of paediatric patients. Limited data from paediatric renal transplant recipients suggest a similar tolerability profile to that in adults. Basiliximab appears to allow the withdrawal of corticosteroids or the use of corticosteroid-free or calcineurin inhibitor-sparing regimens in renal transplant recipients.Basiliximab did not increase the overall costs of therapy in pharmacoeconomic studies.CONCLUSION: Basiliximab reduces acute rejection without increasing the incidence of adverse events, including infection and malignancy, in renal transplant recipients when combined with standard dual- or triple-immunotherapy. The overall incidence of death, graft loss or acute rejection was significantly reduced at 3 years; there was no significant difference for this endpoint 5 years after transplantation. Malignancy was not increased at 5 years. The overall efficacy, tolerability, ease of administration and cost effectiveness of basiliximab make it an attractive option for the prophylaxis of acute renal transplant rejection.     

Trough levels of mycophenolic acid and its glucuronidated metabolite in renal transplant recipients

OBJECTIVE: The prophylactic use of the immunosuppressant prodrug, mycophenolate mofetil (MMF) to prevent graft rejection in renal transplant patients is continuing to increase. We measured trough levels of the active metabolite, mycophenolic acid (MPA) and its inactive glucuronide (MPAG) in renal recipients with the aim of characterizing individual variability and of ascertaining factors influencing trough levels, in particular the effect of differences in renal function and the effect of drugs given concurrently. METHODS: Laboratory and clinical data obtained in 35 renal recipients treated with triple therapy (MMF, cyclosporin A (CsA), steroids) were included in this retrospective study. Trough levels of MPA and MPAG were obtained after transplantation and up to 16 months post transplantation where the mean observation period was 5.7 months. Plasma levels were measured using a validated HPLC assay. RESULTS: A total of 212 plasma concentrations of MPA and 209 of MPAG were measured. There was considerable intra- and interindividual variability in MPA and MPAG trough levels especially in the early post-transplantation phase. At a fixed dose of 2 g/d MMF, the mean MPA level during the first 30 days averaged 1.46 +/- 1.31 microg/ml vs. 1.87 +/- 0.89 microg/ml after 30 days and later (p = 0.130) and the mean MPAG concentration averaged 188.1 = 142.8 [microg/ml vs. 98.09 +/- 52.4 microlg/ml (p 0.003). The MPAG levels were positively correlated with the serum creatinine concentrations (r = 0.815, p < 0.001), and in the case of MPA there was a correlation with the serum protein concentrations (r = 0.258, p = 0.001). Concomitant drug treatment using CsA, steroids and furosemide were without effect of the measured plasma concentrations, but in the case of xipamide (+) and diltiazem (-) an effect on MPA and MPAG levels and a co-effect depending on the serum creatinine could not be excluded. Neither CsA trough levels nor hemoglobin levels were related to MPA and MPAG trough levels. CONCLUSIONS: The data of this study demonstrate that there is substantial individual variability in the trough levels of MPA and MPAG after renal transplantation which may be associated with the functional status of the graft and the serum protein level. Whether comedication with xipamide and diltiazem affects the plasma levels of MPA and MPAG remains to be clarified in further investigations.     

肾移植后应用霉酚酸酯与硫唑嘌呤的疗效比较

目的:比较肾移植受者应用霉酚酸酯(MMF)与硫唑嘌呤(Aza)的临床疗效.方法:肾移植术后患者86例随机分为MMF组,即用环孢素(CsA)加MMF、泼尼松(Pred)三联用药方案者40例;Aza组为CsA加Aza、Pred三联用药方案者46例;定期监测其肝肾功能、CsA全血浓度等,观察时间为1 a.结果:两组患者术后肾功能恢复情况基本相同,但MMF组患者血肌酐(Cr)值显著低于Aza组,差异有显著性,;MMF组的CsA用量及其血药浓度也显著低于Aza组;MMF对急慢性排斥反应效果较Aza好;两组患者消化道反应、白细胞减少、感染等并发症的发生率差异无显著性,Aza组药物性肝损害发生率高于MMF组.结论:含MMF的三联用药更有利于移植肾功能的恢复和降低肝肾毒性发生率.     

霉酚酸酯替代硫唑嘌呤在肾移植中的应用

目的 观察霉酚酸酯(MMF)替代硫唑嘌呤(Aza)在预防肾移植术后急性排斥中的作用。方法 回顾性分析我院95例肾移植后应用皮质激素(Perd)，环孢素(CsA)，MMF(或)硫唑嘌呤(Aza)三联免疫抑制剂治疗，其中分成MMF组57例，Aza组38例，MMF组适当减少环孢素用量。结果 MMF组发生急性排斥率为8．89%(5／57)，Aza组为23．7%(9／38)。结论 以MMF代替Aza应用于肾移植术后，可以减少术后急性排斥及CsA的用量，减少药物的肝肾毒性。     

普乐可复在肝脏移植术后的免疫治疗与监测

目的：观察肝脏移植术后应用普乐可复（FK506）免疫治疗的临床效果。方法：回顾性分析我院69例患者肝脏移植术后使用以FK506为基础的三联免疫治疗方案的临床资料，即FK506＋霉酚酸酯（MMF）＋皮质激素。结果：69例中发生急性排斥反应8例（11．6％），经调整药物剂量后逆转。FK506的副作用主要有精神及神经系统紊乱（20．3％）、高血压（11．6％）、血糖升高（20．3％）及肝肾功能异常（8.7％）等。结论：FK506是一种安全、强效的免疫抑制药物，用药剂量应根据药物谷值浓度及个体差异进行调整。     

5­year follow-up of a randomized clinical study comparing everolimus plus reduced-dose cyclosporine with mycophenolate mofetil plus standard-dose cyclosporine in de novo kidney transplantation: Retrospective single center assessment

The aim of this study is to evaluate the efficacy and safety of everolimus plus reduced­dose cyclosporine compared with mycophenolate mofetil plus standard­dose cyclosporine 5 years after living donor kidney transplantation.Between March 2008 and August 2009, 24 living donor kidney transplantations were enrolled in a 2-year, multicenter, randomized phase 3 study (RAD001A1202 study). 24 recipients were randomly classified into two groups and closely observed for 5 years. 13 recipients were administered steroid, reduced­dose cyclosporine, everolimus and basiliximab (EVR group). 11 recipients were administered steroid, standard-dose cyclosporine, mycophenolate mofetil and basiliximab (STD group). Two groups were compared not only in graft function including estimated glomerular filtration rate (eGFR), and proteinuria, but also in adverse events such as de novo donor-specific antibody (DSA) production, rejection, new­onset diabetes, hyperlipidemia, and cytomegalovirus (CMV) infection.No graft loss was identified in 5 years. The incidences of acute T cell rejection, de novo DSA production, hyperlipidemia, and new­onset diabetes were similar. eGFR levels throughout the observation periods were similar. Three cases of proteinuria were identified in STD group. One case of proteinuria observed in EVR group was well controlled with angiotensin receptor blocker. Incidence of CMV infection in CMV antibody­positive recipients was significantly lower in EVR group.The safety and efficacy of reduced­dose cyclosporine and everolimus protocol were similar to those of standard­dose cyclosporine and mycophenolate mofetil other than for superior prevention of CMV infection.     

巴利昔单抗在预防肾移植后排斥反应中的应用

目的:探讨巴利昔单抗诱导治疗预防肾移植后急性排斥反应的有效性和安全性。方法:在使用环孢素、霉酚酸酯及激素三联抗排斥的基础上,将42例肾移植受者随机分2组,每组各21例,试验组术前30min及术后d4各给予巴利昔单抗20mg+氯化钠注射液100mL,静脉滴注,对照组只使用氯化钠注射液静脉滴注。评价急性排斥反应的发生率、严重程度以及巴利昔单抗治疗的安全性。结果:试验组急性排斥反应发生率10%(2/21),发生时间(2.8±s0.8)mo;对照组发生率29%(6/21),发生时间(1.1±0.7)mo,早于试验组(P<0.01)且严重程度高于试验组。血肌酐恢复正常的时间试验组(4.0±0.7)d,对照组(7.8±1.6)d,P<0.01。不良反应发生率2组间差异无显著意义,P<0.05。结论:巴利昔单抗联合环孢素、霉酚酸酯和激素预防肾移植后急性排斥反应安全有效。     

肾移植病人应用霉酚酸酯与硫唑嘌呤的临床疗效比较

目的：比较霉酚酸酯（MMF）、硫唑嘌呤（Aza）在肾移植病人中的临床效果。方法：肾移植术后服用霉酚酸酯、硫唑嘌呤患者各28例，均采用同服环孢菌素和泼尼松三联用药方案，每月常规监测环孢菌素A（CsA）全血浓度、血常规、肾功能、肝功能、尿常规。结果：MMF组的CsA用量及其血药浓度显著低于Aza组（P〈0．05），MMF组患者血肌酐（Cr）值也显著低于Aza组（P〈0．05），同时MMF组对急慢性排斥反应效果较Aza组好，药物性肝损害发生率低于Aza组。结论：MMF较Aza不良反应小，减少或避免肝、肾功肾功能损害的发生机会，使肾移植的成功率明显提高。     

肾移植术后西罗莫司的应用方案选择

本综述总结西罗莫司用于预防肾移植术后排斥反应的各种用药方案,从急性排斥发生率、肾功能、人/肾存活率4个方面综合比较各种用药方案同其他传统免疫抑制方案的优劣。综合比较显示,肾移植术后转换使用西罗莫司是最值得推荐的用药方案。在环孢素与西罗莫司联用（CsA＋SRL）过程中减、停环孢素也是可以考虑的方案,但要注意控制西罗莫司浓度。西罗莫司可以替换麦考酚酸酯,此时钙调神经蛋白抑制剂（CNI）应适当减量。起始低剂量西罗莫司与CNI联用（CNI＋SRL）,以及起始足量CNI＋SRL并维持、起始不含CNI以及术后移植肾功能延迟恢复（DGF）过渡期使用西罗莫司均应当避免。西罗莫司支持术后撤停激素,此种情况下推荐西罗莫司与他克莫司联用。需定期监测西罗莫司谷浓度,并多数情形下推荐使用首剂负荷剂量。     

肾移植术后早期应用雷帕霉素的疗效和并发症观察

目的:评价肾移植术后早期应用雷帕霉素(RPM)的疗效和安全性。方法:58例同种尸体供肾移植患者分为试验组(28例)与对照组(30例),免疫抑制方案分别为环孢素A(CsA)+RPM+强的松(Pred)、CsA+霉酚酸酯(MMF)+Pred。观察2组在移植术后6月内的疗效、并发症及药品不良反应情况,同时监测血脂水平、肝肾功能等生化指标,分析2种免疫抑制方案对移植肾急性排斥反应、人/肾存活率的影响。结果:2组患者观察期内均移植肾带功存活。试验组急性排斥反应发生率(4/28,14.3%)稍低于对照组(5/30,16.7%),差异无统计学意义。试验组发生血脂异常11例(39.3%),切口感染4例(14.3%),腹泻3例(10.7%),白细胞减少1例(3.6%);对照组中血脂异常3例(10.0%),切口感染2例(6.7%),腹泻8例(26.7%),白细胞减少5例(16.7%)。结论:肾移植术后早期应用CsA+RPM+Pred三联免疫抑制治疗方案,会产生更强的免疫抑制效果,术后急性排斥反应发生率稍低于对照组。其主要副作用是血脂升高和切口感染,但腹泻和白细胞减少的发生率明显低于对照组。     

肾移植患者神经钙蛋白阻滞药的肾毒性

目的:了解减少或停用神经钙蛋白阻滞药能否改善肾移植后慢性移植物肾病患者的肾功能.方法:1999年1月～2001年5月期间,对病理诊断为慢性移植物肾病(Ⅰ级)肾功不全的93例肾移植患者随机分为A、B两组,A组(50例):在1～2周内将其神经钙蛋白阻滞药(环孢素或他克莫司)减少至原剂量的三分之一或完全停用,同时适当增加硫唑嘌呤或霉酚酸脂的用量;B组(43例):环孢素A或他克莫司未作大幅度减量、而是仅适当增加硫唑嘌呤或霉酚酸脂的用量.对两组患者进行至少3年的随访,比较其移植肾功能、观察两组急性排斥反应有无差异等.结果:3年后A组有31例(62.0%)患者移植肾功能得以好转或不再继续恶化,而B组除4例(9.3%)移植肾功能维持在原有水平外,其他患者肾功能均进行性恶化;3年后A组肾功能明显好于B组;B组3年后尿蛋白定量明显增多,而A组无明显改变;两组急性排斥反应发生率无显著差异.结论:大幅度减少甚至停用神经钙蛋白阻滞药可使部分肾移植后慢性移植物肾病患者的肾功能得以改善或者阻止其进行性恶化.这种药物调整是安全的.