肾移植后不同免疫抑制方案的效果及不良反应的临床分析

目的 总结肾移植后使用不同免疫抑制方案的效果和不良反应,以提高人/肾的长期存活率.方法 对单中心3102例肾移植受者的临床资料进行回顾性分析,所采用的免疫抑制方案有环孢素A(CsA)+硫唑嘌呤(Aza)+泼尼松(Pred)、低剂量CsA+吗替麦考酚酯(MMF)+Pred、低剂量他克莫司(Tac)+MMF+Pred、低剂量CsA(或Tac)+西罗莫司(SRL)+Pred等方案,分析各方案的效果和不良反应.结果 低剂量CsA+MMF+Pred方案的人/肾1、5、10年存活率均高于CsA+Aza+Pred方案,而高血压、震颤、高尿酸、肝肾毒性、白细胞下降等的发生率显著低于CsA+Aza+Pred方案(P＜0.05),腹泻发生率显著高于CsA+Aza+Pred方案(P＜0.05).低剂量Tac+MMF+Pred方案的高血糖发生率显著高于低剂量CsA+MMF+Pred方案(P＜0.05),多毛症发生率显著低于低剂量CsA+MMF+Pred方案(P＜0.05);低剂量CsA(或Tac)+SRL+Pred方案的腹泻、高尿酸血症、肝肾毒性和多毛症等的发生率显著低于低剂量CsA(或Tac)+MMF+Pred方案(P＜0.05),但高血脂发生率显著高于后者(P＜0.05).以低剂量Tac为基础的方案者高血糖发生率显著应用低剂量CsA者.结论 低剂量CsA(或Tac)+MMF+Pred方案改善了肾移植受者和移植肾的存活,降低了不良反应发生率,尤以低剂量Tac+MMF+Pred方案为优;调整免疫抑制方案或剂量,改善饮食习惯,加强锻炼,优化降血压、降血脂、控制血糖的治疗措施对预防和控制不良反应尤为重要.

Abstract：

Objective To summarize the incidence and treatment experience of the effectiveness and adverse reactions of the different immunosuppressive protocols and to increase the long-term survival rate in kidney recipients. Methods Single-center retrospective analysis was performed on 3102 cases of kidney transplant recipients in effectiveness and adverse reactions of different immunosuppressive protocols. The immunosuppressive protocols were as follows: CsA + Aza + Pred,low dose CsA + MMF + Pred, low dose Tac + MMF + Pred, low dose CsA + SRL + Pred, and low dose Tac+ SRL+ Pred. Results The 1-, 5-, 10-year survival rate of patients/kidney in low dose CsA + MMF + Pred protocol was higher than that in CsA + Aza + Pred protocol. The incidence of adverse reactions, such as hypertension, hyperuricemia, kidney and liver toxicity, and leukopenia was significantly lower, but the incidence of diarrhea was significantly higher in CsA + MMF + Pred protocol than in CsA + Aza + Pred protocol (all P＜0. 01). The incidence of hyperglycemia was significantly higher (P＜0. 05), and that of hairy and gingival hyperplsia was significantly lower (P＜0. 05) in low dose Tac+ MMF+ Pred than in low dose CsA+ MMF+ Pred protocol. The incidence of hyperlipidemia in low dose CsA (or Tac)+ SRL + Pred was significantly higher than in CsA (or Tac)+ MMF+ Pred protocol (P＜0. 05). The incidence of hirsutism in low dose Tac + SRL + Pred was significantly lower than that in CsA + SRL + Pred protocol (P ＜ 0. 05). The incidence of hyperglycemia in low dose Tac + SRL + Pred was significantly higher than that in low dose CsA + SRL + Pred protocol. Conclusion The triple drug protocol with a low dose of CsA (or Tac)+ MMF+ Pred significantly improved the survival of renal transplant recipients and graft, and reduced the incidence of adverse reactions, especially Tae + MMF + Pred protocol. Adjustment of the immunosuppressant dosage and protocol, improvement of eating habits, exercise, reduction of blood pressure, reduction of blood lipid, and control of blood glucose were particularly important in preventing and controlling adverse reactions during kidney transplantation.     

肾移植后早期应用咪唑立宾的有效性及安全性

目的 探讨肾移植后早期应用咪唑立宾( MZR)的有效性和安全性.方法 采用前瞻性临床随机对照研究.将61例首次肾移植受者按随机数字表法分为2组:(1)MZR组:33例,应用他克莫司(Tac)+ MZR+泼尼松(Pred)预防排斥反应;(2)吗替麦考酚酯组(MMF)组:28例,应用Tac+ MMF+ Pred预防排斥反应.MZR的用法为:体重＜50 kg者为150mg/d,早餐后口服;体重≥50kg者为200 mg/d,分早、晚2次口服.MMF、Tac和Pred按常规剂量服用.2组受者均于术前2h和术后4d接受巴利昔单抗(20mg/d)诱导治疗.观察并比较2组受者术后6个月内的急性排斥反应(AR)发生率、移植肾存活率以及高尿酸血症、骨髓抑制、巨细胞病毒感染、胃肠道反应等的发生率.结果 术后6个月内,MZR组AR发生率为15.2％,MMF组AR发生率为10.7％ (P＞0.05);MZR组移植肾存活率为97.0％,MMF组移植肾存活率为89.3％(P＞0.05).MZR组和MMF组间高尿酸血症、骨髓抑制、胃肠道反应和肺部感染的发生率的差异无统计学意义(P＞0.05).其中,MZR组未发生巨细胞病毒感染,而MMF组则发生4例(36.4％),差异有统计学意义(P＜0.05).结论 在严密监测下,MZR可应用于肾移植术后早期抗排斥反应治疗.     

环孢素A转换为他克莫司对慢性移植肾肾病患者的治疗效果

目的 探讨由环孢素A(CsA)转换为他克莫司(Tac)为主的免疫抑制方案对慢性移植肾肾病(CAN)患者的治疗效果.方法 选择接受同种肾移植后发生CAN的患者153例,患者肾移植后均采用CsA、吗替麦考酚酯(MMF)及泼尼松(Pred)的免疫抑制方案.根据是否以Tac替换CsA将患者分为两组.(1)CsA组:45例,进入研究后患者维持原免疫抑制方案.(2)Tac组:108例,进入研究后将CsA转换为Tac,停用CsA后立即开始服用Tac,MMF和Pred的用法同CsA组.对所有患者随访12个月,观察人/移植肾存活率、急性排斥反应发生率、移植肾功能、24 h尿蛋白定量、移植肾穿刺病理学活检及免疫抑制剂的不良反应等指标.结果 随访12个月时,CsA组和Tac组患者存活率均为100%,移植肾存活率分别为86.6%和93.5%(P＜0.05);急性排斥反应发生率分别为4.4%(2/45)和3.7%(4/108)(P＞0.05),6例发生急性排斥反应的患者均经甲泼尼龙冲击治疗3 d后逆转.Tac组患者移植肾功能明显改善,并且出现重度蛋白尿、重度肾间质纤维化和肾小管萎缩的患者比例较CsA组显著减少(P＜0.05).Tac组有13.8%(15例)的患者出现轻度血糖增高,发生率显著高于CsA组的4.4%(2例)(P＜0.05);Tac组有22.2%(24例)的患者发生高血压,发生率显著低于CsA组的55.6%(25例)(P＜0.05);17例因使用CsA而出现牙龈增生和多毛症者,经转换治疗后,症状均明显好转.结论 由CsA转换为Tac为主的免疫抑制方案能够显著改善CAN患者的移植肾功能,延缓CAN的发展,转换过程中未发生严重Tac不良反应并且改善了使用CsA时出现的不良反应.

Abstract：

Objective To investigate the effect of conversion from cyclosporine A (CsA) to tacrolimus (Tac) on chronic allograft nephropathy (CAN). Methods 153 CAN patients undergoing kidney transplantation received CsA, mycophenolate mofetil (MMF) and prednisone (CsA-MMF-Pred) regimen after kidney transplantation, and divided into 2 groups according to whether CsA were maintained in the immunosuppressive regimen: CsA + MMF + Pred group (CsA group, n = 45); Tac + MMF + Pred group (Tac group, n = 108). The patients were followed up with patient/kidney survival rate, acute rejection incidence, renal function, 24-h proteinuria and adverse events of immunosuppressive drugs for 12 months. Results Compared with CsA group, the transplanted kidney survival rate was significantly higher in Tac group (93. 5 % vs 86.6 %, P＜0. 05). Acute rejection (AR) was diagnosed in 4. 4 % (2/45) of recipients in CsA group and 3. 7 % (4/108) in Tac group (P＞0. 05) respectively. Acute rejection (2 cases in CsA group and 4 in Tac group) was reversed by 500 mg of methylprednisolone for consecutive 3 days, and the patients in Tac group showed a significantly lower degree of interstitial fibrosis and tubular atrophy (IF/TA) (P＜0. 05).Renal allograft functions and 24-h proteinuria during a follow-up period of 12 months were significantly improved in Tac group (P ＜ 0. 05). Incidence of mild hyperglycemia in Tac Group (13.8 %, 15/108) was significantly higher than in CsA group (4.4 %, 2/45), and that of hypertension in Tac group (22. 2 %, 24/108) was significantly lower than in CsA group (55.6 %,25/45). CsA-related side effects (such as hirsutism and gingival hypertrophy) in 17 patients were greatly improved after conversion from CsA to Tac treatment. Conclusion The conversion from CsA to Tac on the patients with CAN can improve renal allograft function, retard the progression of renal allograft dysfunction, reduce the incidence of CsA-related side effects and not generate serious adverse effects of Tac.     

肺移植100例临床分析

目的 探讨肺移植术后免疫抑制方案的安全性及有效性、术后并发症、死亡原因及其危险因素等.方法 回顾性分析100例肺移植受者的临床资料.100例受者中,单肺移植72例,双肺移植28例,61例在体外循环支持下完成,其中常规体外循环(CPB)5例,体外膜肺氧合(ECMO) 56例.2007年之前53例受者使用环孢素A(CsA)+吗替麦考酚酯(MMF)+皮质激素的三联免疫抑制方案预防排斥反应(CsA组),随后47例采用他克莫司(Tac)+ MMF+皮质激素的三联免疫抑制方案(Tac组),所有受者均使用了达利珠单抗或巴利昔单抗进行免疫诱导治疗.结果 受者术后1、2、3、5年累积存活率分别为73.3％、61.6％、53.5％和40.7％,CsA组受者存活时间为(36.57±3.44)个月,Tac组受者存活时间为(35.00±2.33)个月,两组比较,差异无统计学意义(P＞0.05).术后主要死亡原因包括原发性移植物功能丧失(PGD)、急性排斥反应(AR)、闭塞性细支气管炎(BOS)、感染等.CsA组AR和BOS的发生率明显高于Tac组(P＜0.05),但Tac组术后新发糖尿病的发生率显著高于CsA组(P＜0.05).等级相关分析显示,AR与BOS的发生呈正相关(相关系数=0.340,P＜0.01).单因素和多因素COX比例风险回归模型分析结果均显示,使用循环支持,原发病为特发性肺间质纤维化,术后出现AR、BOS和感染等因素会降低受者的存活时间(P＜0.05).结论 肺移植术后以CsA或Tac为主的免疫抑制方案均是有效的免疫抑制措施.术后加强随访、及时处理出现的并发症是延长受者存活时间和改善受者生存质量的关键.     

应用环孢素A的肾移植患者合用地尔硫的临床效果观察

目的探讨使用环孢素A(CsA)的肾移植患者合用地尔硫(艹卓)的临床效果.方法将1529例肾移植患者分为研究组和对照组,研究组肾移植术后应用CsA、硫唑嘌呤(Aza)及泼尼松(Pred)(研究组1)或CsA、霉酚酸酯(MMF)及Pred(研究组2)预防排斥反应,两个研究组同时加用地尔硫(艹卓);对照组使用CsA、Aza及Pred预防排斥反应,不用地尔硫(艹卓).观察研究组和对照组的CsA用量、血CsA浓度、移植效果、急性排斥反应发生率以及CsA的肝、肾毒性.结果研究组1的CsA用量低于对照组(P＜0.05),但血CsA浓度明显高于对照组(P＜0.01);研究组2的CsA用量显著低于对照组(P＜0.01),但血CsA浓度与对照组相近(P＞0.05);研究组1和研究组2移植肾功能恢复正常的时间分别缩短至4.7 d和3.9 d,较对照组显著提前(P＜0.05);两个研究组的急性排斥反应发生率较对照组明显降低(P＜0.05,P＜0.01).结论应用CsA的肾移植患者合用地尔硫(艹卓),能明显提高血CsA浓度,从而减少CsA用量,同时能促进移植肾功能的恢复,改善移植效果.     

两种免疫抑制方案在肾移植中应用的不良反应对比分析

目的 评价免疫抑制剂的不同组合在肾移植中应用的安全性。方法 回顾分析肾移植患者的临床资料，术后采用环孢素A(CsA)、硫唑嘌呤(Aza)及泼尼松(Pred)三联用药预防排斥反应者37例(Aza组)，采用CsA、霉酚酸酯(MMF)及Pred三联用药者35例(MMF组)。比较分析两个组用药后的药物不良反应。结果 在消化道反应、白细胞减少、全血细胞减少以及继发感染发生率等方面，MMF组与Aza组的差异无显著性(P＞0．05)，而肝功能损伤的发生率，Aza组明显高于MMF组(P＜0．05)。结论 在药物性肝损伤方面，以MMF、CsA及Pred组成的免疫抑制方案较CsA、Aza及Pred方案相对安全。     

肾移植后不同免疫抑制方案的效果及不良反应的临床分析

Objective To summarize the incidence and treatment experience of the effectiveness and adverse reactions of the different immunosuppressive protocols and to increase the long-term survival rate in kidney recipients. Methods Single-center retrospective analysis was performed on 3102 cases of kidney transplant recipients in effectiveness and adverse reactions of different immunosuppressive protocols. The immunosuppressive protocols were as follows: CsA + Aza + Pred,low dose CsA + MMF + Pred, low dose Tac + MMF + Pred, low dose CsA + SRL + Pred, and low dose Tac+ SRL+ Pred. Results The 1-, 5-, 10-year survival rate of patients/kidney in low dose CsA + MMF + Pred protocol was higher than that in CsA + Aza + Pred protocol. The incidence of adverse reactions, such as hypertension, hyperuricemia, kidney and liver toxicity, and leukopenia was significantly lower, but the incidence of diarrhea was significantly higher in CsA + MMF + Pred protocol than in CsA + Aza + Pred protocol (all P＜0. 01). The incidence of hyperglycemia was significantly higher (P＜0. 05), and that of hairy and gingival hyperplsia was significantly lower (P＜0. 05) in low dose Tac+ MMF+ Pred than in low dose CsA+ MMF+ Pred protocol. The incidence of hyperlipidemia in low dose CsA (or Tac)+ SRL + Pred was significantly higher than in CsA (or Tac)+ MMF+ Pred protocol (P＜0. 05). The incidence of hirsutism in low dose Tac + SRL + Pred was significantly lower than that in CsA + SRL + Pred protocol (P ＜ 0. 05). The incidence of hyperglycemia in low dose Tac + SRL + Pred was significantly higher than that in low dose CsA + SRL + Pred protocol. Conclusion The triple drug protocol with a low dose of CsA (or Tac)+ MMF+ Pred significantly improved the survival of renal transplant recipients and graft, and reduced the incidence of adverse reactions, especially Tae + MMF + Pred protocol. Adjustment of the immunosuppressant dosage and protocol, improvement of eating habits, exercise, reduction of blood pressure, reduction of blood lipid, and control of blood glucose were particularly important in preventing and controlling adverse reactions during kidney transplantation.     

肾移植后不同免疫抑制方案的效果及不良反应的临床分析

Objective To summarize the incidence and treatment experience of the effectiveness and adverse reactions of the different immunosuppressive protocols and to increase the long-term survival rate in kidney recipients. Methods Single-center retrospective analysis was performed on 3102 cases of kidney transplant recipients in effectiveness and adverse reactions of different immunosuppressive protocols. The immunosuppressive protocols were as follows: CsA + Aza + Pred,low dose CsA + MMF + Pred, low dose Tac + MMF + Pred, low dose CsA + SRL + Pred, and low dose Tac+ SRL+ Pred. Results The 1-, 5-, 10-year survival rate of patients/kidney in low dose CsA + MMF + Pred protocol was higher than that in CsA + Aza + Pred protocol. The incidence of adverse reactions, such as hypertension, hyperuricemia, kidney and liver toxicity, and leukopenia was significantly lower, but the incidence of diarrhea was significantly higher in CsA + MMF + Pred protocol than in CsA + Aza + Pred protocol (all P＜0. 01). The incidence of hyperglycemia was significantly higher (P＜0. 05), and that of hairy and gingival hyperplsia was significantly lower (P＜0. 05) in low dose Tac+ MMF+ Pred than in low dose CsA+ MMF+ Pred protocol. The incidence of hyperlipidemia in low dose CsA (or Tac)+ SRL + Pred was significantly higher than in CsA (or Tac)+ MMF+ Pred protocol (P＜0. 05). The incidence of hirsutism in low dose Tac + SRL + Pred was significantly lower than that in CsA + SRL + Pred protocol (P ＜ 0. 05). The incidence of hyperglycemia in low dose Tac + SRL + Pred was significantly higher than that in low dose CsA + SRL + Pred protocol. Conclusion The triple drug protocol with a low dose of CsA (or Tac)+ MMF+ Pred significantly improved the survival of renal transplant recipients and graft, and reduced the incidence of adverse reactions, especially Tae + MMF + Pred protocol. Adjustment of the immunosuppressant dosage and protocol, improvement of eating habits, exercise, reduction of blood pressure, reduction of blood lipid, and control of blood glucose were particularly important in preventing and controlling adverse reactions during kidney transplantation.     

肾移植后不同免疫抑制方案的效果及不良反应的临床分析

Objective To summarize the incidence and treatment experience of the effectiveness and adverse reactions of the different immunosuppressive protocols and to increase the long-term survival rate in kidney recipients. Methods Single-center retrospective analysis was performed on 3102 cases of kidney transplant recipients in effectiveness and adverse reactions of different immunosuppressive protocols. The immunosuppressive protocols were as follows: CsA + Aza + Pred,low dose CsA + MMF + Pred, low dose Tac + MMF + Pred, low dose CsA + SRL + Pred, and low dose Tac+ SRL+ Pred. Results The 1-, 5-, 10-year survival rate of patients/kidney in low dose CsA + MMF + Pred protocol was higher than that in CsA + Aza + Pred protocol. The incidence of adverse reactions, such as hypertension, hyperuricemia, kidney and liver toxicity, and leukopenia was significantly lower, but the incidence of diarrhea was significantly higher in CsA + MMF + Pred protocol than in CsA + Aza + Pred protocol (all P＜0. 01). The incidence of hyperglycemia was significantly higher (P＜0. 05), and that of hairy and gingival hyperplsia was significantly lower (P＜0. 05) in low dose Tac+ MMF+ Pred than in low dose CsA+ MMF+ Pred protocol. The incidence of hyperlipidemia in low dose CsA (or Tac)+ SRL + Pred was significantly higher than in CsA (or Tac)+ MMF+ Pred protocol (P＜0. 05). The incidence of hirsutism in low dose Tac + SRL + Pred was significantly lower than that in CsA + SRL + Pred protocol (P ＜ 0. 05). The incidence of hyperglycemia in low dose Tac + SRL + Pred was significantly higher than that in low dose CsA + SRL + Pred protocol. Conclusion The triple drug protocol with a low dose of CsA (or Tac)+ MMF+ Pred significantly improved the survival of renal transplant recipients and graft, and reduced the incidence of adverse reactions, especially Tae + MMF + Pred protocol. Adjustment of the immunosuppressant dosage and protocol, improvement of eating habits, exercise, reduction of blood pressure, reduction of blood lipid, and control of blood glucose were particularly important in preventing and controlling adverse reactions during kidney transplantation.     

环孢素A短期替代他克莫司对肾移植后新发糖尿病的改善作用

目的 初步探讨环孢素A(CsA)短期替代他克莫司(Tac)对移植后新发糖尿病( NODAT)的改善作用.方法 前瞻性分析19例以Tac为基础免疫抑制剂的NODAT患者的资料.其中7例NODAT诊断明确后将Tac转换为CsA,6个月后再次转换回Tac(转换组);12例诊断为NODAT后继续应用Tac(对照组).结果 转换组空腹血糖(FPG)由人组时的(8.3±3.9)mmol/L降至转换12个月时的(5.6±1.8)mmol/L(P＜0.01),对照组入组时和12个月时的FPG分别为(8.1±3.5) mmol/L和(8.0±3.0)mmol/L(P＞0.05),组间12个月时相比较,差异有统计学意义(P＜0.05).转换组糖化血红蛋白(HbA1c)由入组时的(6.8±0.8)％降至12个月时的(6.1±0.4)％(P＜0.05),对照组入组时和12个月时的HbA1c分别为(6.9±0.7)％和(6.8±1.5)％(P＞0.05),两组间12个月时相比较,差异有统计学意义(P＜0.05).随访结束时,转换组中4例(57.1％,4/7)NODAT完全缓解,而对照组中无NODAT缓解病例(P＜0.01).转换组血压和血脂水平在转换之后维持稳定.两组间移植物功能以及急性排斥反应发生率的差异无统计学意义(P＞0.05).两组随访结束时移植物和受者存活率均为100％.结论 发生NODAT的肾移植受者将Tac短期(6个月)转换为CsA,可明显改善糖代谢异常.     

肾移植术后代谢综合征发病率及其危险因素临床研究

目的 调查肾移植术后代谢综合征(MS)发病率,初步探讨肾移植术后代谢综合征发病机制.方法 前瞻性观察292例肾移植受者,纳入的观察对象在移植术后6个月内未曾发生急性排斥、钙调蛋白抑制剂(CNI)毒性反应和严重感染,术后6个月尿常规及肾功能正常,移植前终末期肾衰竭(ESRF)原发病为慢性肾小球肾炎,无糖尿病史.1年后进行血、尿生化及体格检查,并计算体重身高指数(BMI).随机抽取普通社区居民200例作为对照.结果 肾移植受者术后Ms发病率为25.7%,显著高于普通社区人群的15%.男性肾移植受者MS发病率高于女性受者.环孢素+骁悉+强的松治疗组MS发病率高于普乐可复+骁悉+强的松治疗组,但差异无显著意义.环孢素维持剂量>200mg/d的肾移植受者MS发病率显著高于环孢素剂量≤200mg/d的肾移植受者.普乐可复维持剂量>2mg/d的肾移植受者MS发病率显著高于普乐可复剂量≤2mg.d的肾移植受者.肾移植受者中超重和肥胖的发病率与普通社区居民无显著差异,超重和肥胖的肾移植受者与超重和肥胖的普通社区居民比较,其MS发病率也无显著差异.结论 本研究结果表明肾移植术后MS发病率显著增加,提示MS系慢性移植肾肾病(CAN)非免疫性危险因素;本研究结果还提示男性、环孢素维持剂量>200mg.d-1、普乐可复维持剂量>2mg.d-1是肾移植术后MS发病的危险因素,而超重和肥胖不是本研究中肾移植受者术后MS发病率增加的主要因素.     

Long-term renal transplant function in recipient of simultaneous kidney and pancreas transplant maintained with two prednisone-free maintenance immunosuppressive combinations: tacrolimus/mycophenolate mofetil versus tacrolimus/sirolimus

BACKGROUND: It is not known how different steroid-free immunosuppressive combinations affect long-term kidney transplant function in recipients of simultaneous kidney and pancreas transplant (SPK). Here, we sought to evaluate, in SPK recipients, the impact on long-term renal allograft function of two Tac-based prednisone-free maintenance immunosuppressive protocols: tacrolimus (Tac)/mycophonelate mofetil (MMF) versus Tac/ sirolimus (SRL). METHODS: In this single-center, retrospective, sequential study, we analyzed 59 SPK transplant patients with at median follow up of 5 years. All patients received induction therapy with thymoglobulin and maintenance immunosuppression with Tac/MMF (n=22) or Tac/SRL (n=37). There were no differences between the two groups in regards to age, gender, race, panel reactive antibodies, degree of mismatch, donor age, incidence of delay graft function, and Tac trough levels at different time points after transplantation. RESULTS: Kaplan-Meier patient survival at 6 years after transplantation was not statistically different between the two groups. Rate of ACR was similar. Kidney survival, even if not statistically significant, was better in the Tac/MMF group than in the Tac/SRL (90.7% vs. 70.7%, P=0.09). The slope of glomerular filtration rate decline per month at 5 years after transplantation was not statistically different between the two groups. Both groups had the same decline over time in glomerular filtration rate of 0.40+/-0.06 mL/min/1.73/month. Pancreas survival at 6 years after transplantation was 100% in both treatment groups. CONCLUSIONS: Our data suggest that, in SPK recipients, long-term kidney allograft survival and function are not statistically different. A trend toward an increased rate of renal allograft loss was found in the Tac/SRL-treated group.     

Polyomavirus BK infection in Greek renal transplant recipients

BK polyoma virus associated nephropathy is increasingly recognized as an important cause of allograft dysfunction among renal transplant recipients. Herein we present the cases of two renal transplant recipients who developed progressive functional deterioration suspicious for BK polyoma virus involvement. One patient had been treated with mycophenolate mofetil (MMF), cyclosporine (CsA), and prednisolone (P), and the second patient with tacrolimus (Tac), MMF, and (P). Using quantitative real-time polymerase chain reactions for BK virus DNA, we monitored the content of BK virus in the blood to evaluate disease progression. The high BK virus load initially detected in the blood samples from these patients decreased in the patient who received MMF, CsA, and P after the reduction of immunosuppression, but not in the patient who was treated with Tac, MMF and P. In contrast to previous reports, our patients had not received treatment with anti-lymphocyte globulin (ALG) or monoclonal anti-CD3 antibody (OKT3) after transplantation. It is concluded that even in the absence of vigorous antirejection treatment, immunosuppressive therapy based on Tac and MMF may carry the risk of BK virus-associated nephropathy. Because BK virus specific antiviral therapy is not available, its course may be monitored by measuring the viral load in blood.     

36-month follow-up of 75 renal allograft recipients treated with steroids, tacrolimus, and azathioprine or mycophenolate mofetil

OBJECTIVES: The aim of this retrospective study was to assess the incidence of acute rejection episodes (AR), diabetes mellitus (DM), and serum creatinine (SCr) among renal transplant recipients treated with tacrolimus (Tac), steroids (S), and mycophenolate mofetil (MMF) or azathioprine (Aza). METHODS: Seventy-five renal allograft recipients enrolled in the COSTAMP study were followed for a period of 3 years. Patients were randomized to receive either Tac and MMF (n = 41) or Tac and Aza (n = 34) concomitantly with steroids. Follow-up assessments were performed at 3, 6, 12, 24, and 36 months. RESULTS: Patient survival at month 36 was 91.18% in the Tac/Aza/S group and 97.56% in the Tac/MMF/S group. Graft survival at month 36 was 82.35% and 85.37%, respectively. During the study period, 22 cases of biopsy-proven AR were diagnosed in 17 patients (22.6%). After 36 months the total number of AR was 11 in the Aza-treated group (32.4%) and 11 in the MMF-treated group (26.8%). DM was diagnosed de novo in 17 individuals (22.6%). During 36 months, 10 patients from Aza-treated group (29.4%) and seven from MMF-treated group developed DM (17.1%). Serum creatinine values were not significantly different in both arms of the study. Comparison of arterial blood pressure and total cholesterol revealed no significant changes in any of the studied groups. CONCLUSIONS: We conclude that combinations of steroids, tacrolimus, and azathioprine or MMF provide good results with regard to renal function.     

Clinicopathological aspects of 18 Kaposi's sarcoma among 1055 Greek renal transplant recipients

The incidence of Kaposi's sarcoma (KS) in transplant recipients is 400-500 times greater than that in the general population, and is rising within the transplant population. In this study, between March 1983 and December 2001, 1055 cases were recorded where KS developed in 18 patients (1.7%) who were treated with AZA + CsA + MP, MMF + CsA + MP, MMF + Tac + MP, CsA + MP, or AZA + MP therapy (AZA, azathioprine; CsA, cyclosporine A; MP, methylprednisolone; MMF, mycophenolate mofetil; Tac, Tacrolimus). In the present study, 18 renal transplant recipients who developed KS and were followed and analyzed. Analysis revealed that a continuous state of immunodeficiency is important for the development of KS. Prognosis in patients with KS limited to the skin is favorable, while visceral involvement is associated with high mortality. Transplant function is well preserved in most of the cases. The association, previously described, between human herpesvirus 8 (HHV8) and transplant-associated KS also exists in the studied population.     

Tacrolimus versus cyclosporine after lung transplantation: a prospective, open, randomized two-center trial comparing two different immunosuppressive protocols.

BACKGROUND: The need for better immunosuppressive protocols after lung transplantation led us to investigate tacrolimus (Tac) in combination with mycophenolate mofetil (MMF) and steroids or cyclosporine (CsA) in combination with MMF and steroids in a prospective, open, randomized trial after lung transplantation. METHODS: Between September 1997 and April 1999, 50 lung transplant recipients were randomized to receive either Tac (n = 26) or CsA (n = 24) in combination with MMF and steroids. All patients underwent induction therapy with rabbit antithymocyte globulin (ATG) for 3 days. Freedom from acute rejection (AR), patient survival, infection episodes, and side effects were monitored. RESULTS: There was no difference in patient demographics between the two groups. Six-month and 1-year survival was similar (84.6% and 73.1% in the Tac group vs 83.3% and 79.2% in the CsA group). Freedom from AR at 6 months and 1 year after lung transplantation was slightly higher in the Tac group (57.7% and 50% vs 45.8% and 33.3%, p = not significant [n.s.]), whereas the number of treated rejection episodes per 100 patient days in the Tac group was significantly lower (0.225 vs 0.426, p < .05). Four patients in the CsA group had to be switched to Tac. Two patients in the CsA group had to be retransplanted. Incidence of infections was similar in both groups with a trend toward more fungal infections in the Tac group (n = 7 vs n = 1, p = n.s.). CONCLUSIONS: The combination of Tac and MMF seems to have slightly higher immunosuppressive potential compared with CsA and MMF. The effectiveness of Tac as a rescue agent is not paralleled with undue signs of overimmunosuppression.     

Metabolic Syndrome Components After Pediatric Liver Transplantation: Prevalence and the Impact of Obesity and Immunosuppression

Metabolic syndrome is associated with long‐term morbidity and mortality after adult liver transplantation (LT). Whether pediatric LT recipients have a higher prevalence of metabolic syndrome remains controversial. In a cross‐sectional study, we evaluated pediatric LT recipients aged 8–30 years using National Health and Nutrition Examination Survey (NHANES) protocols. LT recipients were matched by gender, race/ethnicity, and age with controls from NHANES. Pediatric LT recipients (n = 83), after adjusting for overweight/obesity and glucocorticoid use, had increased prevalence of prehypertension and hypertension, impaired glucose tolerance (IGT; 2‐h glucose after oral glucose tolerance test ≥140 mg/dL), and low high‐density lipoprotein compared to matched NHANES controls (n = 235) despite a lower prevalence of overweight/obesity. Among LT recipients, the adjusted odds of IGT doubled for every 7.5 years taking calcineurin inhibitors (odds ratio = 2.10, 95% confidence interval 1.06–4.17 per 7.5 years taking calcineurin inhibitors, p = 0.03). Among all subjects with IGT, LT recipients had a lower prevalence of overweight/obesity and less insulin resistance (homeostatic model assessment of insulin resistance) than did controls with IGT. Among normal weight subjects, LT recipients were significantly more likely than controls to have prehypertension/hypertension, IGT, low high‐density lipoprotein, and metabolic syndrome. Pediatric LT recipients have unique metabolic syndrome profiles and risk factors and will require tailored screening and management protocols.     

Blood pressure profile and treatment quality in liver allograft recipients-benefit of tacrolimus versus cyclosporine

Organ transplant recipients display a high cardiovascular mortality rate. The type of immunosuppression has a major impact on cardiovascular risk factors (e.g., hypertension [HTN]). We assessed 24-hour blood pressure (BP) and metabolic profiles in a cohort of 106 long-term liver allograft recipients treated with either tacrolimus (Tac) or cyclosporine (CyA). The median age of patients was 50.8 years (range, 11 to 77) and the median time of follow-up was 65.4 months (ranges 12 to 168). Immunosuppression included low-dose steroids and either Tac (n = 46) or CyA (n = 60). Twenty-four-hour BP measurements revealed a significant difference in systolic BP (127.1 mmHg [94 to 163] Tac versus 132.7 mmHg [103 to 177] CyA; P <.03), and in mean arterial and diastolic blood pressures. In addition, the relative number of normotensive patients was significantly higher among Tac-treated patients (69.6% versus 34.8%). It is of note that the true incidence of HTN was higher after the number of patients with a pathological 24-h BP measurement was added to the initial number of patients already known to have HTN. No less than 76.4% of all long-term liver transplanted patients showed HTN. The results were unrelated to cumulative steroid dosage, frequency of antirejection therapy or underlying primary liver disease. In summary, immunosuppression-induced HTN is more common in CyA-treated than Tac-based regimens. Moreover, we found a substantial lack of detection of HTN in long-term liver transplant patients who received an insufficient quality of antihypertensive treatment. These findings have implications for the early diagnosis and treatment of HTN in liver transplant recipients.     

Long-term renal allograft function on a tacrolimus-based, pred-free maintenance immunosuppression comparing sirolimus vs. MMF.

It is not known how different steroid-free immunosuppressive combinations affect renal graft survival and long-term kidney transplant function. Here we sought to compare the impact on graft survival and long-term graft function of two tacrolimus (Tac)-based, prednisone-free maintenance immunosuppressive protocols: Tac/Mycophenolate Mofetil (MMF) vs. Tac/Sirolimus (SRL). Renal transplant patients given induction therapy with IL2-RA and methylprednisolone on days 0, 1 and 2 post-transplant were prospectively randomized to two maintenance immunosuppressive regimens with Tac/MMF (n = 45) or Tac/SRL (n = 37). During the 3-year follow-up the following data were collected: patient survival, renal allograft survival, incidence of acute rejection and glomerular filtration rate (GFR) at different time-points post-transplant. Cumulative graft survival was significantly different in the two groups: one kidney loss in the Tac/MMF vs. six kidney losses in the Tac/SRL (log-rank test p = 0.04). GFR at different time-points post-transplant was consistently and statistically better in the Tac/MMF than in the Tac/SRL group. The slope of GFR decline per month was flatter in the Tac/MMF than in the Tac/SRL group. This study showed that renal graft survival and graft function were significantly lower in the combination of Tac/SRL than Tac/MMF.