肾移植术后重症肺部感染的治疗进展

随着器官移植技术的不断发展和完善,肾移植术已成为晚期肾功能衰竭治疗的重要手段.由于肾移植术后运用免疫抑制剂抗排斥反应,肺部感染已成为肾移植术后最主要的并发症,亦是造成移植受者死亡的主要原因.近年来随着新型、强力免疫抑制剂的使用,肺部感染的病原体发生了较大的变化且病情复杂,如何对肾移植术后重症肺部感染患者的治疗已是当务之急.     

曹烨民论治糖尿病肾病终末期经肾移植后合并糖尿病足重症坏疽经验掇萃

糖尿病足发病率逐年增高,2017年全球糖尿病足总患病率为6. 3％.亚洲糖尿病足患病率为5. 5％,且男性高发于女性[1].糖尿病足坏疽是糖尿病肾病终末期经肾移植术后患者并发症之一.肾移植术后患者服用激素及免疫抑制剂预防器官排异反应,久之,排异药物毒副作用累积.加之肾移植术后患者免疫力低下易致感染[2] ,脓毒血症的风...     

肾移植术后肝功能损害的治疗

目的 探讨肾移植术后肝功能损害的治疗。方法 回顾分析34例肾移植术后发生肝功能损害患者的临床资料。结果 经免疫抑制剂调整、抗病毒及护肝治疗，31例痊愈，1例好转，2例发生急性肝功能衰竭死亡。全部病例未发生排斥反应。站论肾移植术后肝功能损害患者应及时调整免疫抑制剂用药方案并加强护肝治疗。     

高度致敏肾移植患者的围术期处理

目的 探讨高度致敏肾移植患者的围手术期处理.方法 对22例高度致敏肾移植患者术前组织配型及预处理,术后抗排异方案以及肾功恢复情况进行研究.结果 17例患者术前经血浆置换3～8次后群体反应性抗体(PRA)降至30%以下,5例患者术前PRA仍大于50%.术后发生超急性排斥反应(HAR)1例(9.9%),抗排异反应未能逆转,予以切除移植肾;急性排斥反应(AR)8例(36.3%),经甲强龙+ATG(ALG)冲击治疗后6例肾功恢复正常,2例转为肾功能延迟恢复(DGF);术后DGF5例(22.7%),予以血液透析+低剂量抗排异药物维持,肾功均恢复正常.结论 避开相应抗体进行良好的组织配型,是高度致敏患者肾移植成功的关键;术前行血浆置换降低高度致敏患者PRA,使用ATG或ALG可降低手术风险,提高排斥反应逆转率.     

60岁以上尿毒症患者的肾移植临床分析（附151例报告）

目的探讨60岁以上老年尿毒症患者肾移植的特点，总结剧手术期经验。方珐回顾性分析2000年1月至2005年11月我院151例60岁以上肾移植患者的围手术期治疗方案，结合随访结果，对手术适应证、组织配型、免疫抑制剂应用等方面作出评价。结果151例肾移植患者尉手术期无死亡病例，人肾存活率达98．68％，术后平均住院23．86d。术后1年人肾存活率达97．61％。结论严格掌握手术适应证和组织配型，优质的供肾是减少老年‘肾移植患者围手术期并发症的前提；应用免疫诱导，合理使用免疫抑制剂，个体化治疗原则是保障人肾存活率的重要手段。     

狼疮肾炎终末期肾病患者肾移植临床分析

目的：探讨系统性红斑狼疮肾炎终末期肾病患者行肾移植术治疗的效果和可行性。方法：统计我院2004年1月～2008年12月间,原发病为终末期狼疮肾病的肾移植患者的临床资料和手术后随访情况进行分析。结果：4例患者均为女性,行移植手术时全身病情稳定,无狼疮活动;手术后均使用免疫抑制剂抗排斥反应;术后平均随访时间41.5个月;至今其中3例移植肾功能良好,未发生排异反应,1例移植肾功能异常者经移植肾病理活检证实为慢性排斥反应,4例均无狼疮肾病复发。结论：终末期狼疮肾病患者肾移植效果良好,肾移植治疗终末期狼疮肾病是有效和可行的。     

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。     

高致敏肾移植受者脱敏治疗的研究进展

人类白细胞抗原(HLA)致敏在过去被认为是肾移植的禁忌证,在过去的30年中,随着脱敏治疗策略和免疫抑制剂的不断进步,越来越多的高致敏患者跨过了这一障碍。然而,高致敏患者肾移植术后仍面临着较高的超急性排斥反应以及抗体介导的排斥反应发生率,制约着高致敏患者肾移植手术的成功及移植物的长期存活。寻找切实有效的脱敏治疗方案是目前器官移植研究的热点问题,本文将从目前的脱敏治疗策略、用于脱敏治疗的新型制剂以及脱敏治疗的获益与风险进行综述,对目前脱敏治疗的方法以及脱敏治疗未来的方向进行讨论,旨在为跨越免疫屏障、提高高致敏患者肾移植手术的成功率及术后受者生活质量提供参考。     

更昔洛韦治疗肾移植术后带状疱疹临床疗效观察

目的探讨更昔洛韦治疗肾移植术后带状疱疹的临床疗效。方法对本院既往收治的10例肾移植术后临床确诊为带状疱疹的患者回顾性分析,探讨更昔洛韦治疗肾移植术后带状疱疹的疗效。结果肾移植术后患者免疫力下降是导致患者发生带状疱疹的主要原因;10例患者均临床治愈,随访半年无复发。结论肾移植术后发生带状疱疹,可适当调整免疫抑制剂剂量,静脉使用更昔洛韦治疗,可有效治疗肾移植术后带状疱疹。     

肾移植术后服用硫唑嘌呤致粒细胞锐减3例

肾移植术后服用硫唑嘌呤致粒细胞锐减３例温州医学院附属第一医院姜丽萍肾移植术后，患者需终身服用免疫抑制剂以减轻或延缓排异反应。临床上常用药物有：类固醇激素、环孢霉素Ａ（ＣｓＡ）、硫唑嘌呤（ＡＺａ）。其中ＡＺａ有较大毒性，易造成骨髓严重抑制。我院１９８５...     

Induction Therapy for Kidney Transplant Recipients: Do We Still Need Anti‐IL2 Receptor Monoclonal Antibodies?

Induction therapy with antilymphocyte biological agents is widely used after kidney transplantation, most commonly T lymphocyte‐depleting rabbit‐derived antithymocyte globulin (rATG) or an IL‐2 receptor antagonist (IL2RA). Early randomized trials showed that rATG or IL2RA induction reduces early acute rejection, prompting recommendations by Kidney Disease Improving Global Outcomes that IL2RA induction be used routinely in first‐line therapy after kidney transplantation, with lymphocyte‐depleting induction reserved for high‐risk cases. These studies, however, mainly used outdated maintenance regimens. No large randomized trial has examined the effect of IL2RA or rATG induction versus no induction in patients receiving tacrolimus, mycophenolic acid and steroids. With this triple maintenance therapy, the addition of induction may achieve an absolute risk reduction for acute rejection of only 1–4% in standard‐risk patients without improving graft or patient survival. In contrast, rATG induction lowers the relative risk of acute rejection by almost 50% versus IL2RA in patients with high immunological risk. These recent data raise questions about the need for IL2RA in kidney transplantation, as it may no longer be beneficial in standard‐risk transplantation and may be inferior to rATG in high‐risk situations. Updated evidence‐based guidelines are necessary to support clinicians deciding whether and what induction therapy is required for their transplant patients today.     

Use of tacrolimus and mycophenolate mofetil as induction and maintenance in simultaneous pancreas‐kidney transplantation

Abstract Clinical trials using quadruple immunosuppression that include the combination of tacrolimus and mycophenolate mofetil have been shown to reduce the incidence of acute rejection episodes in simultaneous pancreas‐kidney (SPK) transplantation. In an attempt to obtain a low rejection rate without antibody induction therapy, we undertook a prospective study of combined tacrolimus and mycophenolate mofetil and steroids as primary immunosuppression for SPK transplantation. In this study, we analyzed 17 patients who received low‐dose intravenous tacrolimus as induction therapy. This was combined with oral tacrolimus, mycophenolate mofetil, and steroids as the primary immunosuppression regimen. There was a significant reduction of empirically and biopsy‐proven rejection with an incidence of 23 % (4 patients). Leukopenia, gastroparesis, and gastrointestinal side‐effects were the cause of discontinuation of mycophenolate mofetil, or low tacrolimus trough level in those patients who developed rejection. All rejection episodes were easy to treat, and none of them required antibody therapy. The combination of tacrolimus with mycophenolate mofetil without antibody induction therapy is effective in preventing early acute rejection. This combination is safe and effective as an alternative immunosuppressive regimen after SPK transplantation.     

肾移植术后应用达利珠单抗62例报告

目的评估达利珠单抗(抗CD25单克隆抗体)诱导治疗后的抗排斥反应疗效。方法对1999年9月～2004年4月间使用达利珠单抗的62例患者进行随访和统计。所有患者均在术中血管开放前1h应用达利珠单抗50mg，术后常规应用激素、环孢素A和霉酚酸酯。根据达利珠单抗的用量分为1剂组、2剂组和大于2剂组。结果随访时间最长达4年9个月，最短3个月。随访期间共发生急性排斥7例(11．3％)，最早1例发生在术后2个月，最晚为术后14个月，平均10．3个月；4例经过激素冲击治疗，完全逆转，2例部分逆转，仅1例发生于术后10个月的排斥，激素冲击治疗无效，术后第13个月移植肾失功而切除。结论应用达利珠单抗诱导治疗，肾移植术后急性排斥发生率降低，并使急性排斥发生时间推迟，程度减轻；可以安全、有效的减少环孢素的剂量。     

Pediatric liver transplantation with daclizumab induction

BACKGROUND: A new class of monoclonal antibodies (non-T-cell depleting) has gained favor for induction therapy after transplantation. This study evaluated the non-T-cell depleting antibody to the CD25 cell, daclizumab, as a single-dose induction agent immediately after pediatric liver transplantation to spare the use of the calcineurin inhibitor, tacrolimus, for 7 days in respect to both efficacy and renal function. METHODS: From January 1998 to November 2001, 81 pediatric orthotopic liver transplant recipients receiving 89 liver grafts were evaluated. The treatment arm (n=61) received daclizumab 1 mg/kg immediately after liver transplantation along with mycophenolate, steroids, and, on postoperative day 7, tacrolimus. The control group did not receive induction therapy, whereas tacrolimus, mycophenolate, and steroids were started immediately after surgery. RESULTS: The induction group had fewer patients with rejection within the first 30 days after liver transplantation (9 [14.8%] vs. 10 [50%]; P=0.003). The mean time to first rejection was similar between groups (12.1 [+/-7.8] days vs. 18.5 [+/-8.1] days; P=not significant). There was a 3.39 increase in relative risk to develop rejection within the first 30 days after orthotopic liver transplantation if the patient did not receive induction therapy (relative risk=3.39; 95% confidence interval [1.61, 7.14]). Two-year actuarial survival for the induction group was 93.2% compared with 85% in the control; graft survival was also similar between groups (87.8% vs. 72.7%) at 2 years. CONCLUSION: Daclizumab 1 mg/kg given immediately after pediatric liver transplantation and withholding tacrolimus, is safe, efficacious, and reduces rejections within the first 30 days after surgery.     

抗体诱导治疗在肝移植中的应用进展

应用生物蛋白制剂——抗体作为器官移植早期实施免疫抑制覆盖治疗的方法,可显著减少器官移植术后早期急性排斥反应的发生,且未显著增加移植后感染发生率,同时可延迟或减少CNI的应用,有利于保护肾功能、促进移植物功能恢复及受者长期存活。本文通过总结常见抗体免疫诱导剂的特点及作用机制,分析不同抗体诱导治疗应用于肝移植的临床获益与风险,为肝移植抗体诱导剂的合理使用提供参考。     

Steroid withdrawal or steroid avoidance in renal transplant recipients: focus on tacrolimus-based immunosuppressive regimens

Steroid-induced adverse effects after transplantation include cosmetic, metabolic, and cardiovascular complications. Steroid withdrawal or avoidance with cyclosporine-based regimens have been hampered by an unacceptably high rate of acute rejections and increased rates of graft loss. Recently the results of several large, randomized trials of steroid withdrawal/avoidance with tacrolimus-based immunosuppression in renal transplant recipients became available. A review of these trials appeared to be of clinical interest. Data from the THOMAS trial clearly indicate that steroid withdrawal from a regimen of tacrolimus, mycophenolate mofetil (MMF), steroids after 3 months after transplantation is safe with regard to acute rejection rate and graft survival. If an induction therapy with daclizumab is used in combination with tacrolimus and MMF (CARMEN trial), even steroid avoidance is safe with regard to acute rejection rate and graft survival. Finally, in the ATLAS trial, steroid avoidance with basiliximab in combination with tacrolimus (resulting in tacrolimus monotherapy) or alternatively with tacrolimus and MMF both resulted in similar graft survival, but higher rates of acute rejection. In conclusion, steroid withdrawal is safe from a triple-drug regimen of tacrolimus, MMF, and steroids after 3 months after transplantation, and steroid use may completely be avoided with tacrolimus, and MMF combined with daclizumab induction. Tacrolimus monotherapy may be achieved using basiliximab induction at the price of higher rates of acute rejection, but with unaffected graft survival. Thus tacrolimus-based immunosuppression with or without interleukin-2 receptor antagonist induction has made steroid withdrawal or avoidance a realistic option in renal transplantation.     

Daclizumab induction therapy associated with tacrolimus-MMF has better outcome compared with tacrolimus-MMF alone in pediatric living donor liver transplantation

AIMS: Immunosuppression therapy for the control of immunologic rejection is a key aspect in liver transplantation. The objective of this study was to evaluate induction therapy with daclizumab (DAC) in living donor liver transplantation (LDLT) in children. METHODS: We compared 2 different immunosuppression protocols in 30 children undergoing LDLT. The patients were divided into 2 groups: 12 patients received tacrolimus with mycophenolate mofetil (TAC-MMF), and 18 patients received tacrolimus with MMF and DAC induction therapy at days 0 and 14 after LDLT (DAC-TAC-MMF). Both groups were similar with regard to age, sex, weight, and indication for liver transplantation. The incidence of biopsy-proved rejection episodes, posttransplantation lymphoproliferative disease (PTLD), and renal dysfunction were evaluated. Tacrolimus levels at posttransplantation day 14 and at 2 months after transplantation were compared in the 2 groups. RESULTS: Acute rejection episodes were observed in 8 patients in the TAC-MMF group (66%), and none in the DAC-TAC-MMF group (0%; P < .05). Neither PTLD nor renal dysfunction was seen in any patient. Mean Tacrolimus level on posttransplantation day 14 was 10.67 +/- 5.4 ng/mL in the TAC-MMF group and 5.65 +/- 3.6 ng/mL in the DAC-TAC-MMF group (P < .05). After the second month the mean tacrolimus levels were 7.2 +/- 2.9 ng/mL and 6.8 +/- 3.5 ng/mL in the TAC-MMF and DAC-TAC-MMF groups, respectively. (P = NS). CONCLUSION: Induction therapy with DAC is safe and associated with a lower incidence of rejection episodes among children undergoing LDLT.     

Lung transplantation: a decade of experience.

BACKGROUND: Over the past 3 decades, the field of lung transplantation has been refined. However, many barriers exist that limit long-term success. The purpose of this study was to review a single institution's long-term experience with single and double lung transplantation and to assess the effect of different immunosuppressive therapies on outcomes. METHODS: Lung transplant recipients, both single and double, were reviewed, retrospectively. Patients were divided into five groups: group I, all lung transplants (n = 127); group II, single lung transplants (n = 73); group III, double lung transplants (n = 54); group IV, OKT3 induction therapy recipients (n = 27); and group V, RATG induction therapy recipients (n = 100). Rates of survival, rejection, bronchiolitis obliterans syndrome (BOS) and infection were analyzed at 1, 3, and 5 years. RESULTS: There were no significant differences in survival, acute rejection rate, freedom from BOS, nor infection between single and double lung transplant recipients. Induction therapy with RATG (group V) was associated with significantly improved survival and freedom from acute rejection, BOS, and infection when compared to OKT3 induction therapy (group IV). CONCLUSIONS: An earlier impression that RATG is superior to OKT3 induction therapy has borne true in terms of overall survival and incidence of BOS, acute rejection and infection rates. Lung transplantation, using RATG induction therapy, remains an important modality for end-stage pulmonary disease.     

Simultaneous kidney-pancreas transplantation without antilymphocyte induction

BACKGROUND: The introduction of potent new immunosuppressive agents may allow simultaneous kidney-pancreas transplantation to be performed without antilymphocyte induction. METHODS: We analyzed 30 simultaneous kidney-pancreas transplantations receiving tacrolimus, mycophenolate mofetil, and steroids without without antilymphocyte induction. Eighteen patients underwent pancreas transplantation with portal-enteric (P-E) drainage and the remaining 12 had systemic bladder (S-B) drainage. Target 12 hr trough tacrolimus levels for the first 3 months after simultaneous kidney-pancreas transplantation were 15-20 ng/ml. The oral mycophenolate mofetil dose was 2-3 g/day begun immediately posttransplant in two to four divided doses. Steroids were tapered according to protocol. RESULTS: All patients experienced immediate function of both kidney and pancreas grafts. One-year actuarial patient, kidney, and pancreas graft survival rates are 93, 93, and 90%, respectively. Nine patients (30%) had a total of 13 rejection episodes (12 biopsy proven) including 4 within 2 weeks, 6 between 2 weeks and 3 months, and 3 beyond 3 months after simultaneous kidney-pancreas transplantation. Three rejection episodes were treated with steroids alone and 10 were treated with antilymphocyte therapy (5 OKT3 and 5 ATGAM). A total of seven patients (23%) received antilymphocyte therapy. Three patients (10%) had more than one rejection episode. Two pancreas grafts (7%) and one kidney graft (3%) were lost from rejection. Four patients (13%) developed cytomegalovirus infection, but none had tissue-invasive cytomegalovirus. At present, 22 surviving patients (81%) remain on triple immunosuppression with tacrolimus, mycophenolate mofetil, and prednisone with excellent dual graft function. CONCLUSION: Tacrolimus, mycophenolate mofetil, and prednisone immunosuppression without without antilymphocyte induction is safe and effective after simultaneous kidney-pancreas transplantation.     

心脏移植术后的免疫抑制治疗和免疫监测

心脏移植是治疗终末期心脏疾病的有效手段。以钙调磷酸酶抑制剂(CsA或FK506)为基础的免疫抑制治疗是心脏移植术后最常用的免疫抑制方案,许多心脏移植受者在移植前或/和移植后同时使用单克隆抗体进行诱导治疗。雷帕霉素和Everolimus等新型免疫抑制剂在有效抑制急性排斥反应的同时还可预防移植物心血管病变,显示出较好的应用前景。应用免疫学指标、心肌标记物和其它血清标记物等相对无创的指标预测和估计排斥反应的发生及其程度,有助于尽早发现和控制移植排斥反应,以提高心脏移植的效果。