肾移植受者术后并发泌尿系统恶性肿瘤(附12例报告)

目的分析肾移植受者术后并发泌尿系统恶性肿瘤的特点。方法回顾性分析1978年6月至2006年8月间3150例肾移植受者的临床资料，研究受者肾移植术后泌尿系统恶性肿瘤的发生率、发病年龄、发生时间以及免疫抑制剂的应用情况和肿瘤的治疗方案等。结果在3150例肾移植受者中，肾移植术后共发生33例（发生率1．05％）恶性肿瘤，其中泌尿系统恶性肿瘤12例（发生率0．38％），占肾移植术后恶性肿瘤的36．4％。这12例患者的发病年龄为48-66岁，平均（58．3±4．6）岁；肾移植术后发生肿瘤的平均时间为（62±18）个月；肾移植术后免疫抑制剂方案为：6例服用环孢素A＋硫唑嘌呤＋泼尼松，5例服用环孢素A＋霉酚酸酯＋泼尼松，1例服用他克莫司＋霉酚酸酯＋泼尼松。肿瘤发生后，12例患者中有11例施行了肿瘤根治性手术，其中1例在根治术后不久因突发脑溢血死亡。结论泌尿系统恶性肿瘤是肾移植受者术后的一个重要并发症；免疫抑制剂的使用与肿瘤的发生密切相关。因此，应定期评估肾移植受者术后的免疫状态，早期发现肿瘤，及时手术治疗，并适当减少免疫抑制剂用量。     

肾移植后并发恶性肿瘤五例报告

我院从１９７８年８月至１９９４年４月共作同种肾移植４７７例（５３０次）。术后发生恶性肿瘤５例，包括大脑网状细胞肉瘤１例，膀胱移行上皮癌２例，宿主肾透明细胞癌１例面部皮肤鳞癌１例。发生肿瘤时间分别为移植后４个月、２年、２年半，４年和１０年。经手术治疗，并将免疫抑制剂用量减少３０％，４例在诊断肿瘤后２年内死亡，１例术后至今（半年）仍健在。认为肾移植后并发恶性肿瘤与长期应用免疫抑制剂密切相应，发生肿瘤后     

肾移植术后近期并发痛风原因分析与防护

本文统计６３４例肾移植术后２年内发生痛风３４例，术后均使用大量速尿及环孢素Ａ。作者结合文献，阐述了环孢素Ａ、大剂量利尿剂、移植肾排斥反应等因素对肾移植术后并发痛风的影响，同时结合临床实践，提出了相应的预防及护理措施，强调消除诱发因素、碱化尿液、减少环孢素Ａ用量及正确应用速尿、肾功能临测、对症处理以及药物治疗的管理等在肾移植术后并发痛风患者防护中的重要意义。     

肾移植术后恶性肿瘤五例报告

本院１９８９年１０月至１９９６年７月接受同种异体肾移植术患者１９８例，５例并发恶性肿瘤，其中男３例，女２例，年龄５０～６７岁，平均６１．２岁。移植肾功能良好。使用环孢素Ａ（ＣｓＡ）、硫唑嘌呤（Ａｚａ）和泼尼松（Ｐｒｅｄ）免疫抑制治疗。术后１个月免疫抑...     

肾移植术后发生恶性肿瘤的探讨

1992～1996年我院行异体肾移植763例,术后发生恶性肿瘤7例,其中尿路肿瘤5例(膀胱肿瘤4例),本文就其病因学、临床治疗等进行探讨。认为肾移植术后大量免疫抑制药物的应用,尤其是环孢素A(CsA)的应用,使“免疫监护系统”受到破坏,导致肿瘤的发生,提出减少免疫抑制剂用量,将CsA的用量减少至原量的1/4,彻底清除病灶的治疗原则。     

肾移植术后并发肿瘤三例

肾移植术后并发肿瘤三例郝平和宋力唐迎九张斌例１，女性，２８岁。１９９２年４月接受同种尸体肾移植，术后应用环孢素Ａ（ＣｓＡ）、硫唑嘌呤（Ａｚａ）１００ｍｇｄ－１、泼尼松（Ｐｒｅｄ）１０ｍｇｄ－１免疫抑制治疗。２年后发现左颈部有一肿物随吞咽活动，诊断为甲...     

连续性肾脏替代治疗对肾移植患者血液环孢素A浓度的影响

为观察肾脏替代治疗对血环孢素Ａ（ＣｓＡ）的浓度有无影响，我们对２例肾移植术后行替代治疗患者的血及滤液中ＣｓＡ浓度进行了监测。２例患者肾移植术后出现肾功能不全，行连续性静脉－静脉血液滤过（ＣＶＶＨ）治疗。１例患者为肾移植术后急性排斥，尿量５９０ｍｌ／ｄ...     

肾移植术后并发泌尿系统恶性肿瘤44例临床分析

目的：对肾移植受者并发泌尿系统恶性肿瘤的情况进行分析，探讨其防治措施。方法：回顾分析肾移植术后发生泌尿系统恶性肿瘤的44例患者的临床资料。44例受者的免疫抑制方案，11例为环孢素A（CsA）、霉酚酸酯及泼尼松（Pred）联用，1例采用CsA、咪唑立宾及Pred联用，1例采用他克莫司、咪唑立宾及Pred联用，其余采用CsA、硫唑嘌呤及Pred联用。结果：44例的肿瘤诊断时间为移植后2～273个月，中位数为39．5个月，其中肾细胞癌5例，双侧肾盂输尿管癌10例，单侧肾盂输尿管癌16例，输尿管癌1例，膀胱癌12例；共有8例出现淋巴结或远处转移。诊断肿瘤后，对免疫抑制方案进行调整，43例患者接受了手术治疗，1例由于诊断不及时，丧失手术机会。经过治疗，39例存活，5例死亡。结论：肾移植术后恶性肿瘤尤其是泌尿系统恶性肿瘤的发生率明显升高，治疗的关键在于早期诊断、及时手术，并辅以免疫抑制方案的调整。     

肾移植术后恶性肿瘤的临床分析

目的总结并分析肾移植患者并发恶性肿瘤的临床特点,探讨其诊治方法。方法回顾性分析1998年至2003年间肾移植患者中发生恶性肿瘤的病例。结果在1293例肾移植患者中,29例发生恶性肿瘤,发病率2.24%(29/1293)。其中泌尿系统肿瘤23例(包括移植肾肾癌1例),胃癌、直肠癌各2例,肝细胞癌、胰腺癌各1例。23例患者行手术治疗,术后15例肿瘤复发。结论肾移植术后恶性肿瘤发病率明显升高,其中泌尿系统肿瘤居多;对移植后出现肿瘤类型的不同可采用不同的治疗方法。     

用硫氮唑酮减少肾移植受者环孢素A用量的临床观察

将钙拮抗剂硫氮唑酮（ｄｉｌｔｉａｚｅｍ，Ｄｉｌ）用于２６例服用环孢素Ａ（ＣｓＡ）的肾移植受者，以同期２１例受者为对照。术后第２、３、６、１２个月Ｄｉｌ组ＣｓＡ剂量分别较对照组少１２．５％、１３．４％，１８．３％及２９．０％，Ｐ均＜０．００１，而ＣｓＡ血浓度均较对照组高，ｐ＜０．０５。术后１年中Ｄｉｌ组ＣｓＡ用量每例平均较对照组少１４８７０ｍｇ。两组的急性排斥反应、肝功能损害发生率、血肌酐水平无显著性差异。Ｄｉｌ对减少肾移植受者对昂贵的ＣｓＡ用量效果显著，使用安全。     

尸体肾移植术后应用他克莫司的体会

目的：观察肾移植患者应用他克莫司（FK506）进行免疫抑制治疗的效果和副作用。方法：对肾移植术后应用FK506的64例患者的临床资料进行回顾性分析。结果：肾移植术后应用FK506,霉酚酸酯（MMF）及泼尼松的24例患者,术后未发生急性排斥反应;先用环孢素A,后因肝功能异常,急性排斥反应及慢性排斥反应而改用FK506的40例患者,大部分排斥缓解,肝功能改善;FK506的主要副作用有血糖升高（10．9％）和肾毒性（4．7％）,结论：FK506是一种强效的免疫抑制剂,其用量的个体差异很大。     

Malignant tumors after renal transplantation

Abstract: The rate of certain malignancies in renal transplant recipients is 14 to 500 times higher than the rate in the general population. The reported prevalence rates for malignant tumors in various kidney recipient series range from 4% to 18% with an average of 6%. The tumors occur in patients who are younger than individuals affected in the general population, and the incidence rates rise with each year after transplantation. Since 1975, we have recorded 52 cases of malignancy development in 50 (3.7%) patients who were treated with P + AZA, P + CsA + AZA, or P + CsA + MMF therapy (P, prednisolone; AZA, azathioprine; CsA, cyclosporin A; MMF, mycophenolate mofetil). In this article, 50 renal transplant recipients who developed malignancy and were followed by the Transplantation Center at Ba?kent University Faculty of Medicine were analyzed. Analysis revealed that patients who received CsA had a higher incidence of Kaposi's sarcoma than those who received the standard regimen. Regarding other tumor types, our results showed no statistical differences among the incidence rates in the different treatment groups.     

肾移植术后早期主动减少免疫抑制剂用量的前瞻性研究

目的探讨对肾移植术后受者早期主动减少免疫抑制剂用量的临床必要性和安全性。方法随机选择63例尸体肾移植受者为观察组,58例尸体肾移植受者为对照组,两组受者均采用环孢素(CsA)+麦考酚吗乙酯(MMF)+泼尼松三联免疫抑制方案。于术后第6周对观察组63例受者予以主动减少免疫抑制剂用量(将CsA血药谷浓度维持在200～250 ng/ml,MMF按受者体质量主动减药),术后4～6个月开始按个体状况将MMF用量调至减药前水平。对照组按常规免疫抑制方案治疗。观察两组受者术后6周至1年的血清肌酐(Scr)、血尿素氮(BUN)、CsA血药谷浓度、肺部感染发生率、急性排斥反应(AR)发生率。结果随访1年期间,观察组受者Scr、BUN基本稳定在同一水平,且与对照组比较差异无统计学意义(均为P>0.05)。观察组与对照组的AR发生率分别为8%与9%,比较差异无统计学意义(P>0.05)。两组的肺部感染率分别为8%(5/63)和14%(8/58),比较差异有统计学意义(P<0.05),对照组有2例发展为严重的肺部感染。结论肾移植术后早期主动减少免疫抑制剂用量能有效降低此阶段肺部感染发生率,且AR发生率并没有增加。     

Sequential antilymphoblast globulin and cyclosporine for renal transplantation

The nephrotoxic effects of cyclosporine (CsA) seem to be augmented by co-existing renal injury. A high rate of prolonged delayed function (acute tubular necrosis [ATN]) and non-function (NF) has been associated with the use of CsA prior to and following renal transplantation. Cyclosporine has also been associated with a slower recovery of allograft function and poor baseline renal function even in allografts that function immediately compared with conventionally treated recipients. In 1983 we hypothesized that the rate of ATN and NF following renal transplantation could be decreased and more normal kidney function achieved if renal injury was resolved before adding the nephrotoxic effects of CsA. A group of 300 nonsplenectomized, uremic recipients have received 304 renal transplants and have been initially immunosuppressed with azathioprine, prednisone, and Minnesota antilymphoblast globulin (ALG) prior to starting maintenance CsA and prednisone. The incidence of NF has been 1.9% and the development of ATN has been 7.6% following transplantation with sequential use of ALG and CsA. Other benefits to the renal recipient have also occurred with use of this immunotherapy protocol. Renal allograft survival for recipients of first, second, and third renal allografts has been higher than that generally reported with cyclosporine and prednisone alone. Rejection episodes have been infrequent during the first six months posttransplant, as 75% and 62% of first and second renal allograft recipients have remained rejection-free. Clinically significant infectious complications were infrequent. No cadaver recipient has developed a lymphoma. Moreover, the initial hospitalization following transplantation with sequential ALG/CsA has been short and generally uncomplicated. We conclude that sequential ALG/CsA following renal transplantation provides excellent early posttransplant immunosuppression while avoiding the nephrotoxic effects of CsA and also provides the steroid and infection-sparing benefits derived from maintenance CsA therapy.     

肾移植术后环孢素向硫唑嘌呤转换的临床研究

目的 观察肾移植木后环孢素向硫唑嘌呤转换的临床效果。方法 选择60例术后1年以上、肾功能稳定的肾移植受者进行免疫抑制剂从环孢素向唷唑嘌呤的转换。结果 60例病人平均血清肌酐在转换后1个月明显下降(148±58.5至132±86.9mmol/L,P<0.01),并在以后几年内继续下降,转换后6年时平均血清肌酐为112±39.8mmol/L。转换后平均血压也明显下降,并且抗高血压药物数量逐渐减少(P<0.01)。分别有9例(15％)和3例(6.7％)病人在转换后3个月内和3个月后发生急性排斥反应。转换后1年、5年人/肾存活率分别为95％/81.7％、86.7％/78.3％。5例(8.7％)病人因药物副作用和慢性排斥反应从硫唑嘌呤再转换为环孢素。结论 肾移植受者在术后一定时间将免疫抑制剂从环孢素转换为硫唑嘌呤是一种安全的免疫抑制方案,具有较好的移植肾长期存活。     

The effect of antilymphocyte serum, fractionated donor bone marrow, and cyclosporine on renal allograft survival in mongrel dogs.

The effect of combined treatment with antilymphocyte serum, fractionated donor bone marrow, and a limited course of cyclosporine on renal allograft survival in mongrel dogs was examined. Recipients were treated with ALS from day -5 to day +7, relative to transplantation on day 0 with an MLR-mismatched donor. Fractionated donor bone marrow cells (BMFr3) obtained by density gradient separation were infused 3-7 days after ALS treatment. CsA treatments were begun either 3-7 days after ALS plus BMFr3 infusion or 3-7 days after treatments with ALS alone. Extended allograft survival was achieved at all CsA doses in BMFr3-infused, ALS-treated recipients. Allografts were sustained throughout the CsA treatment period without rejection in the majority of recipients (6 of 8) receiving ALS plus BMFr3 and CsA at 20 Mg/kg/day for 60 days. By contrast, few grafts were sustained through 30 days of treatment with CsA at 3.2 (1 of 12) or 10 mg/kg/day (2 of 9) in ALS plus BMFr3-treated recipients. Cyclosporine treatment was ineffective at all doses in augmenting allograft prolongation in ALS-treated recipients that did not receive BMFr3. Nearly all (6 of 7) long-term survivors (greater than 180 days) were BMFr3-treated. Peripheral blood lymphocytes or bone marrow cells of these long-term survivors proliferated normally in response to Con A and PWM, and were MLR responsive to third-party cells but did not have reduced MLR responsiveness to donor alloantigen in all cases. These long-term survivors promptly rejected third-party renal allografts without adverse effects on the original transplant's function. These results show that long-term renal allograft survival with specific unresponsiveness to the donor can result from the combined treatment with ALS plus donor BMFr3 and a limited course of CsA.     

骁悉与小剂量环孢素A在尸体肾移植中的联合应用

为观察骁悉（ＭＭＦ）与小剂量环孢素Ａ（ＣｓＡ）联合应用于尸体肾移植中的效果，将１６例患者随机分为３组，ＭＭＦ２．０ｇ组（ＭＭＦ用量为２．０ｇ／ｄ）；ＭＭＦ１．５ｇ组（ＭＭＦ用量为１．５ｇ／ｄ）；硫唑嘌呤（Ａｚａ）组。３组患者均同时接受相似剂量的ＣｓＡ和类固醇治疗。结果ＭＭＦ２．０ｇ组未发生急性排斥；ＭＭＦ１．５ｇ组１例（１／５）患者先后发生２次排斥；Ａｚａ组３例（３／５）患者各发生１次排斥。术后６个月ＭＭＦ２．０ｇ组患者血清肌酐值明显低于Ａｚａ组，其所用的ＣｓＡ剂量低于Ａｚａ组。认为ＭＭＦ无明显肝、肾毒性，每天２．０ｇ口服，并与小剂量ＣｓＡ和类固醇联合应用，临床疗效明显优于传统的三联疗法。     

Use of sphingosine-1-phosphate 1 receptor agonist, KRP-203, in combination with a subtherapeutic dose of cyclosporine A for rat renal transplantation

BACKGROUND: We demonstrate the long-term effectiveness of KRP-203 treatment in combination with a subtherapeutic dose of cyclosporine A (CsA) on rat renal allografts. METHODS: We tested the effect of KRP-203 in combination with CsA using a rat skin allograft model. The Pharmacokinetic interaction between CsA and KRP-203 was evaluated. The selectivity of KRP-203 for sphingosine-1-phosphate (S1P)1 and S1P3 receptors were investigated in vitro. Heart rate alteration following bolus injection of phosphorylated KRP-203 (KRP-203-P) or FTY720 (FTY720-P) was also monitored in rats. Finally, the long-term effectiveness of KRP-203 in conjunction with a low dose of CsA was investigated in a rat renal transplantation model. RESULTS: Administration of KRP-203 with CsA prolonged skin allograft survival. KRP-203 and CsA had no effect on the pharmacokinetics of the other. While FTY720-P activated both S1P1 and S1P3 receptors, KRP-203-P selectively activated S1P1, but not the S1P3 receptor (EC50:>1000 nM). Compared to FTY720-P, a tenfold higher dose of KRP-203-P was necessary to induce transient bradycardia. With a low dose of CsA (1 mg/kg/day), KRP-203 (0.3 mg/kg/day) significantly prolonged renal allograft survival (P<0.05, survival time: 9.8 days (CsA) vs. >27.4 days (CsA+KRP)). Although a higher dose of CsA (3 mg/kg/day) alone kept recipients alive, this caused severe renal graft dysfunction. Use of KRP-203 (3 mg/kg/day) in conjunction with CsA markedly improved graft function (P<0.05, creatinine clearance: 0.41+/-0.25 ml/min [CsA] vs. 1.15+/-0.16 ml/min [CsA+KRP]). CONCLUSIONS: The selectivity of KRP-203 for S1P1 reduces the risk of bradycardia, and the combination therapy of KRP-203 with CsA represents a safe and effective strategy for use in renal transplantation.     

西罗莫司在肝移植术后肾功能异常患者中的应用

目的 探讨西罗莫司替换钙调磷酸酶抑制剂治疗肝移植术后肾功能不全的安全性和有效性.方法 北将肝移植术后发生肾功能不全的62例患者随机分为对照组和转换组.对照组29例,继续采用Tac(或CsA)、MMF及Pred的方案,血Tac(或CsA)浓度调整在治疗窗范围的下限;转换组33例,用SRL替换原方案中的Tac(或CsA),SRL的起始用量为2 mg/d,以后根据血SRL浓度及不良反应作相应调整,Tac(或CsA)减少至原用量的1/3～1/2,3 d后停用,MMF和Pred的用法不变.转换治疗后,对患者的肝肾功能、急性排斥反应及存活率进行随访监测,并观察患者在转换治疗期间发生的不良反应.结果 共有49例患者痊愈或者好转,13例死亡,对照组死亡8例,转换组死亡5例.随访9～51个月,转换组存活患者肝功能稳定,均未发生急性排斥反应.两组存活患者肾功能恢复后均未再出现反复,且转换组患者肾功能恢复时间明显缩短,治疗效果较好.转换组存活患者未发生严重不良反应,与对照组肺部感染发生率的比较,差异无统计学意义(P>0.05).结论 肝移植术后并发肾功能不全时,采用西罗莫司替换原免疫抑制方案中的CNI治疗是安全有效的.     

尼卡地平对肾移植受者环孢素A血浓度的影响

目的：研究尼卡地平对肾移植受者血压和环孢素A（CaA)全血谷值浓度的影响。方法：试验组62例肾移植术后肾功能恢复正常的受者服用尼卡地平，服药前后作自身对照；23例受者服用硝苯地平作为对照组，以CsA全血谷值浓度、CsA剂量、肌酐、血压作为临床评价指标。结果：试验组受者服用尼卡地平后CsA血药浓度显著升高、血压下降并维持在正常范围，与服用尼卡地平前比较，差异均有显著性意义（P＜0．01），6个月后环孢素剂量A减少达34．2％，对血肌酐无明显影响。结论：尼卡地平用于肾移植术后能有效治疗和预防高血压，并可提高CsA血药浓度，减少CsA用量和费用，并不增加CsA的毒性反应。尼卡地平与CsA合用可节省费用。