儿童肾移植术后的免疫抑制治疗

目的 探讨长期存活的儿童肾移植受者不同免疫抑制方案的有效性与安全性.方法 回顾性分析34例存活5年以上的儿童受者免疫抑制剂使用情况,按所使用的免疫抑制剂不同分为5组:A组:环孢素A+强的松;B组:环孢素A+硫唑嘌呤+强的松;C组:环孢素A+霉酚酸酯+强的松;D组:他克莫司+硫唑嘌呤+强的松;E组:他克莫司+霉酚酸酯+强的松.结果 术后按Kaplan-Meier法得出1、3、5年人/肾存活率分别为100%/97%、91%/87.8%、84.4%/80.9%.术后1、3、5年时肾存活的33例、30例和28例中,服用环孢素A者为16/33(48.5%)、18/30(60%)、15/28(53.6%),服用他克莫司者为17/33(51.5%)、12/30(40%)、13/28(46.4%);服用硫唑嘌呤者为7/33(21.2%)、7/30(23.3%)、9/28(32.1%),服用霉酚酸酯者为26/33(78.8%)、21/30(70%)、17/28(60.7%).移植1年后环孢素A血浓度谷值100～150 ng/ml,他克莫司血浓度1.5～3 ng/ml.各组不同时期的环孢素A和他克莫司剂量和浓度均无明显差异.霉酚酸酯剂量维持在10 mg·kg-1·d-1,强的松5～10 mg/d.服药不依从者占30%.移植肾丢失5例,原因分别为排异反应1例,移植肾带功能死亡4例(肺部感染和药物性肝功能损害各2例).并发症包括高血压(35.7%)、高血脂(28.6%)、感染(17.9%)、牙龈增生(14.3%)、多毛(10.7%)、糖尿病(3.6%).结论 环孢素A/他克莫司、霉酚酸酯、强的松三联免疫抑制治疗是儿童肾移植受者主要的抗排异方案,须定期监测血药浓度,个体化调整剂量.     

儿童肾移植18例报告

目的　探讨儿童肾移植适应证的选择、围手术期处理 ,以及肾移植对儿童生长发育、心理及生理上的影响。方法　回顾分析 1985年以来 18例儿童肾移植的临床资料 ,年龄 13～ 16岁 ,平均年龄 (15± 1.3)岁 ,其中 13岁 3例 ,14岁 4例 ,15岁 6例 ,16岁 5例。体重 2 2～ 4 3kg ,平均 (31±6 .4 )kg。结果　儿童肾移植占同期肾移植总例数的 1.4 % ,移植手术时间 1.5～ 3h ,无外科并发症。术后 3个月内发生急性排斥反应 5例 (2 7.8% ) ,1年人 /肾存活率为 10 0 % / 10 0 % ,3年 86 .7% /73.3% ,5年 80 .0 % / 70 .0 %。术后第 1年体重增加 6～ 10kg ,身高增高 2～ 5cm。 2例男性受者已结婚 ,1例育有一子一女 ,子女均健康。主要并发症为高血压 (44 .4 % )、白内障 (11.1% )、糖尿病(16 .7% )。死亡 2例 ,死因分别为肺部感染、肝功能损害。结论　肾移植是治疗儿童终末期肾功能衰竭的有效治疗手段。根据体重和年龄选择合适的植肾部位与血管吻合方式。环孢素A和FK5 0 6用量较成人大 ,应严密观察其血药浓度 ,激素用量宜减少。定期随访、提高患儿依从性是长期存活的关键     

儿童肾移植效果及影响因素分析

目的 探讨儿童肾移植手术、围手术期处理及术后免疫抑制治疗特点,提高治疗效果.方法 回顾性分析我院1986年1月至2008年9月间66例儿童肾移植患者的临床资料.结果 本组受者术后1、3、5、10年人存活率分别为100%、90.9%、87.8%、68.2%,术后1、3、5、10年肾存活率分别为93.9%、86.3%、84.8%、65.1%.术后1年体重增加4～12.5 kg,身高增加2～6cm.术后1年急件排斥反应20例(30.3%).术后1年并发症包括高血压27例(40.9%)、多毛15例(22.7%)、药物性肝损11例(16.7%)、牙龈增生10例(15.2%)、肺部感染10例(15.2%)、骨髓抑制5例(7.6%)、单纯性疱疹4例(6.1%)、糖尿病3例(4.5%).结论 肾移植是儿童终末期肾病有效的治疗手段.严格的组织配型、适宜的手术时机和良好的围手术期处理、个体化使用免疫抑制剂和良好的依从性是取得良好效果的关键.     

小儿双供肾整体移植的临床疗效分析

目的总结和分析小儿双供肾整体移植的临床疗效, 并探讨经验和教训。方法回顾性分析天津市第一中心医院肾移植科2011年7月至2022年1月收治的36例小儿双供肾整体移植患者的临床资料。主要观察移植肾存活率、移植肾丢失以及泌尿系统并发症发生率, 还包括蛋白尿, 出血等。随访3年, 观察患者生存率及血清肌酐变化。结果术后1年、3年的移植物存活率均为83%(30/36), 移植受者存活率均为100%(36/36), 移植物长期存活的30例受者中, 术后3年血肌酐水平持续下降。移植肾丢失发生率为16.7%(6/36), 其他并发症包括泌尿系统并发症16.7%(6/36)、出血11.1%(4/36)等。蛋白尿的发生比例逐步下降, 大部分在随访期间消失。结论小儿双供肾整体移植具有良好的长期移植肾功能和存活率, 是一个增加供体库的可行、有效方法。     

儿童肾移植的现状和发展

儿童肾移植一般指受者年龄在18岁以下的移植,在国际上大约开始于80年代中期,晚于成人。肾移植是公认的终末期肾病(ESRD)患儿的治疗方法,儿童和青少年成功的肾移植不仅能够缓解尿毒症症状,而且能改进、甚至完全纠正骨骼发育迟缓、性成熟障碍、认知和心理功能损害。近年来随着外科手术技术的提高、组织配型的应用、免疫抑制药物的改进以及对术后护理的加强,儿童肾移植的成功率日益提高[1,2]。现就儿童肾移植的一些具体问题作一综述,以了解儿童肾移植的现状和发展。1儿童肾移植的存活率对于各年龄段的患儿,接受肾移植后的生存率都大于接受透…     

儿童肾移植现状与展望

肾移植是我国实体器官移植中数量最多的移植种类,每年为5000～10000例。其中,绝大多数移植受者为成年人,大量的临床经验也来自于成人肾移植。儿童肾移植数量较少,但其具有自身的特点,在临床处理及随访的诸多环节中,不能完全等同于成人肾移植,本文特对儿童肾移植的现状及展望行总结。     

儿童肾移植中的热点问题

自美国1954年成功地进行了第一例同卵双生肾移植手术以来,全球已累计近百万人接受过各类移植,同时随着各类新型免疫抑制剂的运用,移植物的长期存活率逐年提高。全球已施行肾移植50余万例,最长存活已达41年。我国肾移植开始于上世纪70年代,移植数稳步增加,目前,每年肾移植数超过5000例,数量仅次于美国,最长存活超过20年。尽管我国移植数量稳步增加,必须看到同世界领先水平相比较,我国的移植生存率还存在着很大差距。儿童肾移植一般指受者年龄在18岁以下的移植,近年来,已逐渐成为儿童终末期肾病（ESRD）最有效的治疗方法,随着强有力的免疫抑制药物的问世及手术技术更趋成熟,儿童肾移植的近远期疗效不断提高。局灶节段性肾小球硬化（FSGS）、先天性肾病综合征（CNS）、肾炎、梗阻性尿路疾病的移植肾生存率得到明显改善;多囊肾（PKD）、肾消耗病、溶血尿毒综合征（HUS）、返流性肾病的移植肾生存率保持稳定。美国器官资源共享网络（UNOS）已有数千名儿童肾移植经验的积累。而国内目前儿童肾移植发展相对较缓慢,尤其在低年龄组儿童,开展儿童肾移植较成人的困难更大,严格的配型选择、适宜的手术方式和围手术期处理、恰当的免疫抑制策略和良好的依从性是取得良好效果的关键。     

儿童肾移植临床免疫抑制用药探讨

目的　探讨儿童肾移植免疫抑制治疗特点。方法　回顾性分析 31例儿童肾移植患者(男 18例,女 13例)的临床资料。根据起始免疫抑制方案不同,分为 3组:A组(环孢素A+硫唑嘌呤+泼尼松)7例;B组(环孢素A+霉酚酸酯 +泼尼松)17例;C组 (他克莫司 +霉酚酸酯 +泼尼松)7例。统计 3组免疫抑制药物调整及维持剂量、移植肾功能变化和术后并发症。结果　1年人 /肾存活率为100% /96.8%,3年人 /肾生存率为94.4% /88.9%。三组各观察点肌酐实测值差异无显著性意义 (P<0.05)。他克莫司组药物副作用小且能保持良好的肾功能。泼尼松调整幅度大、维持量小,与其他组差异有显著性意义(P<0.01)。结论　肾移植是儿童终末期肾病的有效治疗措施。遵循儿童个体差异的免疫抑制治疗是移植后预防排斥的重点。他克莫司、霉酚酸酯、泼尼松三联抗排斥治疗是儿童肾移植理想的免疫抑制治疗方案。     

肾移植术后人肾存活患儿生长发育的队列研究

目的探讨儿童肾移植后生长发育的临床特征及影响移植后追赶性生长的因素。方法收集2017年7月至2019年11月由广州市妇女儿童医疗中心和中山大学附属第一医院合作进行肾移植手术的受者术后随访的病历资料，生长发育指标：身高生长速率（ΔHtSDS）、末次身高标准差（HtSDS），生存指标：血肌酐、血清白蛋白、Hb、血钙、血磷、尿蛋白/肌酐、尿RBC计数、血压，并发症，用药情况（糖皮质激素、免疫抑制剂、降压药和骨化三醇等）。结果接受移植术受者18例，中位随访时间17.5（11，24.5）月，肾移植后第1年ΔHtSDS为0.8（0.1，1.2），追赶率为61%，第2年ΔHtSDS为-0.1（-03，0.4），末次随访HtSDS为-1.94±0.99，达标率50%。HtSDS移植前与末次随访呈正相关（r=0.64，P=0.005），与随访12个月时的ΔHtSDS呈负相关（r=-0.61，P=0.008）。随访期人肾存活率均100%，8例出现并发症，其中3例重症感染、4例抗体介导性排异反应、1例原发肾病复发。糖皮质激素（GC）累积量（143.6±86.6）mg·kg-1，每天剂量为（0.30±0.15）mg·kg-1，使用降压药10例，骨化三醇9例。多因素分析显示，移植前HtSDS、移植年龄和血压是肾移植后身高追赶性生长的危险因素，降压药的使用是身高追赶性生长的独立保护因素。结论肾移植受者术后随访终点身高低于同年龄同性别正常儿童身高2个标准差，移植前较低的HtSDS、较小的移植年龄及正常低限的平均动脉压是儿童肾移植后提高ΔHtSDS的有利因素，降压药的使用是肾移植后身高追赶性生长的保护因素。     

肾移植儿童的惊厥

1965年6月～1987年12月美国辛辛那提(Cinc-inati)儿童医院为154例儿童行207例次肾移植,其中48例(31%)74例次有惊厥发作。仅发生于移植前者17例(35%),仅发生于移植后者23例(48%),     

The long-term outcomes of pediatric kidney transplantation: a single-centre experience in China

Abstract:  To explore the long-term outcomes of paediatric kidney transplantation and the effects of renal allograft on growth, education, employment, marriage and procreation. Twenty-seven children with ESRD received the renal allograft from 1985 to 2001. The patient and kidney survival rate, renal function, growth and employment, etc., were reviewed retrospectively. The average follow-up period was 10.3 ± 4.4 yr. The one-, three-, five- and 10-yr graft survival rates were 96.3%, 88.9%, 81.5% and 66.7%, respectively, and the corresponding patient survival rates were 100%, 92.6%, 85.2% and 68.8%. The body weight gain was 4–10 kg in one-yr post-operative and the height increased 0–2 cm for girls and 2–5 cm for boys. A total of 44.4% of the recipients accomplished their education above junior high school. The employment rate was 46.2% in males, and 57.2% in females. Twelve patients were married. Non-adherence occurred in 30% of the recipients. Forty percent of the surviving recipients developed complications. Seven patients died. More attention should be paid to non-adherence of medications and more supports from the society are required to improve the life quality of paediatric recipients, especially in employment and education.     

Treatment strategies in pediatric solid organ transplant recipients with calcineurin inhibitor-induced nephrotoxicity

Although short-term kidney allograft survival has improved significantly since the introduction of the calcineurin inhibitors (CNI) cyclosporine A (CsA) and tacrolimus, long-term transplant survival remains a major concern, chronic allograft nephropathy (CAN) being the principal reason for graft loss after the first post-transplant year. This is particularly major for pediatric renal transplant recipients because of their higher life expectancy compared with adults. The mechanisms leading to CAN are multiple, including acute and chronic alloimmune responses and nephrotoxicity of CNIs. CNI-induced nephrotoxicity is also a long-term concern in other pediatric solid organ transplant recipients, such as liver and heart. Prevention of allograft nephropathy requires a balance of maintaining adequate immunosuppression, while avoiding the toxic effects of CNIs. Regimens that are based on mycophenolate mofetil (MMF) alone or in combination with newer agents may allow for reduced reliance on CNIs and thus may represent an effective treatment paradigm for long-term maintenance of a renal allograft. From the available data it appears that the currently safest treatment strategy in pediatric renal and heart transplant recipients with CNI toxicity is an MMF-based therapy with low-dose CNIs +/- low-dose steroids, while in pediatric liver transplant recipients, CNI-free MMF-based immunosuppressive therapy with or without steroids appears feasible in a significant subset of patients. In renal transplant recipients, the benefit of a CNI-free MMF/steroid therapy on renal function is gained at the cost of increased rejection in a subset of patients, although the relative importance of rejection vs. overall renal function requires further clinical investigation. The introduction of mammalian target of rapamycin (mTOR) inhibitors provides an opportunity for unique CNI-sparing regimens that combine two antiproliferative agents (MMF and TOR inhibitors). It is possible that a sirolimus-based CNI-free immunosuppressive regimen in terms of renal transplant survival is superior to CNI minimization, where the detrimental effects of CNIs on allograft function and structure are still operative, albeit to a lesser degree. Substitution of CNIs by mTOR inhibitors is therefore promising, but requires validation in long-term studies in large cohorts.     

Renal function outcome in pediatric liver transplant recipients

The orthotopic liver transplantation (OLT) allows survival of children followed for severe hepatic injury, provided that the immunosuppressive treatment is prolonged. The nephrotoxicity of cyclosporine predicts the long-term outcome of the adult patients receiving a liver transplant. The aim of this study was to determine the long-term outcome of renal function in children receiving OLT. This study included 12 children, with a median for age of 7.1 yr (2-15 yr) at the time of OLT. The duration of follow-up was at least 4 yr, being 7 yr in 10 patients and more than 10 yr in seven. Renal function was evaluated with the serum level of creatinine, calculated glomerular filtration rate (cGFR), and measurement of glomerular filtration rate using chrome 51 ethylenediaminetetraacetate ((51)Cr EDTA) clearance performed at least once during follow-up. The doses and the serum concentrations (C(0)) of cyclosporine were reported at each study time. The cGFR decreased significantly 2 yr after the OLT [median (range): 106 mL/min/1.73 m(2) (71-150) at the time of OLT vs. 85 mL/min/1.73 m(2) (57-128) 2 yr after the OLT, p = 0.03], and decreased again between 7 and 10 yr after OLT [median (range): 99 mL/min/1.73 m(2) (76-125) 7 yr after OLT vs. 81 mL/min/1.73 m(2) (66-140) 10 yr after OLT, p = 0.04]. Six patients developed chronic renal failure (cGFR from 57 to 80 mL/min/1.73 m(2)) 2 yr after OLT associated with high doses of cyclosporine [median (range): 8.8 mg/kg/day (3.5-13)]. The cGFR overestimated renal function by 16% compared with the isotopic measurement of GFR (p = 0.03). Using the (51)Cr EDTA measurement, six of seven patients followed up more than 10 yr after OLT presented mild (n = 3) or moderate (n = 3) chronic renal failure. In our study, the majority of OLT recipients developed a chronic renal failure 10 yr after transplantation. Cyclosporine seems to be the most important factor responsible for the impairment of renal function. The use of the mycophenolate mofetil, a new immunosuppressive agent, allowing a reduction in the dose of cyclosporine, could minimize renal dysfunction. While awaiting the results of a prospective long-term study, close drug monitoring is advised.     

儿童肾移植21例报告

目的 探讨肾移植对儿童终末期肾病(ESRD)的疗效及其手术处理、免疫抑制剂应用方法。方法 总结肾移植患儿的临床资料、植肾手术方法、免疫抑制剂应用和随访情况。结果 患儿术后早期平均肾功能恢复时间为5．6d。1、3、5年人／肾存活率分别为95、2％／95．2％、86．7％／73．3％,72．7％／63．6％。最长存活12年。其中1例发生超急性排斥反应,5例发生急性排斥反应,3例出现移植物功能延迟恢复,3例死亡。术后采用了免疫抑制治疗。术后主要并发症有：高血压(48％)、糖尿病(19％)、感染(19％)、药物性肝损害(14％)。结论 肾移植是治疗儿童：ESRD最为理想的方法。儿童可以适应成人肾脏的移植。术后免疫抑制治疗建议联合应用泼尼松 霉酚酸酯 他克莫司。     

Outcome of renal transplantation in children: a multi-center national report from Iran

The outcome of pediatric renal transplantation was previously reported by a single-center study at the year 2006. Therefore, we aimed to evaluate and report the characteristics and outcome of renal pediatric renal transplantation in a multi-center nationwide study. In this nationwide report, medical records of 907 children (≤18yr) with renal transplantation in eight major pediatric transplant centers of Iran were recorded. These 907 patients received a total of 922 transplants. All children who failed to follow-up were excluded. Rather than baseline characteristics, graft and patient outcomes were considered for survival analysis. For further analysis, they were divided into two groups: patients who had graft survival time more than 10yr (n=91) and the ones with graft survival time of equal or less than 10yr (n=831). Of 922 recipients, 515 (55.8%) were boys and 407 (44.2%) were girls with the mean age of 13.10 (s.d.=3.54) yr. DGF and AR were occurred in 10% and 39.5% of the transplanted children, respectively. Transplantation year, dialyzing status before transplantation, DGF, and AR were significant enough to predict graft survival in cox regression model (overall model: p<0.001). Nowadays, there is a successful live donor pediatric renal transplantation in Iran. Graft survival has improved in our recipients and now the graft survival rates are near to international standards.     

Pediatric heart transplantation

Heart transplantation is now a treatment option with good outcome for infants and children with end-stage heart failure or complex, inoperable congenital cardiac defects. One-year and 5-year actuarial survival rates are high, approximately 75% and 65%, respectively, with overall patient survival half-life greater than 10 years. To date, survival has been improving as a result of reducing early mortality. Further reductions in late mortality, in part because of graft coronary artery disease and rejection, will allow achievement of the goal of decades-long survival. Quality of life in surviving children, as judged by activity, is usually "normal." Somatic growth is usually at the low normal range but linear growth can be reduced. Of infant recipients, 85% evaluated at 6 years of age or older were in an age-appropriate grade level. Long-term management of childhood heart recipients requires the collaboration of transplant physicians, given the increasing number of immunosuppressive agents and the balance between rejection and infection. Currently, recipients are maintained on immunosuppressive medications that target calcineurin (eg, cyclosporine, tacrolimus), lymphocyte proliferation (eg, azathioprine, mycophenolate mofetil [MMF], sirolimus) and, in some instances antiinflammatory corticosteroids. Emerging evidence now suggests a favorable immunologic opportunity for transplantation in childhood and, conversely, a higher mortality rate in children who have had prior cardiac surgery. Further studies are needed to define age-dependent factors that are likely to play a role in graft survival and possible graft-specific tolerance (eg, optimal conditions for tolerance induction and how immunosuppressive regimens should be changed with maturation of the immune system). As late outcomes continue to improve, the need for donor organs likely will increase, as transplantation affords a better quality and duration of life for children with complex congenital heart disease, otherwise facing a future of multiple palliative operations and chronic heart failure.     

Autoimmune hepatitis as a late complication of liver transplantation

BACKGROUND: The development of de novo autoimmune hepatitis as a long-term complication after liver transplantation has been recently reported. The authors describe five liver allograft recipients who developed chronic hepatitis associated with autoimmune features. METHODS: Five of 155 liver transplant recipients at risk (2.5%) developed this particular form of graft dysfunction. The authors review the clinical records, liver histology, therapy, and outcome of these five patients. RESULTS: Patients included two boys and three girls. Median age at transplantation was 3.5 years (range, 0.5-14 years), median age at presentation was 9 years (range, 2-17 years), and median interval after transplantation was 5.1 years (range, 1.5-9 years). Indications for liver transplant included biliary atresia in four patients and primary sclerosing cholangitis in one patient. At the time of presentation, all patients were receiving cyclosporine as their primary immunosuppressive agent. Only one patient had a history of rejection, which had resolved. All patients presented with increased transaminase levels, and one had a mildly elevated conjugated bilirubin level. Only one patient had constitutional complaints. Acute and chronic rejection, viral hepatitis, vascular insufficiency, and biliary tract obstruction were excluded. Antinuclear antibody levels were elevated in four patients (titer range, 1:160-1:640), one of whom also had positive antismooth muscle antibody (titer 1:80) results. The fifth patient had an elevated serum total protein level. Histologic analysis of liver biopsy samples from the five patients showed findings consistent with chronic autoimmune hepatitis. All patients were treated with standard therapy for autoimmune hepatitis, which included daily steroids and azathioprine. Cyclosporine doses were reduced in three patients and eliminated in two. All patients responded with normalization (n = 2) or improvement (n = 3) of liver transaminases within the first 3 months of therapy. Histologic analysis of the 3-month follow-up liver biopsy was normal (n = 2) or showed improvement in inflammation (n = 2). Two patients developed acute allograft rejection within 6 to 12 months after discontinuation or reduction in cyclosporine. CONCLUSIONS: Autoimmune hepatitis occurs after liver transplantation in patients without a previous history of autoimmune hepatitis. The risk of developing autoimmune hepatitis appears to be greater in children after liver transplantation than in the general pediatric population. Standard therapy for autoimmune hepatitis is effective.     

Use of cyclosporine in pediatric renal transplant recipients

Cyclosporine and prednisone were used in combination to produce immunosuppression in 18 pediatric recipients of renal allografts. Ten children received cadaveric kidneys and eight received kidneys from living related donors. With a mean follow-up of 16.5 months (range 7 to 33 months), the patient survival rate is 100% (18 of 18) and the graft survival rate is 83% (15 of 18). Two grafts were lost for nonimmunologic reasons. Currently the group mean (+/- SE) serum creatinine concentration is 1.22 +/- 0.11 mg/dl and creatinine clearance is 69.3 +/- 4.79 ml/min/1.73 m2. Cyclosporine nephrotoxicity has not caused irreversible allograft injury nor led to graft loss in this population. The incidence of treated rejection episodes has been 39% (seven of 18). Only 39% (seven of 18) of children have required hospital readmissions since the initial transplant discharge. There have been no opportunistic infections. In the 15 children with functioning grafts, some linear growth has occurred in 10 of 11 prepubertal and two of four postpubertal patients. Cyclosporine and prednisone have constituted a safe, efficacious immunosuppressive regimen for pediatric renal allograft recipients. Longer follow-up will be necessary to confirm whether these advantages persist beyond 2 years.