肾移植术后巨细胞病毒肺炎合并急性呼吸窘迫综合征32例临床分析

目的:总结肾移植术后巨细胞病毒(CMV)肺炎并发急性呼吸窘迫综合征(ARDS)患者的临床特点,为此类患者的进一步防治提供参考.方法:回顾近3年肾移植术后CMV肺炎并发ARDS的患者共32例,对其一般情况、治疗措施以及临床转归进行总结分析.结果:32例术后确诊CMV肺炎患者,均符合1992年美欧ARDS专题会议ARDS诊断标准,其中31例发生在术后2～4个月,16例曾发生过急性排斥反应(AR),14例因AR接受过激素冲击治疗,冲击治疗后CMV肺炎并发ARDS的发生率显著高于同期未冲击者.入院时外周血CD4 、CD8 细胞计数及其比值均显著降低.救治措施包括合理应用抗生素抗感染、撤减免疫抑制剂重建免疫功能、适时使用机械通气、支持治疗,并辅以连续性高容量血液滤过(CVVHF)治疗,治疗好转出院者20例,死亡12例,其中5例属于自动出院后死亡,2例死于肝功能衰竭,抢救成功率为62.50%.结论:肾移植术后CMV肺炎并发ARDS集中在术后2～4个月发病,因AR接受激素冲击治疗显著增加其发生率,此类患者救治困难,死亡率高,采用包括抗感染、重建免疫功能、适时机械通气、支持治疗以及CVVHF在内的综合治疗措施有助于提高患者的救治成功率.     

肾移植术后巨细胞病毒肺炎合并急性呼吸窘迫综合征临床及预后分析

目的分析肾移植术后巨细胞病毒(CMV)肺炎合并急性呼吸窘迫综合征(ARDS)的临床特点及预后因素,为其临床治疗及预后分析提供依据。方法采用病例-对照研究方法。收集广东药学院附属第一医院和中山大学附属第一医院1995年1月至2004年12月肾移植术后CMV肺炎合并ARDS完整病例资料55例,分为死亡组(31例)和生存组(24例),分析其临床表现。采用χ2检验或秩和检验进行死亡危险单因素分析,多因素Lo-gistic回归筛选预后因素。结果肾移植术后CMV肺炎合并ARDS病死率为56.4%,施行机械通气者病死率高达72.5%。统计分析显示,并发症数、X线胸片示肺浸润严重程度、机械通气是肾移植术后CMV肺炎合并ARDS死亡的独立危险因素(P<0.05),优势比(OR值)分别为2.60[95%可信区间(CI)1.00~6.76]、11.83[95%CI(1.14~123.07)]、19.32[95%CI(1.01~372.02)]。结论肾移植术后CMV肺炎合并ARDS具有极高的病死率,并发症数、X线胸片浸润严重程度、机械通气是肾移植术后CMV肺炎合并ARDS死亡的预后指标。减少肾移植术后CMV肺炎并发ARDS和死亡的主要措施在于移植术后预防性抗CMV治疗。     

连续性血液净化救治肾移植后重症巨细胞病毒肺炎

肾移植术后感染是危及患者生命的主要并发症，严重影响着肾移植患者的人／肾存活率。随着新型免疫抑制剂临床应用，移植后排斥反应的发生率不断下降。然而，感染，尤其是危及生命的严重肺部感染却有上升趋势。常见的严重感染有肾移植术后3个月左右的巨细胞病毒（CMV）肺炎，患者病情发展迅速，临床经过凶险，文献报道当合并成人急性呼吸窘迫综合征（ARDS）时，死亡率高达65％～90％。近年来，我们应用连续性血液净化（CBP）技术综合救治肾移植术后重症CMV肺炎合并ARDS患者，取得了较好的疗效，抢救成活率有了明显提高，使患者死亡率降低至20％。现将几点粗浅体会介绍如下。     

肾移植术后巨细胞病毒肺炎免疫抑制剂的应用研究简

目的 研究肾移植术后巨细胞病毒肺炎免疫抑制剂停用时机对患者预后的影响.方法 对82例肾移植术后巨细胞病毒肺炎患者根据从诊断巨细胞病毒肺炎到停用免疫抑制剂时间分成两组（≤3天组为早停组,＞3天为晚停组）,比较两组的预后及存活患者的病情控制时间.结果 两组患者的存活率及存活患者的病情控制时间均有显著统计学差异,早停组患者的存活率明显高于晚停组.结论 肾移植术后巨细胞病毒肺炎一经诊断在停用免疫抑制剂,同时使用小剂量糖皮质激素激素并予以抗病毒、抗感染、营养支持等综合治疗是成功治疗肾移植术后巨细胞病毒肺炎的关键.巨细胞病毒是肾移植术后肺部感染的常见病原体之一,79%发生在肾移植术后3-6个月内,其病情复杂,死亡率高,医疗费用高,成为临床治疗的难点.但近年来,随着救治病例的增多,治疗水平的不断进步,肾移植术后巨细胞病毒肺部感染的治愈率也提高.如何成功救治肺部感染.不同文献对肾移植术后巨细胞病毒肺炎免疫抑制剂停用或减量的时机有不同的报道.现将同济医院2002-2010年呼吸内科救治的82例肾移植术后巨细胞病毒肺炎患者病例进行分析,探讨免疫抑制剂的调整时机对患者预后、存活患者的病情控制的时间.     

肾移植术后巨细胞病毒肺炎免疫抑制剂的应用研究

目的研究肾移植术后巨细胞病毒肺炎免疫抑制剂停用时机对患者预后的影响。方法对82例肾移植术后巨细胞病毒肺炎患者根据从诊断巨细胞病毒肺炎到停用免疫抑制剂时间分成两组(≤3天组为早停组,3天为晚停组),比较两组的预后及存活患者的病情控制时间。结果两组患者的存活率及存活患者的病情控制时间均有显著统计学差异,早停组患者的存活率明显高于晚停组。结论肾移植术后巨细胞病毒肺炎一经诊断在停用免疫抑制剂,同时使用小剂量糖皮质激素激素并予以抗病毒、抗感染、营养支持等综合治疗是成功治疗肾移植术后巨细胞病毒肺炎的关键。     

肾移植术后巨细胞病毒感染的机械通气治疗观察

巨细胞病毒肺炎是肾移植术后全身感染的重症之一，及时采用呼吸机辅助通气等综合治疗措施可改善预后．肾移植术后由于应用大剂量免疫抑制剂，机体细胞免疫和体液免疫功能均显著减弱，易并发多个脏器的感染，如肺炎，肝炎，胰腺炎，脑膜炎。其中尤以巨细胞肺炎是肾移植术后的严重并发症之一，是造成肾移植术后死亡的主要原因，死亡率高达25％。总结我院2000—2005年肾移植术后合并巨细胞肺炎的9例患者，旨在引起对此病的足够重视，总结经验。     

肾移植术后空腹血糖变化规律及其对预后的影响分析

目的 探讨肾移植术后存活1年以上患者空腹血糖变化规律及其对预后的影响.方法 收集446例1993年1月至2008年12月接受肾移植手术且移植肾存活1年以上患者的临床资料,根据术前空腹血糖,将患者分为移植前糖尿病、空腹血糖受损、空腹血糖正常3组,观察各组术后空腹血糖变化规律.对428例术前非糖尿病患者,根据空腹血糖分析术后移植后糖尿病( PTDM)发生及转归,比较持续性PTDM和一过性PTDM临床特点,并比较PTDM组和非PTDM组术后并发症及生存率的差异.结果 肾移植后患者血糖整体呈先升高后下降的趋势.428例术前非糖尿病患者,共有87例(20.3％)发生PTDM,其中15例(占总PTDM的17.2％)在随访中转为空腹血糖正常或空腹血糖受损.与持续性PTDM相比,一过性PTDM患者急性排斥反应发生率更高(P=0.043).与非PTDM组相比,PTDM组术后感染、高血压和脂代谢紊乱发生率更高(P＜0.05).平均随访(5.65±3.68)年,两组患者生存率和生存时间未见明显差异.结论 PTDM并非持续存在,在病程中有可能转为空腹血糖受损或空腹血糖正常.急性排斥反应是一过性血糖升高的危险因素.肾移植后PTDM患者术后更容易发生感染、高血压、高血脂等并发症,但本组术后随访,存活率未受明显影响.     

雷公藤多苷片在肾移植术后早期抗排斥中的作用

目的探讨肾移植术后围术期及术后6个月应用雷公藤(TW)多苷的临床效果。方法对80例同期肾移植受者进行对照性临床研究,随机分为TW组和未应用TW环孢素(Cs A)组各40例。患者术后给予Cs A、吗替麦考酚酯及激素三联免疫抑制疗法。观察患者围术期及术后6个月排斥反应发生情况。结果肾移植术后应用TW可以明显降低肾移植术后早期急性排斥发生率,加快患者肌酐恢复至正常的速度,同时降低术后6个月急性排斥反应发生率。结论 TW多苷片可降肾移植早期急性排斥反应发生率,加快患者恢复速度。     

肾移植术后细菌性肺部感染

肾移植术后细菌感染是常见和棘手的问题,而肺部感染是引起肾移植术后患者死亡的主要原因之一［１］。国外报导肾移植后肺部感染主要是卡氏肺囊虫肺炎（ＰＣＰ）、巨细胞病毒肺炎（ＣＭＶ）、肺结核、肺霉菌病等机会性感染,对于肺部细菌感染报导较少。总结我院１９７８年至１９９６年肾移植手术１０５６例患者中细菌性肺炎或细菌性肺炎合并霉菌,细菌性肺炎合并结核,合并巨细胞病毒感染等患者５１例,报告如下。１临床资料１．１一般资料：５１例患者,男性３３例,女性１８例,年龄１６～６２岁,平均４１．２７±１１．１４岁。其中慢性…     

肾移植术后巨细胞病毒肺炎的临床研究

目的:探讨肾移植术后巨细胞病毒(CMV)肺炎的临床特点及诊疗对策。方法:回顾34例肾移植术后CMV肺炎患者临床资料,总结临床特点和治疗措施。结果:34例患者,治愈30例,占88.24%,死亡4例(其中放弃治疗后死亡2例)。治愈患者除1例出现移植肾排斥反应外,其余功能均正常。高剂量更昔洛韦联用糖皮质激素组,在需使用呼吸机几率和死亡率方面均低于未使用糖皮质激素的常规剂量更昔洛韦组(P=0.045和0.010)。结论:早期及时诊断,适时适量应用激素,足剂量长疗程抗病毒治疗,及早进行高流量给氧或辅助呼吸等综合治疗是提高治愈率、降低病死率的关键。     

Immunosuppression and metabolic syndrome in renal transplant recipients

Cardiovascular disease is the major cause of death in renal transplant recipients. Renal transplant recipients share the same cardiovascular risk factors as the general population, including hypertension, hyperlipidemia, diabetes mellitus, smoking, and positive family history. However, renal transplant recipients are also exposed to transplant-specific risk factors such as chronic immunosuppression. Most renal transplant recipients receive combinations or permutations of immunosuppressive drugs including a calcineurin inhibitor (cyclosporine or tacrolimus), a mammalian target of rapamycin (mTOR) inhibitor (sirolimus), an antiproliferative drug (mycophenolate mofetil and azathioprine), and corticosteroids. Cyclosporine and tacrolimus can induce glucose intolerance, hypertension, and hyperlipidemia. Sirolimus can induce hyperlipidemia. Corticosteroids can induce glucose intolerance, hypertension, hyperlipidemia, and weight gain. Central to the development of metabolic complications in renal transplant recipients is insulin resistance induced by immunosuppressive drugs. Insulin resistance is considered to be the central pathophysiological feature of metabolic syndrome, which is linked to increased risk of cardiovascular disease and to chronic renal failure. Therefore, metabolic syndrome likely contributes to cardiovascular disease and chronic renal allograft dysfunction in renal transplant recipients. Treatment of metabolic complications in renal transplant recipients is difficult, as conversion to an alternate immunosuppressive drug may lead to introduction of new metabolic complications, and as discontinuation of immunosuppressive therapy may lead to rejection. Future research should focus on designing immunosuppressive regimens that have minimal effects on insulin resistance and metabolic complications but that are effective in preventing acute rejection and in prolonging both allograft and patient survival.     

Risk factors for accelerated atherosclerosis in renal transplant recipients

The factors responsible for atherosclerosis in renal transplant recipients are not known. In the present study, cardiovascular disease was investigated in 403 patients who received 464 kidney transplants during a 10-year period. Among those who had no clinical evidence of vascular disease at the time of transplantation, atherosclerotic complications developed in 15.8 percent during the post-transplant follow-up period (46.1 +/- 36.2 months). Pre- and post-transplant vascular diseases were closely linked. However, after taking pre-transplant vascular disease into account, multivariate analysis showed that a number of known risk factors (age, sex, diabetes, cigarette smoking, hypertension, and serum cholesterol) were independently associated with post-transplant vascular disease. In addition, the number of acute rejection episodes (all treated with high doses of corticosteroids) was also independently linked to vascular disease. These results suggest that an increased prevalence of known risk factors, and events linked to allograft rejection, explain the high incidence of cardiovascular disease in renal transplant recipients.     

The role of transbronchial lung biopsy in the treatment of lung transplant recipients. An analysis of 200 consecutive procedures.

STUDY OBJECTIVE: The purposes of this study were as follows: (1) to establish the positivity rate and complication rate of transbronchial lung biopsies in the treatment of lung transplant recipients; (2) to determine the sensitivity of transbronchial lung biopsy specimens for the diagnosis of clinically suspected acute rejection and cytomegalovirus pneumonia; and (3) to examine the results of surveillance transbronchial lung biopsies in clinically and physiologically stable recipients. DESIGN: Retrospective review and analysis of 203 consecutive procedures. SETTING: Washington University Lung Transplantation Program, Washington University School of Medicine and Barnes Hospital, St. Louis, Mo. PATIENTS: Fifty-five lung transplant recipients. INTERVENTIONS: Biopsies were done with 2-mm fenestrated forceps using fluoroscopic guidance. Two hundred three bronchoscopies with transbronchial lung biopsy were performed for clinical indications (n = 88), routine surveillance (n = 90), or follow-up of a previous biopsy (n = 25). Biopsy specimens showing acute allograft rejection were classified according to the scheme recommended by the Lung Rejection Study Group. MEASUREMENTS AND RESULTS: The positivity rate and complication rate were determined for the procedures. In procedures performed for clinical indications, the sensitivity for the diagnosis of acute rejection and cytomegalovirus pneumonia was calculated by a decision-to-treat analysis. A specific histologic diagnosis was detected in 69 percent of the clinical procedures, 57 percent of the surveillance procedures, and 64 percent of the follow-up procedures. For clinical indications, the sensitivity of transbronchial lung biopsy was 72 percent for the diagnosis of acute rejection and 91 percent for the diagnosis of cytomegalovirus pneumonia. Surveillance biopsy specimens often showed clinically inapparent rejection or cytomegalovirus pneumonia. The overall complication rate was 8.9 percent; none of the complications were life threatening. CONCLUSIONS: Transbronchial lung biopsy is a useful and safe procedure in the treatment of lung transplant recipients. When performed for clinical indications, the procedure proved to be sensitive for the diagnosis of acute rejection and cytomegalovirus pneumonia. When performed for surveillance in clinically and physiologically stable recipients, the incidence of rejection and cytomegalovirus pneumonia was unexpectedly high; the potential clinical implications of these findings will require further study.     

Bacterial pneumonia in solid organ transplantation

Approximately 4% of recipients of solid organ transplants in the United States develop bacterial pneumonia in the posttransplant period, often in the first 3 months following transplantation. The incidence of bacterial pneumonia is highest in recipients of heartlung (22%) and liver transplants (17%), intermediate in recipients of heart transplants (5%), and lowest in renal transplant patients (1 to 2%). The crude mortality of bacterial pneumonia in solid organ transplantation has exceeded 40% in most series. Beyond those risk factors identified for nosocomial pneumonia, the occurrence of primary cytomegalovirus (CMV) infection, graft rejection, maintenance antirejection therapy with prednisone, azathioprine, and antilymphocyte globulin, antirejection therapy with high-dose corticosteroids or OKT3 and splenectomy have been associated with a significantly increased risk of bacterial pneumonia in these patients. In the first 3 months posttransplant, gram-negative bacilli, Staphylococcus aureus and Legionella predominate and mortality is very high, in excess of 60%. Thereafter, bacterial pneumonias are caused primarily by Streptococcus pneumoniae and Hemophilus influenzae, with considerably lower mortality. Bacterial pneumonia must be suspected in any transplant patient presenting with fever and cough, especially associated with dyspnea or infiltrates on chest radiograph. If large numbers of bacteria and polymorphonuclear leukocytes are not visualized in respiratory secretions the work-up should proceed directly to fiberoptic bronchoscopy with bronchoalveolar lavage and/or protected brush specimen to establish the microbiologic diagnosis as accurately as possible. For presumptive gram-negative bacillary pneumonia, the initial regimen must be effective against Pseudomonas aeruginosa. Prevention of bacterial pneumonia in transplant patients must begin with immunization against S pneumoniae and Influenza A, and include precautions taken to prevent nosocomial pneumonia. It further may include measures to prevent CMV infection and the use of trimethoprim/sulfamethoxazole prophylaxis during the first year posttransplantation. Ultimately, novel technologies such as selective antimicrobial decontamination and/or protective isolation during the early postoperative period may prove effective.     

New trends in combined transplantation of the heart and lungs

Heart-lung transplantation is a surgical alternative for patients with end-stage lung disease with associated right heart failure. While the procedure is very promising, the morbidity and mortality remain high. The current understanding of the proper selection of candidates, procurement and preservation of donor organs, operative procedure and postoperative care continues to evolve. At the University of Pittsburgh, 70 heart-lung transplantations have been performed since 1982. Early infection and chronic rejection are the major factors influencing survival. Early (less than 2 weeks) intrathoracic infection occurred in 43% of heart-lung transplant recipients, with pneumonia being the most frequent infection. The incidence of pneumonia in heart-lung transplant recipients is twice that in a comparable group of heart recipients. Subclinical pneumonitis in the donor lung, abnormal muco-ciliary clearance and altered allogenic response in the transplanted lung are significant factors associated with the increased incidence of early infections. Chronic rejection, manifested as bronchiolitis obliterans, has occurred in 54% of heart-lung transplantation recipients. Infection caused by cytomegalovirus, Epstein-Barr virus and Pneumocystis carinii have been shown to increase the incidence of bronchiolitis obliterans, as have episodes of acute rejection. Recent reports of a 61% 2-year survival rate represent a substantial improvement over earlier trials. With a better understanding of the pathogenesis of infection in the transplanted lung as well as improved immunosuppressive agents, further improvements in survival can be expected.     

肾小球疾病患者糖代谢改变相关因素探讨

目的探讨肾小球疾病患者糖代谢异常的患病状况及其危险因素。方法选取无糖尿病史、初治的肾小球疾病患者1885例。监测血糖或OGTT,并收集临床、病理及化验资料进行统计学分析和比较。结果（1）T2DM患病率15．3％,糖调节异常（IGR）26．6％。若单纯检测FPG将漏诊全部IGR的72．9％及全部T2DM中的61．5％;（2）糖代谢异常的患病率随着增龄和肾功能下降而升高（P〈0．01）;有DM家族史、伴高血压、肥胖、高尿酸或高甘油三酯血症者糖代谢异常患病率均明显升高（P〈0．05）;（3）糖代谢异常组肾内小血管病变、小管间质病变及肾小球硬化发生率均明显增加（P〈0．05）;（4）Logistic回归分析显示,年龄（0R=3．156）、BMI、T2DM家族史（OR=1．334和2．541）、伴高血压、高甘油三酯血症（OR=1．587和1．669）、肾功能异常是糖代谢异常的高危因素。结论无糖尿病史的肾小球疾病患者中糖代谢异常患病率41．9％,其相关因素包括年龄、DM家族史、伴高血压、肥胖、高尿酸和（或）高甘油三酯血症。     

Challenges in the diagnosis and management of new-onset diabetes after transplantation

With the availability of newer and more potent immunosuppressive agents, post-transplant survival has markedly improved. However, these agents, together with the rising age of transplant recipients, have been associated with a rise in the incidence of new-onset diabetes after transplantation (NODAT). Besides the traditional risk factors for diabetes mellitus, such as age, obesity, hypertension, and family history of diabetes, additional risk factors for NODAT are identified. These include immunosuppressive therapy, hepatitis C infection, acute rejection, and deceased donor kidney transplant. In this article, we discuss the epidemiology, risk factors, pathophysiology, clinical course, and therapeutic and diagnostic challenges of this emerging disease.     

甲基强的松龙治疗肾移植术后巨细胞病毒肺炎时体温变化与预后的关系

目的探讨甲基强的松龙治疗肾移植术后巨细胞病毒肺炎时患者体温变化与预后的关系。方法选择符合巨细胞病毒肺炎诊断标准的肾移植术后患者97例,根据使用甲基强的松龙72小时后患者体温变化情况分为体温正常组和发热组,比较两组患者的预后情况。结果发热组患者入住ICU人数及入住时间显著高于体温正常组（P〈0．05）,多器官功能障碍综合征和急性呼吸窘迫综合征的发生率显著高于体温正常组（P〈0．05）,进展为多器官功能障碍综合征、急性呼吸窘迫综合征的时间显著快于体温正常组（P〈0．05）,机械通气的发生率及带机时间、住院时间、死亡率均显著高于体温正常组（P〈0．05）。结论甲基强的松龙治疗肾移植术后巨细胞病毒肺炎患者的体温变化可以反映患者的预后情况。     

Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis

M.G.J. de Boer, F.P. Kroon, S. le Cessie, J.W. de Fijter, J.T. van Dissel. Risk factors for Pneumocystis jirovecii pneumonia in kidney transplant recipients and appraisal of strategies for selective use of chemoprophylaxis.
Transpl Infect Dis 2011: 13: 559–569. All rights reserved Abstract: Risk stratification‐based duration of trimethoprim‐sulfamethoxazole (TMP‐SMX) chemoprophylaxis to prevent Pneumocystis pneumonia (PCP) in kidney transplant recipients is not a universally adapted strategy and supporting evidence‐based sources are limited. We performed a large retrospective study to identify risk factors for PCP in kidney transplant recipients and to define parameters for use in clinical prophylaxis guidelines. Fifty consecutive patients with confirmed PCP and 2 time‐matched controls per case were enrolled. All patients were participants of the kidney transplantation program of the Leiden University Medical Center, a tertiary care hospital in the Netherlands. Potential risk factors were compared between groups by uni‐ and multivariate matched analyses. At transplantation, age >55 years (adjusted odds ratio [OR] 2.7, 95% confidence interval [CI] 1.3–5.9) and not receiving basiliximab induction therapy (adjusted OR 4.3, 95% CI 1.1–17.1) predicted development of PCP. In the final multivariate analysis, only cytomegalovirus infection (adjusted OR 3.0, 95% CI 1.2–7.9) and rejection treatment (adjusted OR 5.8, 95% CI 1.9–18) were found to be independently associated with PCP. Using the variables identified by the multivariate analyses, effects of different hypothetical chemoprophylaxis strategies were systematically evaluated. Exploring different scenarios showed that chemoprophylaxis in the first 6 months for all renal transplant patients – and during the first year posttransplantation for patients >55 years of age or those treated for rejection – would result in very low PCP incidence and optimal avoidance of TMP‐SMX toxicity. The results provide a rationale for further prospective study on targeted provision of chemoprophylaxis to prevent PCP in kidney transplant patients.