在移植肾功能稳定的受者中主动撤除环孢素A的临床研究

目的 研究在移植肾功能稳定的受者中主动撤除环孢素A(CSA)对急性排斥反应发生率及肾功能的影响.方法 选择35例肾功能稳定的肾移植受者,其中尸体肾移植23例,亲属活体肾移植12例.除2例为再次肾移植外,其余均为初次肾移植.分别在肾移植术后6个月～6年时停用CsA,平均为术后(13.3±9.1)个月.撤除CsA后免疫抑制方案为:霉酚酸酯(MMF)+西罗莫司(SRL)+泼尼松(Pred).撤除CsA前有9例做了移植肾穿刺活检,8例测定了抗HLA抗体.结果 对35例受者随访6个月～4.5年,平均14.8个月.撤除CsA前、后血肌酐平均值分别为(88.1±15.5)μmol/L和(92.3±23.7)/μmol/L(P0.05).撤除CsA后,有2例经活检证实发生急性排斥反应,治疗后均逆转;CsA所致的毒副作用,如牙龈增生、糖耐量异常和多毛症等明显改善.9例移植肾活检中,有3例肾功能正常的受者已出现轻度慢性移植肾肾病表现.抗HLA抗体检测中,7例阴性者在撤除CsA前、后肾功能无明显变化.1例抗HLA抗体呈强阳性者在撤除CsA后进展为慢性移植肾肾病,恢复血液透析.结论 对移植肾功能稳定的受者在移植6个月后撤除CsA,转换为"霉酚酸酯+西罗莫司+泼尼松"的免疫抑制方案是安全的,不增加急性排斥反应风险;撤除CsA有利于消除一些与其相关的毒副作用;对抗HLA抗体呈强阳性者.撤除CsA后很难改变肾功能的进展.     

他克莫司在出现环孢素A毒副反应的肾移植受者中的应用

自环孢素A(CsA)应用于临床器官移植受者以来,排斥反应的发生率大大降低,移植肾的存活率得到了显著的提高,但随之而来的与CsA相关的毒副反应包括肾毒性、心血管不良事件等的高发生率不仅严重影响了受者的生活质量,也影响了移植肾的长期存活.他克莫司(Tac)作为一种更强效的钙调磷酸酶抑制剂(CNI),可比CsA更有效的预防和治疗排斥反应,同时不良反应的发生率更低.那么,对于出现CsA毒副反应的肾移植受者,是否可转换为Tac治疗呢?     

稳定期肾移植受者将他克莫司普通剂型转换为缓释剂型对移植肾功能的影响

目的观察稳定期肾移植受者由普通剂型他克莫司(Tac)转换为缓释剂型Tac后对移植肾功能的影响。方法回顾性分析山西省第二人民医院2011年12月至2019年6月由普通剂型Tac转换为缓释剂型Tac的83例稳定期肾移植受者,随访12~36个月,同时匹配83例继续服用普通剂型Tac的稳定期肾移植受者作为对照组。观察稳定期肾移植受者由普通剂型Tac转换为缓释剂型Tac后肾功能、谷值浓度个体内变异度(IPV)及依从性的变化、排斥反应的发生率及移植肾和移植受者的存活率。结果普通剂型Tac转换为缓释剂型Tac时间为移植后(42.76±30.50)个月,转换后24个月血清肌酐(SCr)明显低于转换前(P=0.013),估算肾小球滤过率(eGFR)明显高于转换前(P=0.005)。试验组较对照组在转换后36个月SCr明显降低(P=0.017),eGFR明显增高(P=0.038)。试验组转换前免疫抑制剂治疗障碍量表(ITBS)得分为(20.23±2.89)分,转换后为(17.63±3.08)分(P=0.000);Tac每日剂量转换前是(2.09±0.84)mg,转换后为(2.10±0.83)mg;Tac谷值浓度转换前为(7.22±2.84)ng/mL,转换后显著降低,人/肾均健康存活。结论稳定期肾移植受者由普通剂型Tac转换为缓释剂型Tac肾功能保持稳定且较普通剂型Tac相对更好,依从性明显改善,谷值浓度个体内变异度明显降低,长期服用的临床疗效和安全性良好。     

儿童肾移植46例报道

目的探讨儿童肾移植的手术特点、术后并发症及免疫抑制治疗方案。方法回顾性研究1998年2月至2004年12月46例儿童肾移植患者的临床资料。观察受者及移植肾存活情况,受者生长发育情况及术后并发症。结果46例儿童肾移植后发生急性排斥反应10例,肾功能延迟恢复4例,尿漏1例,肝功能损害8例,肺部感染8例,全骨髓抑制3例,粒细胞减少2例,输尿管坏死1例,移植肾动脉狭窄1例。术后4周所有患者肾功能均恢复正常。术后1年人和移植肾存活率均为100%,3年人和移植肾存活率分别为100%和97.4%。结论肾移植是治疗儿童终末期肾病的有效手段。儿童肾移植术后急性排斥发生率高,免疫抑制治疗应根据不同个体的特点制定不同的方案。     

肾移植前对致敏患者干预治疗的方案及疗效分析

目的 总结和探讨肾移植前致敏患者干预治疗的方案及疗效分析.方法 选择2008年至2011年接受肾移植的致敏受者43例,根据术前群体反应性抗体(PRA)水平分为轻度致敏组和高度致敏组,术前经血浆置换、输注静脉用免疫球蛋白(IVIG)的干预治疗,经过HLA配型,联合应用抗人胸腺细胞免疫球蛋白(ATG)诱导治疗,应用他克莫司(Tac)、吗替麦考酚酯(MMF)和泼尼松的免疫抑制方案,术后定期检测PRA水平.所有受者随访12～36个月,观察受者/移植肾存活率,急性排斥反应的发生率,移植肾功能和PRA水平的变化,以及进行移植肾穿刺活检.结果 经干预治疗后,轻度致敏组中14例PRA完全转阴,高度致敏组中5例PRA完全转阴,其余受者PRA水平均较干预治疗前明显下降(P＜0.05).术后两组受者均出现PRA水平的爬升.轻度致敏组和高度致敏组的人存活率分别为95.6％和90％,移植肾存活率分别为82.6％和70％.轻度致敏组有3例活检证实发生急性细胞性排斥反应,高度致敏组有5例活检证实发生急性排斥反应,急性细胞性排斥反应均经甲泼尼龙冲击治疗3～5 d后逆转.两组共10例受者出现血肌酐缓慢爬升,经移植肾穿刺活检发现慢性移植肾肾病的表现.结论 血浆置换和输注IVIG的干预治疗,良好的HLA配型,ATG诱导治疗,以及应用Tac+ MMF+泼尼松的免疫抑制方案是致敏受者肾移植成功的前提.     

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.     

他克莫司与环孢素A在高致敏肾移植受者中的应用比较

目的 观察和比较高致敏肾移植受者应用他克莫司(FK506)与环孢素A(CsA)的有效性和安全性.方法 根据术后免疫抑制方案的不同,将147例高致敏肾移植受者(其中术前群体反应性抗体＞50%的首次肾移植受者59例,2次肾移植受者88例)分为FK506组(53例)和CsA组(94例),两组的免疫抑制方案分别为FK506(或CsA)+霉酚酸酯+泼尼松.观察并分析两组受者术后移植肾存活率、血肌酐水平以及并发症的发生率.结果 FK506组术后1、3和5年的移植肾存活率(86.8%、82.3%和75.3%)略高于CsA组(81.9%、75.4%和66.9%),但差异无统计学意义(P＞0.05);FK506组术后1年时血肌酐水平为(100.72±15.88)μmol/L,CsA组为(117.29±11.77)μmol/L,两组比较,差异有统计学意义(P＜0.01);FK506组与CsA组相比,术后急性排斥反应、慢性排斥反应、肝功能损害、高血压和高血脂的发生率显著降低(P＜0.05),而高血糖的发生率明显升高(P＜0.01),两组移植肾功能延迟恢复和感染的发生率无明显差异(P＞0.05).结论 FK506与CsA相比,能有效降低高致敏受者肾移植术后急、慢性排斥反应的发生率,减少术后并发症的发生,提高移植肾的长期存活率,对高致敏肾移植受者是非常有效和安全的.     

移植肾功能延迟恢复对长期存活的影响

目的 探讨移植肾功能延迟恢复对肾移植受者人／肾长期存活的影响。方法 回顾分析５７３例肾移植中发生的７０例移植肾功能延迟恢复受者的人／肾存活情况及其相关危险因素。结果 ７０例患者总的１、３、５年人存活率分别为７７．１％、４７．６％、３７．５％,肾存活率分别为７１．４％、４０．５％、１５．０％,明显低于同期未发生肾功能延迟恢复的受者,但未合并排斥反应的移植肾功能延迟恢复者存活率并不受影响,合并排斥反应     

影响再次肾移植临床效果的主要因素

目的:探讨影响再次肾移植临床效果的主要因素.方法:报告我院115例再次肾移植患者的临床资料,并与同期首次移植患者的人/肾存活率对比观察.结果:两组间1、3、5年受者存活率的差异无统计学意义;而移植肾的存活率再次移植组明显低于对照组(P<0.05).再次肾移植受者淋巴毒试验<59例,5%～10(例,>10%9例,其移植肾存活率分别为72%、31%、0%.再次肾移植受者PRA<10C例,>10例,其术后急性排斥反应发生率分别为30.2%、75.0%.术后排斥反应、感染、肝功能损伤的发生率,再次移植组高于首次移植组(P<0.05);高血压、高血脂、糖尿病的发生率两组未见显著性差异.结论:再次移植肾存活率低于首次移植;术前PRA、淋巴毒水平是影响再次肾移植效果的主要因素;术后排斥反应、感染及肝功能损伤的发生率高于首次肾移植.     

儿童肾移植后应用他克莫司为主的免疫抑制方案的临床观察

目的 总结儿童肾移植受者术后应用以他克莫司(Tac)为主的免疫抑制方案的体会.方法 35例受者,年龄为(12.4±1.5)岁(10～18岁),均接受成人尸体供肾,其中33例为首次肾移植,2例为再次肾移植.所有受者肾移植后均采用Tac、霉酚酸酯(MMF)和糖皮质激素预防排斥反应.术后3个月内、3～6个月、6～12个月时Tac的用量分别为0.15～0.32 mg·kg-1·d-1、0.12～0.15 mg·kg-1·d-1、0.07～0.11 mg·kg-1·d-1,Tac浓度谷值分别为(10.5±1.4)μg/L、(8.5±0.8)μg/L、(7.2±0.5)μg/L.35例中,18例术前进行免疫诱导治疗.结果 术后移植肾1、3、5年存活率分别为100%、97.1%、93.9%,受者1、3、5年存活率分别为100%、94.1%、90.9%.术后第1年受者的体重增加了(6.6±2.2)kg,身高增加了(3.7±1.1)cm.术后共有7例(20.0%,7/35)发生急性排斥反应.治疗后均逆转.其他并发症包括高血压11例(31.4%),高血脂5例(14.3%).药物性肝损伤4例(11.4%),肺部感染4例(11.4%),骨髓抑制2例(5.7%),糖尿病2例(5.7%),单纯性疱疹1例(2.8%),受者均无牙龈增生及多毛症.结论 儿童肾移植受者采用Tac、MMF和糖皮质激素预防排斥反应有效,应注意Tac和激素的用量和用法.术前行免疫诱导治疗对降低急性排斥反应的发生有益.     

Switching from cyclosporine to tacrolimus in patients with chronic transplant dysfunction or cyclosporine-induced adverse events

BACKGROUND: Progressive renal-function decline caused by chronic allograft nephropathy is the main cause of long-term failure after kidney transplantation. Moreover, chronic cyclosporine (CsA)-induced nephrotoxicity is an important nonimmunologic factor contributing to graft dysfunction and loss, and adverse events may require CsA withdrawal. METHODS: Tacrolimus (Tac) replaced CsA-based immunosuppression in 133 transplant patients (114 kidney, 15 kidney-pancreas, 4 pancreas after kidney) with progressive loss of renal function (71% of patients) or CsA intolerance (29% of patients) not responding to CsA dose-lowering. The primary end-points of this prospective study focusing on renal function were the safety and efficacy of Tac immunosuppression. RESULTS: Tac was generally well tolerated but definitively withdrawn for 23 (17%) patients (21 graft failures, 1 case of diabetes, and 1 case of clinical intolerance). Differential creatinemia (creatinemia-nadir creatinemia after transplantation) decreased significantly from 85.4+/-9.8 to 39.0+/-7.5 mumol/L (P<0.001; mean+/-SEM) after 1 year and 3.6+/-18.1 mumol/L (P<0.01) after 4 years. For patients with CsA intolerance, switch to Tac improved intolerance symptoms in all cases. Blood urea, creatinine clearance, blood total cholesterol, and triglycerides improved significantly, and the percentage of hypertensive patients remained stable with no de novo hypertension. During follow-up, one patient experienced an acute rejection episode (not histologically proven), and four died. Twenty-one (16%) transplants failed, significantly more frequently in patients with advanced renal impairment before Tac (P<0.0001). CONCLUSION: Switching from CsA to Tac can be an alternative strategy in kidney-transplant patients suffering from chronic allograft dysfunction or CsA toxicity. The persistently improved renal function over several months of evaluation suggests that in these patients, Tac might be less nephrotoxic than CsA and could prolong transplant function despite CsA failure.     

Conversion from cyclosporine A to tacrolimus in pediatric kidney transplant recipients with chronic rejection: changes in the immune responses

BACKGROUND: Tacrolimus (Tac) has immunosuppressant properties similar to those of cyclosporine A (CsA), but it is more potent. At present, however, its immunosuppressive activity in renal transplant recipients with ongoing chronic rejection has not been clarified. METHODS: We studied changes in kidney function, mixed lymphocyte culture, cell-mediated lympholysis, cytotoxic antibodies, lymphocyte population, and cytokine response before and after the conversion from CsA to Tac in 14 pediatric renal transplant recipients with chronic rejection. CsA (5.9+/-0.2 mg/kg/d) was replaced by Tac (0.1+/-0.004 mg/kg/d). RESULTS: Serum creatinine decreased (2.3+/-0.2-1.9+/-0.2 mg/dL, P <0.005), creatinine clearance increased (36.8+/-2.5-46.1+/-4.4 mL/min/1.73 m, P <0.005), and urinary protein excretion decreased (0.4+/-0.01-0.2+/-0.04 g/24 hr, P <0.03) after 6 months, and these values were maintained after 2 years with Tac treatment. During Tac therapy, anti-donor and anti-control mixed lymphocyte culture decreased 38% and 31% (P <0.05), respectively. Cell-mediated lympholysis did not change. CD3 decreased from 87%+/-2% to 80%+/-2% (P <0.005), and CD8 decreased from 34%+/-3% to 27%+/-2% (P <0.005). The switch to Tac decreased the interferon-gamma production in vitro (P <0.05) and increased tumor necrosis factor-alpha levels (P <0.05). The release of interleukin-10 was strikingly augmented with CsA or Tac therapy (P <0.01), but transforming growth factor-beta secretion was similar. CONCLUSIONS: Our data indicate that conversion from CsA to Tac therapy leads to an improvement in renal function without altering key elements of the immunosuppression in children with ongoing chronic rejection.     

Who should be converted from cyclosporine to conventional immunosuppression in kidney transplantation, and why

Twenty-three cadaveric renal allograft recipients with stable but compromised kidney function were electively converted from cyclosporine to azathioprine one year after transplantation. Within a few weeks glomerular filtration rate (GFR) rose by 40% and serum creatinine fell from 171 +/- 12 (mean +/- SEM) to 129 +/- 7 mumol/L. The increase in GFR was due to an increase in effective renal plasma flow of 21%. This suggests that one year of continuous cyclosporine (CsA) therapy does not result in irreversible structural renal damage. Although antihypertensive treatment was not changed, blood pressure fell from 142 +/- 4/90 +/- 3 to 123 +/- 3/77 +/- 2 mmHg. In addition a significant drop in serum cholesterol and triglycerides and an improvement in glucose tolerance were found. The beneficial effects on renal function, blood pressure, and metabolic indices were, however, outweighed by a high incidence of postconversion rejection in recipients of a second allograft. For these patients conversion from CsA to azathioprine seems therefore contraindicated. Recipients of a first kidney allograft can be converted safely, as long-term CsA administration in these patients induced a solid engraftment. The sequelae of the mode of treatment--impaired renal function, hypertension, and metabolic disturbances--are reversible even after late conversion.     

用他克莫司替换环孢素A预防和治疗肾移植后慢性移植肾肾病

目的 观察用他克莫司（FK506）替换环孢素A（CsA）预防和治疗肾移植术后慢性移植肾肾病的有效性和安全性。方法 回顾性分析36例肾移植术后移植肾功能异常，病理检查确诊为慢性移植肾肾病（CAN）患者的临床资料。所有患者术后均采用以CsA为主的免疫抑制方案，临床确诊为CAN后，用FKS06替换CsA。FK506的起始剂量为原CsA剂量的1／50～1／100，维持剂量则根据患者的体重、发病情况、肾移植时间及FK506的血药谷值浓度确定，其他免疫抑制剂用量不变。观察换药后的移植肾功能变化，同时监测血糖、血脂和FK506的血药浓度。结果 用FK506替换治疗6个月后，患者的移植肾功能较替换前明显好转（P＜0．05），胆固醇、甘油三酯较替换前降低（P＜0．05），但血糖升高，出现新发糖尿病2例。结论 用FK506替换CsA可改善移植肾功能，提高移植肾的长期存活率。     

移植肾的病理类型与肾功能及预后的关系——单中心十年经验回顾分析

目的 分析肾移植受者移植肾的病理类型和特征,及其与肾功能和预后的关系.方法 肾移植术后230例受者接受了移植肾穿刺病理活检,分析其病理表现类型和特征,比较不同病理类型和特征受者移植肾穿刺活检时的血肌酐(SCr)水平,随访受者穿刺活检后1年的移植肾功能情况,评价不同病理特征受者的预后.结果 移植术后3个月时接受了程序性肾活检的10例受者中,9例为正常肾组织,1例为移植后IgA肾病.有肾功能损害临床表现的220例受者中,病理表现为交界性改变33例,急性排斥反应(AR)45例,慢性排斥反应(CR)24例,慢性移植肾肾病(CAN)26例,移植后肾炎(PTGN)39例,以上共167例;另外,28例同时有前面两种或两种以上的病理类型表现,还有CNI肾毒性反应8例,BK病毒肾病7例,急性肾小管坏死5例.有5例受者因采集的移植肾组织过少而不能明确诊断.病理诊断为交界性改变、AR、CR、CAN和PTGN的受者,其穿刺活检时的SCr水平分别为(171±17)、(259±25)、(343±33)、(406±67)和(207±26)μmol/L,不同病理类型者的SCr水平两两比较,差异均有统计学意义(P＜0.01).穿刺活检后1年,随访到上述5种病理类型167例受者中的134例(80.2%),其中交界性改变23例、AR 36例、CR 20例、CAN 18例及PTGN37例,分别有1例(3.1%)、8例(18.2%)、8例(22.2%)、6例(33.3%)、5例(13.5%)发生移植肾功能丧失.穿刺活检后1年,上述5种病理类型移植肾功能异常受者的SCr水平与穿刺时SCr水平的差值(△SCr)分别为(-47±20.7)、(-37.3±36.9)、(25.5±24.3)、(13.5±27.7)和(25.2±17.1)μmol/L.结论 移植肾的病理改变复杂多样,结合移植肾穿刺病理活检结果和临床分析进行准确诊断,可以帮助临床选择合适的治疗方案,促进移植肾的长期存活.     

Long-term beneficial effect of tacrolimus conversion on renal transplant recipients

OBJECTIVE: Acute rejection, chronic allograft nephropathy, and cyclosporine (CsA) toxicity remain serious problems for renal transplant recipients and may lead to graft loss. We retrospectively analyzed 34 patients whose biopsies revealed acute and/or chronic allograft rejection, or CsA nephrotoxicity, and who converted from CsA to tacrolimus. PATIENTS AND METHODS: From July 1996 through September 2003, CsA was converted to tacrolimus in 34 renal transplant recipients (26 male, 8 female) with renal biopsy at our hospital. Blood pressure and serum creatinine levels were checked monthly and serum cholesterol, triglyceride, and glutamic-pyruvic transaminase (GPT) levels were checked every three months. RESULTS: A consistently stable and better function after conversion was obtained in a significant portion (24, 71%) of patients. A statistically significant decline in serum creatinine and an improvement in the glomerular filtration rate were found at 3 m, 6 m, 12 m, 36 m, and 72 m after tacrolimus conversion. In 85.7% (12/14) of patients with acute rejection and in 35.7% (5/14) of patients with chronic allograft nephropathy (concomitant with acute rejection in 5), improved or stabilized graft function was noted. In addition, the systolic blood pressure and diastolic BP dropped significantly (P<0.05), while there was no significant change in cholesterol, triglyceride, and GPT levels. CONCLUSION: The beneficial effect of tacrolimus conversion on patients with acute rejection, chronic allograft nephropathy, or CsA nephrotoxicity was demonstrated in long-term follow up. The improvement in both renal function and blood pressure may be of paramount importance in reducing long-term cardiovascular morbidity and mortality.     

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.     

Mycophenolate mofetil substitution for cyclosporine a in renal transplant recipients with chronic progressive allograft dysfunction: the "creeping creatinine" study

BACKGROUND: This study determined whether cyclosporine A (CsA)-treated renal allograft recipients with deteriorating renal function ("creeping creatinine") secondary to chronic allograft nephropathy (CAN) benefit from the addition of mycophenolate mofetil (MMF) to their immunosuppressive regimen, followed by withdrawal of CsA. METHODS: In a controlled, open, multicenter study, CsA-treated renal allograft recipients with progressively deteriorating renal function were randomized to have their CsA discontinued with the concomitant addition of MMF to their regimen (group A) or to continue treatment with CsA (group B). The primary endpoint was the response rate over the 6-month period after withdrawal of CsA in group A or the equivalent time in group B. Response was defined as a stabilization or reduction of serum creatinine (SCr), as evidenced by a flattening or positive slope of the 1/SCr plot and no graft loss. Secondary endpoints included the incidence of acute rejection, graft and patient survival, and changes in selected metabolic parameters. RESULTS: The response rate in the primary intent-to-treat population (n=122) was 58% (36/62) in group A versus 32% (19/60) in group B (P=0.0060). The corresponding percentages of responders in the per-protocol population (n=107) were 60% (36/60) and 26% (12/47), respectively (P=0.0008). There were no acute rejections in group A during the study period. Patients in this group also experienced a significant decrease in total cholesterol. CONCLUSIONS: In patients with progressively deteriorating renal function secondary to CAN, addition of MMF followed by withdrawal of CsA results in a significant improvement in transplant function without the risk of acute rejection.