小肠移植术后巨细胞病毒感染二例的治疗体会

目的 总结小肠移植术后巨细胞病毒(CMV)感染的治疗经验.方法 1994年至2009年间完成15例小肠移植,分为3个阶段:1994-1995年为第1阶段(3例),2003-2006年为第2阶段(7例),2007年以后为第3阶段(5例).第1阶段术后未进行CMV感染的预防;第2阶段通过肠镜、病理检查和血清学检查(CMV IgM、CMV pp65和CMV DNA)进行CMV感染的诊断,术后静脉注射更昔洛韦2~3周,口服阿昔洛韦3个月以预防CMV感染;第3阶段在第2阶段的基础上,应用实时定量PCR技术检测CMV DNA,并制定计划性监测方案,术后静脉注射更昔洛韦2~3周,口服更昔洛韦3个月预防CMV感染,采用CMV感染的抢先治疗方案.结果 15例患者中有2例(13.3 %)术后发生CMV感染.其中第2阶段1例术后45 d发生移植肠CMV肠炎,术后64 d并发CMV肺炎,应用更昔洛韦和胸腺肽,并停用他克莫司,最终转为重度排斥反应后死亡;第3阶段1例术后第3个月发生CMV感染,经CMV抢先治疗后治愈.结论 小肠移植术后应进行CMV的预防性治疗,严密监测CMV血清学指标,适时进行抢先治疗.对于CMV侵袭性疾病在进行有效治疗的同时应注意排斥反应的发生.

Abstract：

Objective Cytomegalovirus (CMV) has remained the most significant pathogen that threatens the outcome of small bowel transplantation (SBTx). This paper To outline preliminary experience of prophylaxis and treatment of cytomegalovirus (CMV) in 15 cases subject to small bowel transplantation (SBTx) and also review current progress of diagnosis and treatment of CMV.Methods Fifteen cases of SBTx were divided into 3 eras: era Ⅰ (1994-1995)-3 SBTx treated with cyclosporine-based immunosuppression; era Ⅱ (2003-2006)-7 SBTx treated with tacrolimus-based immunosuppression; and era Ⅲ (2007-present)-5 SBTx treated with Alemtuzumab induction therapy and maintenance tacrolimus monotherapy. No antiviral prophylaxis after SBTx was applied during era Ⅰ; in era Ⅱ, ileoscopic and pathological diagnosis of CMV graft enteritis was defined, and plasma diagnosis tools including CMV-IgM, CMV pp65 and CMV DNA with PCR were introduced. 2-3 weeks intravenous ganciclovir prophylaxis of CMV was underway, followed by 3 months oral acyclovir; In era Ⅲ, more precise real-time PCR technique was used to detect CMV DNA copies, and the schedule of the CMV surveillance was set up, antiviral prophylaxis therapy was modified to 2-3 weeks intravenous ganciclovir and 3 months oral ganciclovir, and preemptive therapy to halt the progression of asymptomatic infection to clinical disease was also introduced.Results Two of 15 SBTx recipients suffered from CMV with the occurrence rate of 13.3%. One recipient in era Ⅱ suffered from CMV graft enteritis on postoperative day 45, and CMV pneumonia on postoperative day 64, he received intravenous ganciclovir and thymus peptide, paused tacrolimus maintenance, and finally he died from severe acute cellular rejection. 94 100 copies/ml of CMV DNA in periphery blood of a recipient in era Ⅲ was detected with real-time PCR at 3rd month after SBTx, and a preemptive therapy successfully halted the CMV infection.Conclusion Antiviral prophylaxis therapy and close surveillance of CMV infection after SBTx should be performed, and preemptive therapy can also halt the CMV infection. When CMV disease occurs, the recipient should receive effective antiviral therapy, and acute cellular rejection also should be closely monitored at same time.     

Early detection of primary cytomegalovirus infection after heart and kidney transplantation and the influence of hyperimmune globulin prophylaxis

A randomized study of prophylaxis with hyper-immune globulin (HIg) was performed in 28 cytomegalovirus (CMV)-seronegative heart and kidney recipients with CMV-seropositive donors who were extensively monitored for active CMV infection and CMV disease. Detection of CMV antigen in peripheral blood granulocytes (antigenemia) was the first sign of primary CMV infection, generally occurring several weeks before IgM or IgG anti-CMV antibodies were detected and before positive cultures appeared. A correlation was found between rejection treatment with OKT3 or ATG, severity of CMV disease, and graft loss. Rejection treatment had no influence on incidence of CMV transmission. Primary CMV infection occurred most often in older patients with older donors. No beneficial effects were seen with HIg prophylaxis, which was administered from week 1 until week 7 after transplantation. Incidence of primary CMV infection was equal in both groups (50%) and no influence on the severity of primary CMV infection was seen. The only effect that was seen was on the time from transplantation to detection of active CMV infection, which was prolonged by HIg prophylaxis.     

Cytomegalovirus infection after organ transplantation: an update with special emphasis on renal transplantation

Abstract. Cytomegalovirus infections are still the most important infectious complications after organ transplantation. Besides historical notes this review will deal with new aspects concerning the epidemiology of the CMV, diagnostic modalities of CMV infection, the delicate counterbalance between the immune system and the CMV, as well as the symptomatology of this infection. Furthermore, aspects like prophylaxis and new, promising therapeutic regimes for treatment of infection will be dealt with. Although this update is applicable for all types of solid organ transplantation, emphasis will be on renal transplantation.     

Cytomegalovirus infection after organ transplantation: an update with special emphasis on renal transplantation

Cytomegalovirus infections are still the most important infectious complications after organ transplantation. Besides historical notes this review will deal with new aspects concerning the epidemiology of the CMV, diagnostic modalities of CMV infection, the delicate counterbalance between the immune system and the CMV, as well as the symptomatology of this infection. Furthermore, aspects like prophylaxis and new, promising therapeutic regimes for treatment of infection will be dealt with. Although this update is applicable for all types of solid organ transplantation, emphasis will be on renal transplantation.     

肝移植术后巨细胞病毒感染的防治研究

目的探讨肝移植患者术后巨细胞病毒 (CMV)感染情况及其与急性排斥反应的关系。方法应用PCR和ELISA方法检测 78例肝移植受体手术前后、78例供体及 70例接受上腹部手术的非肿瘤患者血清中的CMV DNA和CMV抗体 ,用免疫组织化学方法检测肝组织中CMV抗原。结果供、受体术中肝脏活体组织学检查的CMV早期抗原 (EA)和晚期抗原 (LA)全部为阴性。术前CMV DNA或CMV IgM阳性的受体术后均为阳性 ;术前CMV DNA或CMV IgM阴性的受体术后CMV DNA或CMV IgM转为阳性的分别有 2 6 %和 10 %。 78例受体CMV DNA阳性率由术前的 5 %增加到术后的 31% ,两者比较差异有显著意义 (P <0 0 5 )。 2 6例患者发生了 33次急性排斥反应 ,16次 (49% )CMV DNA检测阳性、11次 (33% )CMV IgM检测阳性 ,而在术后常规检测血CMV DNA和CMV IgM的阳性率分别不超过 13%和 9% ,两者比较差异有显著意义 (P <0 0 5 )。 2 6例发生急性排斥患者肝脏活体组织学检查CMV EA和CMV LA阳性者均为 9例 (2 7% ) ,与术后的常规肝脏穿刺结果比较差异有显著意义 (P <0 0 5 )。结论 1.肝移植术后CMV感染率明显升高。 2 .CMV感染可能是发生急性排斥反应的危险因素。 3.发生急性排斥反应时 ,应使用抗CMV药物 ;未感染CMV的受体接受感染供体的肝脏时应预防用药。     

肾移植后并发巨细胞病毒肺炎与十二指肠出血(附1例报告并文献复习)

目的:探讨肾移植术后并发巨细胞病毒感染与上消化道出血的临床特征。方法:回顾性分析1例患者于肾移植术后并发巨细胞肺炎同时并发严重十二指肠降部出血的临床资料,并复习有关文献,总结其诊治经验。结果:经紧急行消化道血管造影及栓塞止血后,患者平稳度过危险期,痊愈。结论:肾移植术后合并巨细胞病毒感染与上消化道出血的死亡率高,及时有效的诊治可挽救患者生命,多学科共同协作能取得良好治疗效果。     

Ganciclovir therapy of symptomatic cytomegalovirus infection in renal transplant recipients

We used ganciclovir to treat 11 renal transplant recipients with symptomatic cytomegalovirus infection (seven primary), including one severe, five mild and five moderate cases. Two patients exhibited a non-mechanically ventilated pneumonitis and two others a gastrointestinal involvement. Ganciclovir was used intravenously according to a schedule which took into account renal function, for a median time of 14 days. All patients survived. Cytomegalovirus infection was cured in all patients but two: in the first an early clinical relapse required a second successful ganciclovir course; in the other graftectomy was needed to control infection. Graft was lost in an additional cured patient. Ganciclovir was well tolerated, especially with regard to haematological status. At the current follow-up of at least one month after the end of ganciclovir therapy, no further clinical relapse was observed; however, in one clinically cured patient cytomegalovirus was isolated from blood one week after ganciclovir cessation. These encouraging preliminary data suggest that ganciclovir therapy should be started as soon as cytomegalovirus infection is suspected, especially in cytomegalovirus seronegative recipients receiving a seropositive graft.     

The impact of donor cytokine gene polymorphisms on the incidence of cytomegalovirus infection after kidney transplantation

Cytomegalovirus (CMV) seronegative recipients of kidneys from CMV seropositive donors are at a high risk of CMV infection after transplantation since viruses in the allograft may reactivate in patients without prior immunity. We hypothesized that the genetic background of the graft has an influence on the incidence of infection. Effects of IL10, IL6 and IFNG gene polymorphisms, known to affect CMV infectivity, were investigated in 71 CMV seronegative recipients of grafts from CMV seropositive cadaver donors. Donor IL10(-1082 AA) genotype reduced the incidence of CMV infection (p=0.031) and CMV episodes in these patients tended to occur later (AA: median 83 days, AG/GG: median 45 days, p=0.072). In multivariate analysis, other explaining factors than the donor IL10(-1082 AA) genotype alone did not improve Cox hazard model (HR=0.3, 95% CI=0.09-0.96, p=0.043). Recipient polymorphisms did not reduce the incidence of CMV infection. We conclude that donor IL10 gene polymorphisms may influence the likelihood of CMV infection in the high risk patients investigated.     

HLA-G与肾移植术后巨细胞病毒活动性感染的相关性研究

目的 研究HLA-G与肾移植术后巨细胞病毒(CMV)活动性感染的相关性,分析其作用机制及意义。方法 初次肾移植受者215例,按照术后是否发生CMV活动性感染将受者分为CMV阳性组和CMV阴性组,采用流式细胞术检测膜结合型HLA-G1 (mHLA-G1)的表达,采用酶联免疫吸附试验检测可溶性HLA-G5 (sHLA-G5)的表达,采用逆转录聚合酶链法检测HLA-G mRNA的表达,采用蛋白质印迹法验证sHLA-G5的表达,采用免疫组织化学法和HE染色观察移植肾组织中HLA-G的表达,采用ROC曲线分析sHLA-G5水平预测CMV活动性感染的Cutoff值。结果 术前两组间HLA-G表达的差异无统计学意义(P＞0.05)。术后两组间外周血淋巴细胞表面mHLA-G1均呈低表达,CMV pp65阳性时亦无明显变化。CMV阳性组外周血中CD14+ mHLA-G1+细胞显著升高(P＜0.05),达到(45.53±17.32)％,转阴后下降至(10.22±5.78)％。CMV阳性组外周血中sHLA-G5表达水平明显升高(P＜0.05),其预测CMV活动性感染的最适Cutoff值为202.9μg/L,具有很高的诊断准确性。CMV阳性组受者外周血中HLA-G mRNA的表达水平均显著高于CMV阴性组(P＜0.05)。12例CMV活动性感染受者移植肾活检样本中,10例肾小管上皮细胞HLA-G表达呈阳性。结论 HLA-G在外周血中的表达显著升高和移植肾肾小管上皮细胞的阳性表达可能是保护移植肾功能的机制之一。以sHLA-G5表达水平202.9μg/L作为Cutoff阈值,具有很好的判断CMV活动性感染的价值。     

Cytomegalovirus pneumonitis after kidney transplantation is not caused by plugging of cytomegalic endothelial cells only

In addition to life-threatening pneumonia, cytomegalovirus (CMV) may also cause subclinical pulmonary dysfunction after kidney transplantation. To investigate the role of plugging of cytomegalic endothelial cells in the pulmonary capillary bed, we prospectively determined specific carbon monoxide diffusion capacity (KCOc) and its components: the pulmonary diffusing membrane factor (Dm) and pulmonary capillary blood volume (Vcap) before and during CMV infection in 13 kidney transplant recipients and 13 controls. During CMV infection, mean KCOc decreased significantly by 28 % of the initial value (mean KCOc 79 vs 109; P < 0.005 ) due to a decrease in both Vcap and Dm. The KCOc in controls showed a significantly smaller decrease due to a slightly lower Vcap. We conclude that kidney transplant recipients with CMV infection have significant pulmonary diffusion disturbances due to a combination of lower Vcap and lower Dm. The most likely explanation for this phenomenon is a local inflammatory process due to CMV and not plugging of cytomegalic endothelial cells only. Received: 25 February 1998 Received after revision: 26 June 1998 Accepted: 22 September 1998     

HLA-G与肾移植术后急性排斥反应和巨细胞病毒活动性感染的相关性研究

目的 探讨HLA-G的表达水平与肾移植术后急性排斥反应(AR)和巨细胞病毒(CMV)活动性感染的相关性.方法 根据术后是否发生AR或CMV活动性感染,将132例初次肾移植受者分为肾功能稳定组、AR组和CMV组.另选择41例健康供者作为对照组.采用流式细胞术、酶联免疫吸附试验、蛋白质印迹法以及实时定量聚合酶链法检测各组HLA-G及其mRNA的表达,并采用免疫组织化学法观察移植肾组织中HLA-G的表达.结果 肾移植前后各组膜结合型HLA-G1 (mHLA-G1)的表达均处于较低水平,仅术后CMV组mHLA-G1+的中性粒细胞出现显著升高(P＜0.05).术前可溶性HLA-G5(sHLA-G5)的表达水平肾功能稳定组显著高于对照组(P＜0.05);术后sHLA-G5的表达水平CMV组显著高于肾功能稳定组(P＜0.05),而肾功能稳定组均高于对照组和AR组(P＜0.05),AR组与对照组的差异无统计学意义(P＞0.05).术后CMV组sHLA-G5 mRNA的表达水平最高(P＜0.05),肾功能稳定组次之,对照组和AR组均较低.21例AR组移植肾组织活检样本中,17例HLA-G表达呈阴性,3例呈阳性,1例呈弱阳性;9例CMV组移植肾组织活检样本的HLA-G表达均为阳性.132例受者中,28例CMV感染者的AR发生率为7.1％(2/28),104例非CMV感染者的AR发生率为25.0％(26/104),二者间AR发生率的差异有统计学意义(P＜0.05).结论 sHLA-G5可作为预测AR和CMV感染的生物标志分子;CMV感染和AR与受者体内的免疫平衡状况相关.     

Cytomegalovirus (CMV) excretion as a factor in the severity of CMV disease in kidney and simultaneous kidney and pancreas transplantation

The aim of the study was to evaluate the virological parameters associated with the severity of cytomegalovirus (CMV) disease in renal and simultaneous renal and pancreatic transplantation. The association of the viral profile and the severity of the viral disease was analysed taking into account different confounding variables susceptible to linkage with the severity of the CMV infection and the viral parameters. All the patients transplanted between 1 January 1989 and 31 December 1990, a total of 242, were prospectively followed by viral cultures in blood and urine and by serological methods using the detection of CMV-specific IgM and the complement fixation (CF) test. The samples were taken systematically each week for the first month and then at day 90, 180 and every 6 months and also in cases of clinical manifestations related to viral disease. CMV infection was diagnosed virologically by the presence of viraemia, viruria, IgM, or a significant rise in CMV antibody titre in CF. CMV disease was classified as asymptomatic, mild (fever and/or leukopenia), moderate (fever, leukopenia and liver abnormalities), severe (CMV pneumopathy and/or gastrointestinal disease) or fatal. The incidence of CMV infection was 65% (157/242): 32% asymptomatic, 36% mild, 30% moderate and 2% severe. The presence of IgM was associated with the severity of CMV disease: 51.4% of moderate and severe CMV infections in the group with IgM versus only 16% in the group without IgM (P < 0.0001). The risk of having severe or moderate CMV disease was 3.28 times higher in patients with positive IgM. However the serological changes in CF were not significantly associated with the severity of the viral disease since 34.6 % of the patients with CF changes had a severe form versus 20.8% in the group without CF modification. Viruria was significantly associated with moderate or severe infection: 43.6% of the patients with viruria had severe infection versus only 12.5% in the patients without viruria (P < 0.0002). The risk of having moderate or severe CMV disease was 3.48 times higher in the patients with viruria. Viraemia was also associated with more severe CMV infection: 48.6% of moderate or severe CMV infection in the group of patients with viraemia versus 19% in the group without viraemia (P < 0.0001). The risk of having severe or moderate CMV infection was 2.58 times higher in the patients with viraemia. Viraemia was not more associated with severe CMV infection than viruria. Using the maximum likelihood ratio method and the logistic regression model, CMV-specific IgM, viruria and viraemia were each shown to be associated with the severity of CMV disease and the addition of one parameter to the other(s), whatever the type (except the CF changes) and whatever the order of this addition, did not remove the link between the severity and IgM, viruria and viremia. The incidence of severe and moderate CMV disease increased with the number of positive viral parameters (PVP) from 2% of moderate and severe infections in the group with one PVP, to 28% in the group with two PVP, to 39% in the group with three PVP and 68% in the group with four PVP (trend, 35.95; P < 0.0001). Taking the absolute risk of the group of patients without IgM, viruria or viraemia as the basal level, the observed relative risk of severe CMV infection varied from 6.45 in the group with positive IgM without viruria or viraemia, to 10.74 in the group with positive IgM and viruria without viraemia and to 22.5 in the group with the three positive parameters IgM, viruria and viraemia. The different potential confounding factors (recipient and donor serology, renal or renal and pancreatic transplantation, DR compatibility, rejection before CMV infection) did not modify the link between the viral profile and the severity of CMV disease. This study suggests that the severity of CMV disease might be linked to the overspread of the virus as well as to the consequences of a CMV-specific humoral immune response.     

Lipopolysaccharide-binding protein as a new and reliable infection marker after kidney transplantation

The early and reliable differentiation of rejections, viral infections and bacterial infections is one of the main problems after organ transplantation. One promising solution to this problem is the lipopolysaccharide-binding protein (LBP), which is regulated upwards in gram-negative sepsis and related conditions. Therefore, the aim of our study was to explore the diagnostic potential of LBP serum levels in well-defined, non-infectious and infectious events after kidney transplantation (KTx). In a retrospective study the LBP serum levels were measured in a total of 686 serum samples from 52 kidney graft recipients. In all pre-KTx sera tested, the mean LBP level was 8.8+/-3.5 microg/ml (reference range: 2.0-15.2 microg/ml). In 7 of 52 recipients without intraoperative T-cell depletion, the mean LBP level was significantly ( P<0.01) increased (13.0+/-1.5 microg/ml) at post-KTx day 1, but was within the reference range. In contrast, the intraoperative T-cell depletion by antilymphocyte antibodies resulted in a significant ( P<0.01) increase to 25.8+/-11.4 microg/ml (range: 13.3-47.2 microg/ml). In recipients with immediate ( n=14) or delayed ( n=9) graft function without any other complications, all post-KTx values (except the post-KTx peak) were within the reference range. In 10 recipients with steroid-sensitive rejections and in 11 recipients with steroid-resistant rejections, no rejection-associated changes of the LBP levels could be shown. In six recipients with cytomegalovirus infection, the detection of an antigenemia (pp65) also was not associated with alterations of the LBP levels. In addition, there was no correlation between LBP levels and the number of pp65-positive leukocytes in peripheral blood. In contrast, a strong elevation of LBP levels was seen in five recipients with gram-positive bacteremia as well as in other severe bacterial infections (e.g., purulent extravasate, heavily infected grafts, bacterial pneumonia and contaminated hematoma). In two recipients with superinfected (bacterial and mycotic or viral) Pneumocystis carinii pneumonias requiring assisted ventilation, LBP levels were elevated, too. Thus, in our study only systemic non-viral infections and massive lymphocytolysis were associated with elevated LBP serum levels.     

巨细胞病毒感染对肾移植受者的影响及其危险因素分析

目的 探讨巨细胞病毒（CMV）感染对肾移植受者的影响以及引起巨细胞病毒感染的危险因素。 方法 回顾性分析2000年1月至2004年12月892例肾移植的资料。按术后是否有巨细胞病毒感染分为病例组和对照组。应用Log-Rank检验比较两组1、3、5年人和肾存活率的差异；比较两组术后各种并发症发病率以及应用免疫抑制剂和抗病毒药物的差异。应用Logistic回归分析探讨巨细胞病毒感染的独立影响因素。 结果 病例组1、3、5年人存活率分别为81.3％、72.8％和54.8％，而对照组分别为96.4％、91.4％和79.9％，前者显著低于后者（Log-Rank值＝49.62，P < 0.01）。病例组1、3、5年移植肾存活率分别为71.0％、66.2％和46.1%，而对照组分别为91.5％、86.6％和74.5％，两者差异也有统计学意义（Log-Rank值44.87，P < 0.01）。病例组急性排斥发生率为24.9%，对照组为13.9%，前者显著高于后者（χ2＝14.49，P < 0.01）。Logistic回归分析表明，急性排斥、霉酚酸酯用量>2 g、应用抗胸腺细胞球蛋白（ATG）、抗淋巴细胞球蛋白（ALG）或OKT3是巨细胞感染的独立危险因素（OR值分别为1.464、3.097和2.837，P < 0.05)；应用更昔洛韦是巨细胞病毒感染的保护因素(OR值为0.234，P < 0.01)。 结论 巨细胞病毒感染显著降低了肾移植长期人和肾存活率。急性排斥、霉酚酸酯用量过大和应用抗淋巴细胞抗体是引起巨细胞病毒感染的独立危险因素。术后预防性应用更昔洛韦，可以有效减少巨细胞病毒感染。     

糖皮质激素在治疗肾移植术后巨细胞病毒性重症肺炎中的作用

目的探讨糖皮质激素在治疗肾移植术后巨细胞病毒(CMV)性重症肺炎中的作用。方法2002年1月至2004年10月发生肾移植后CMV性重症肺炎26例。选取2002年1月至2003年3月之间发病的12例为A组,2003年4月至2004年10月之间发病的14例为B组。发生CMV性重症肺炎后,A组治疗方案为:停用环孢素A(或他克莫司)和霉酚酸酯等免疫抑制剂,应用更昔洛韦等抗病毒药物,防治其它合并的感染,全身支持疗法,吸氧或呼吸机辅助通气等措施。B组除上述同样治疗措施外,还常规静脉应用甲泼尼龙(MP),起始剂量为120～150mg/d,3～5d后减量至80mg/d维持,当临床表现好转后再减量至40mg/d,应用时间为8～21d,平均12d。以后改为口服泼尼松维持。比较2组的治疗效果。结果A组应用呼吸机治疗9例(75%),其中死亡7例(58.33%),2例移植肾功能丧失,需透析治疗(16.67%);B组应用呼吸机治疗的4例(28.57%),其中死亡2例(14.29%),患者均无移植肾功能丧失。两组患者需用呼吸机治疗的几率和死亡率比较,B组均低于A组,差异均有统计学意义(P值分别为0.047和0.038)。B组患者中,均未出现激素相关的严重不良反应。结论应用适当剂量的甲泼尼龙,能有效减轻肾移植后CMV性重症肺炎的肺部炎症反应,并能减少因停用其它免疫抑制剂导致的移植肾排斥反应,降低死亡率和避免移植肾功能的丧失。     

肾移植后的尿路感染

目的了解近年肾移植后尿路感染的情况。方法分析我院420例肾移植后尿路感染的有关资料。结果7．4％发生尿路感染，其中67．8％发生在移植后1个月内。有发热者仅19．4％，有尿路刺激征者为12．9％，白细胞尿61．3％，合并败血症9．7％。病原菌以肠道菌属为主，但绿脓杆菌、混合感染、真菌感染的比例升高，共达29％。增加免疫抑制剂用量或使用抗淋巴细胞球蛋白/抗腺细胞球蛋白（ALG／ATG）或OKT3的患者更易发生尿路感染。结论肾移植后尿路感染值得临床医生重视。     

Cytomegalovirus infections following renal transplantation – effects of antiviral prophylaxis: a report of the North American Pediatric Renal Transplant Cooperative Study

Post-transplant cytomegalovirus (CMV) infections are a source of significant morbidity. However, the extent of the problem and the benefits of various antiviral prophylactic therapies remain incompletely understood. The North American Pediatric Renal Transplant Cooperative Study registry was screened to identify patients hospitalized for CMV infections during the 1st post-renal transplant year between 1987 and 1993. Using a control group of transplant recipients, we performed a retrospective analysis of risk factors for CMV disease among these hospitalized patients and studied the effects of various viral prophylactic strategies on CMV risk, clinical manifestations, and outcome. We identified 142 patients hospitalized with CMV infections, the majority of which included major organ involvement. A CMV-positive kidney donor was the most significant risk factor for hospitalization [odds ratio (OR) = 5.2, P<0.0001] irrespective of recipient age or CMV immune status. As opposed to antiviral agents (acyclovir, ganciclovir) or pooled IgG, prophylaxis with enriched anti-CMV IgG significantly reduced the risk of CMV hospitalization (OR = 0.31, P = 0.03). The prophylactic use of antiviral agents was associated with a decreased risk of major organ involvement during the CMV infection (OR = 0.34, P<0.005). Among the patients with CMV, the 3-year graft survival was significantly better for those who received any form of prophylaxis compared with those who received none (88% vs. 52%, P<0.001). Our findings suggest a role for combined CMV-enriched IgG and antiviral agent prophylaxis for post-transplant CMV disease. Such an approach could diminish the incidence and severity of CMV infection and appears to have an independent favorable effect on graft outcome. Received November 14, 1996; received in revised form March 21, 1997; accepted April 11, 1997     

Acyclovir plus CMV immunoglobulin prophylaxis and early therapy with ganciclovir are effective and safe in CMV high-risk renal transplant pediatric recipients

Abstract Cytomegalovirus (CMV) infection is still a major cause of morbidity in high-risk renal transplant recipients. In the present report, we have reviewed our records of renal transplant pediatric recipients (RTPR; mean age 14.1 ± 4.9 years) since 1991, when we started a policy of CMV prophylaxis constituting high-dose oral acyclovir plus CMV hyperimmune immunoglobulins (Hlg) followed by early i.v. ganciclovir therapy in high-risk patients (i.e., CMV donor +/ recipient -). Four patients received a kidney from a living relative (LR), 2 patients had one previous transplant, and 1 had a combined liver -kidney transplant. Thirty-three patients who were negative for CMV antibodies (ab) before transplantation received a kidney from CMV ab positive donors. The immunosuppressive regimen included cyclosporin A and steroids, with the addition of azathioprine in the 4 patients who received an LR kidney. Serial assessments for CMV antigenemia (pp 65) were routinely performed for 6 months after transplantation to define CMV infection. Among the 33 CMV seronegative recipients (R -) who received the graft from a CMV seropositive donor (D +), 18 (54.5 %) experienced CMV infection, whereas among the 28 CMV R +, who received a graft from a CMV D +, 11 (39.3 %) experienced CMV infection. With regard to CMV - related symptoms, only 2 patients suffered from a CMV syndrome (fever and leukopenia in 1 patient, fever and arthralgia in the other). In no case did the spectrum of CMV disease occur; only minor symptoms were present in 7 of the remaining CMV-infected patients (fever in 6 and leukopenia in 1). Rejection episodes and renal function did not differ between CMV-infected and non-CMV-infected patients. Our experiences support the use of prophylactic acyclovir plus CMV HIg followed by early therapy with i.v. ganciclovir to combat the risk of increased morbidity in high risk RTPR.     

测定CD3 8+ CD8+ T淋巴细胞在监测肾移植后巨细胞病毒感染中的作用

目的观察CD38+CD8+T淋巴细胞水平在肾移植后巨细胞病毒感染患者体内的变化,探讨其监测肾移植后巨细胞病毒活动性感染的可能性.方法分别应用流式细胞术和免疫组织化学方法测定56例肾移植受者手术前后的CD38+CD8+T淋巴细胞水平和巨细胞病毒白细胞抗原,并将两者结果进行比较.结果肾移植术前所有患者巨细胞病毒白细胞抗原均为阴性,其(CD38+CD8+)/CD8+的平均比值为0.11±0.05;肾移植后检测到有14例患者巨细胞病毒白细胞抗原阳性,出现阳性的时间为术后(32.7±16.6)d,(CD38+CD8+)/CD8+的比值在术后(29.6±8.4)d出现了有显著意义的升高,平均数值为0.43±0.21.这些患者接受静脉滴注丙氧鸟苷治疗后巨细胞病毒白细胞抗原转阴,(CD38+CD8+)/CD8+平均比值下降为0.16±0.09.治疗前后CD38+CD8+T淋巴细胞水平比较差异有显著性意义(P＜0.05).结论CD38+CD8+T淋巴细胞水平的检测结合巨细胞病毒白细胞抗原检查有助临床监测肾移植后CMV活动性感染.