Renal Transplantation - Calcutta Experience

31 renal transplant procedures have been performed at this centre. Renal donors were father in 4, mother in 4, brother in 12, sister in 4, brother-in-law in 1 and wives in 6 cases. Median age of recipients and donors was 35.2 years (20-55) and 38.3 years (24-60) respectively. After a mean follow up of 15.7 months (2-40), graft survival was 96.7% and patient survival 90-3%. Three patients (9.6%) required surgical re-exploration, one each for, peri-graft haematoma, arterial kink and graft artery thrombosis. 6 patients (19.3%) required anti rejection therapy with resultant complete normalisation of graft functions. Medical complications noted were post transplant diabetes mellitus in 6 (19.3%), azathihoprine induced bone marrow suppression in 1(3.2%), tuberculosis in 2 (6.4%), post transplant erythrocytosis in 2 (6.4%) and recurrent urinary tract infection (UTI) in one (3.2%) patients. 3 patients (9.6%) died with functioning graft, one due to lung infection and the other due to haemorrahagic pancreatitis and third due to infective endocarditis.Key Words: Post-transplant complications, Renal Transplantation     

更昔洛韦治疗婴儿巨细胞病毒肝炎合并中枢协调障碍的疗效观察

目的对更昔洛韦治疗婴儿巨细胞病毒肝炎合并中枢协调障碍的疗效和副作用进行评价。方法确诊的婴儿巨细胞病毒肝炎患儿,住院期间通过Vojta姿势发射结合肌张力检查筛选合并中枢协调障碍者。均给予更昔洛韦[总疗程6周5mg/(kg·次),每12h静滴1次,用2周后改每日1次]及综合治疗,疗程完成后评价脑损伤的恢复情况。结果80例婴儿巨细胞病毒肝炎患儿中极轻中枢协调障碍的有37.50%(30/80),轻度中枢协调障碍的18.75%(15/80),中度中枢协调障碍的7.50%(6/80),重度中枢协调障碍的3.75%0(3/80)。给予更昔洛韦及综合治疗后,脑损伤患儿部分恢复或症状有明显改善,前后比较差异有显著性。结论婴儿巨细胞病毒肝炎患儿合并有脑损伤的较多,应早期筛查以便及早作出干预措施。更昔洛韦治疗婴儿巨细胞病毒肝炎合并脑损伤患儿,可以促进脑损伤的恢复,副作用少。     

High dose intravitreal ganciclovir in the treatment of cytomegalovirus retinitis.

OBJECTIVE: To assess the role of intravitreal administration of high doses of ganciclovir as a supplement and alternative to intravenous administration in the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective study of visual outcome, relapse and complications of intravenous and high dose intravitreal administration of ganciclovir alone and in combination. METHOD: Twenty-three patients with AIDS and CMV retinitis (37 eyes) were examined by the authors and notes, fundal drawings and photographs reviewed. Initially patients were treated with intravenous ganciclovir alone and given supplementary intravitreal therapy for relapse or vision-threatening retinitis; however, later patients were managed with combination maintenance ganciclovir or maintenance intravitreal treatment alone. RESULTS: Relapse and loss of vision occurred frequently in patients treated with intravenous ganciclovir alone or in combination with intermittent intravitreal therapy. Eyes managed with maintenance high dose intravitreal ganciclovir alone or in combination with intravenous treatment did not relapse or lose vision. The most important complication of intravenous administration of ganciclovir was neutropenia (73% of patients), whereas that of intravitreal therapy was endophthalmitis (three eyes). CONCLUSION: High dose ganciclovir given intravitreally effectively suppressed CMV retinitis and preserved vision without adverse systemic effects or deterioration of quality of life.     

Cytomegalovirus infection as a complication of OKT3 therapy in kidney transplant recipients

We compared the incidence of clinical CMV illness in 25 renal transplant recipients treated with OKT3 for steroid resistant cellular rejection with 88 renal transplant patients treated only with conventional immunosuppression (cyclosporin A and steroids). Nine (36%) patients in the OKT3 group developed CMV illness compared to (2.3%) amongst those treated conventionally (p<0.0005). Patients who received OKT3 were divided into four groups according to the CMV antibody status of the donor and recipient. Six of the 9 episodes of CMV infection occurred in patients not previously exposed to CMV, who received a kidney from a CMV positive donor. Three (12%) of the patients treated with OKT3 died of CMV disease. A further 2 patients died of other causes giving an overall mortality in the OKT3 treated group of 20%. We concluded that when OKT3 therapy is used in association with donor/recipient CMV mismatch it is associated with a high CMV morbidity and mortality.     

术前巨细胞病毒感染对肾移植的影响

目的探讨术前巨细胞病毒(cytomegalovirus infection,CMV)感染对肾移植术后急性排斥反应(acute rejection,AR)的影响及术前预防性抗病毒治疗的意义.方法回顾性分析了116例肾移植受体的术前CMV感染和预防性抗病毒治疗情况,根据术前有无CMV感染分为感染组和非感染组,将CMV感染组肾移植受体根据有无预防性抗病毒治疗分为治疗组和非治疗组.同时检测35例正常健康者CMV结果.采用检测CMV-PP65抗原诊断CMV感染.结果术前CMV感染率肾移植受体为63.8%(74/116)高于正常健康者14.3%(5/35).术后发生CMV感染或CMV病非治疗组为5例(15.6%)高于治疗组1例(2.4%).发生急性排斥反应的术前CMV感染组为14例(18.9%)高于非感染组2例(4.8%).术后发生AR治疗组为4例(9.5%)低于非治疗组10例(31.3%).结论肾移植受体术前CMV感染发生率高于正常健康人群.预防性抗病毒治疗可以降低术后CMV感染或CMV病的发生率.术前CMV感染的肾移植受体术后AR发生率高于非感染者.对术前CMV感染患者采取预防性抗病毒治疗可以降低术后AR的发生率.     

肾移植术后带状疱疹的诊断与治疗

目的：探讨肾移植术后并发带状疱疹的诊治方法。方法：回顾性分析23例肾移植术后并发水痘-带状疱疹病毒（VZV）感染患者的临床资料。结果：肾移植患者并发VZV感染多发生在术后1～2年,根据患者临床表现及体征即可可诊断带状疱疹,23例患者在发生VZV感染后均根据血环孢素A（CsA）浓度谷值和峰值适当减少CsA用量,或调整免疫抑制剂联合用药方案。15例采用阿昔洛韦1200mg／d口服10～14天,治疗有效;另8例阿昔洛韦治疗效果不明显,改用更昔洛韦,剂量为500mg／d静脉滴注7～14天,治疗有效。所有患者在抗VZV感染的同时均使用抗生素,以防止合并细菌感染,并给予止痛、神经封闭等综合治疗。本组治疗总有效率为100％（23／23）。结论：肾移植术后VZV感染多发,诊断并不困难,治疗上合理用药非常重要,并相应调整免疫抑制治疗方案,阿昔洛韦和更昔洛韦对VZV感染有较好的疗效。     

Primary cytomegalovirus and opportunistic infections. Incidence in renal transplant recipients.

Thirty-five renal allograft recipients were studied concerning the relationship between cytomegalovirus (CMV), herpes simplex virus (HSV), and opportunistic bacterial and fungal infections. The incidence of opportunistic infections was determined for patients whose tests prior to transplantation were seronegative in complement fixation and indirect hemagglutination assays of CMV antibody and for those patients whose tests were seropositive. Among the six seronegative patients with seronegative tests, four (66%) experienced active CMV infection within two months, and four died of Candida or Aspergillus infection within six months after transplantation. Among the 22 patients with seropositive tests, only one (4%) had a fungal infection and it was nonfatal (P less than .05). The increased morbidity and mortality due to fungal and bacterial infections in transplant recipients with seronegative CMV tests appears, therefore, to be related to primary CMV infection rather than to generalized immunodeficiency.     

肾移植受者巨细胞病毒感染与抗心磷脂抗体的关系

目的：探讨肾移植受者巨细胞病毒（cytomegalovirus,CMV)感染与抗心磷脂抗体（anticardiolipin antibody,ACA)产生的关系。方法：肾移植受者146例术后采用定性聚合酶链反应（PCR）检测CMV－DNA，同时用酶 联免疫吸附法（ELISA）检测血清抗心磷脂抗体免疫球蛋白G（ACA-IgG），并与正常对照组（n=32)进行比较。结果：肾移植受者146例ACA阳性率为17．1％，与正常对照（6．3％）无明显差异；而CMV感染的肾移植受者ACA阳性率为31．2％，显著高于未感染CMV的受者（7．1％）及正常对照组（6．3％，P＜0．01）。结论：肾移植受者ACA的产生与CMV感染密切相关，可能是CMV导致移植肾慢性血管病变的原因之一。     

Human herpesvirus 6 infection in transplantation

Human herpesvirus 6 (HHV-6) is ubiquitous in the human population and causes exanthem subitum, a benign disease seen in infancy. The virus remains latent in the body after primary infection, and reactivates in immunocompromised patients. Infection occurs in nearly half of all bone marrow or solid organ transplant recipients 2-3 weeks following the procedure. It has been suggested that the viral infection and activation result in clinical symptoms including fever, skin rash, pneumonia, bone marrow suppression, encephalitis, and rejection. In order to control the viral infection, several studies investigating the route of viral transmission and diagnostic procedures have been carried out.     

异基因干细胞移植后间质性肺炎的预防和治疗

目的探讨异基因造血干细胞移植中巨细胞病毒（CMV）感染和间质性肺炎（IP）的预防和治疗。方法2002年9月至2005年9月对24例患者进行异基因造血干细胞移植，男14例，女10例，其中12例接受清髓性、12例接受非清髓性预处理方案移植。用膦甲酸钠联合阿昔洛韦预防CMV感染和IP，对已发生CMV感染或IP的患者，将阿昔洛韦改为更昔洛韦治疗。结果移植后有4例（16．7％）感染CMV，中位时间为移植后49d，经治疗后好转；有3例（12．5％）发生IP，其中2例CMV—DNA在正常范围，1例患者为巨细胞病毒间质性肺炎（CMV—IP）。经治疗后，3例IP1例死亡，2例好转。结论膦甲酸钠联合阿昔洛韦或更昔洛韦预防治疗IP效果良好。     

Clinical application of real time-polymerase chain reaction in determining cytomegalovirus viral DNA load in renal transplant recipients

Background Cytomegalovirus (CMV) remains a significant clinical problem among immunosuppressed renal transplant patients.Quantitative PCR assays have become the most common methods in the determination of CMV infections in transplant patients.This study was to determine the relationship between CMV infection and the acute rejection of the transplanted kidney.Methods Plasma samples from 77 renal transplant patients that were pre-transplant negative for CMV infection were tested using real-time quantitative PCR and CMV gene-specific primers.The detected viral loads were retrospectively compared with the acute rejection rate and the chronic or mild rejection rates of the renal transplant.Results CMV-DNA was detected in 29 of 77 recipients,yielding a positive rate of detection of 37.7％ for this procedure.Twelve of the 21 recipients (57.1％) who suffered acute rejection had positive CMV-DNA.Among the 56 recipients suffered from chronic or mild rejection,17 (30.4％) had positive CMV-DNA plasma.Moreover,of the 29 recipients who had detectable CMV-DNA after transplant,12 (41.4％) suffered from acute rejection; of the 48 recipients with undetectable CMV-DNA,only nine (18.8％) developed acute rejection.Post-transplant patients with acute rejection had a higher rate (57.1％ vs.30.4％,P=0.03) of post-transplant CMV infection than those with chronic or mild rejection.Conclusion CMV infection is a risk factor of acute renal transplant rejection and CMV infection should be prevented and treated in renal transplant recipients.Chin Med J 2012; 125(19):3575-3577     

肾骨髓联合移植与嵌合体发生及急性排斥反应的关系

目的　研究肾骨髓联合移植与嵌合体发生及急性排斥反应的关系。方法　采用供体骨髓与肾脏联合移植 ,进行 2 4例造血干细胞微嵌合体诱导 ,采用聚合酶链反应 (PCR)技术检测受者嵌合状态 ,与单纯肾脏移植组 37例比较嵌合发生率及急性排斥反应发生率。结果　随访 1年 ,肾骨髓联合移植组术后嵌合体发生率 (87 5 % ,2 1/ 2 4 )明显高于单纯肾脏移植组 (40 5 % ,15 / 37) ,差异有显著意义 (P 0 0 0 1) ;嵌合阳性组急性排斥反应发性率 (19 4 % ,7/ 36 )与嵌合阴性组 (44 % ,11/ 2 5 )相比差异有显著意义 (P <0 0 5 )。结论　肾骨髓联合移植可诱导嵌合体发生并增加受者对供体器官的免疫耐受 ,降低急性排斥反应发生率 ,嵌合现象与免疫耐受具有相关性     

Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis

We studied the effects of cytomegalovirus (CMV) infection on 301 cardiac transplant recipients who were treated during the cyclosporine era of immunosuppression (1980 to the present). These patients received varying combinations of cyclosporine, azathioprine, prednisone, rabbit antithymocyte globulin, and OKT3 as their immunosuppressive therapy. Two hundred ten patients were free of CMV infection (non-CMV group). During the same period CMV infection developed in 91 patients, as manifested by a fourfold IgG serologic titer rise, demonstration of CMV inclusion bodies in tissue, or positive cultures for the virus (CMV group). The rate of graft rejection was significantly higher in the CMV group. Graft atherosclerosis was significantly more severe in the CMV group as judged by angiographic criteria or by pathologic study. Patient survival rates were significantly lower in the CMV group. Death caused by graft atherosclerosis was significantly more common among patients in the CMV group. Finally, the graft loss rate (from either death or retransplantation for atherosclerosis) was significantly greater in the CMV group. These data demonstrate that CMV infection in cardiac transplant recipients is associated with more frequent rejection, graft atherosclerosis, and death.     

Rituximab induction therapy in highly sensitized kidney transplant recipients

Background  The number of highly sensitized patients is rising, and sensitization can lead to renal transplant failure. The present study aimed to investigate the safety and efficacy of renal transplantation following induction therapy with rituximab in highly sensitized kidney transplant recipients.

Methods  Seven highly sensitized kidney transplant recipients who underwent rituximab therapy from December 2008 to December 2009 were retrospectively analyzed. There were 3 men and 4 women, with a mean age of 38.5 years (range, 21–47 years). The duration of hemodialysis was 3–12 months, with a mean duration of 11 months. For 4 patients, this was the second transplant; the previous graft survival time was 2–11 years, with a mean survival time of 5.8 years. All the female recipients had history of multiple pregnancies, and all patients had previously received blood transfusions. All donors were men, with a mean age of 32.5 years (range, 25–37 years). In 2 of the 7 patients, both class I and class II of panel reactive antibody were high; the remaining 5 patients showed either high in class I or in class II of panel reactive antibody. The mean panel reactive antibody value was 31% for class I and 51% for class II respectively. The donors and the recipients had the same blood type, with low lymphocyte cytotoxicity ranging from 2% to 5%. The human leukocyte antigen (HLA) mismatch numbers were from 2 to 4. All patients received tacrolimus (0.1 mg∙kg^-1∙d^-1) and mycophenolate mofetil (750 mg twice per day) orally 3 days prior to surgery. All patients received a single dose of 600 mg rituximab (375 mg/m²) infusion on the day before surgery and polyclonal antibody (antithymocyte globulin) on the day of surgery. Postoperative creatinine, creatinine clearance rate, and occurrence of rejection by pathological biopsy confirmation were monitored.

Results  No patient had delayed graft function after surgery. Two patients had acute rejection, one on day 7 and the other on day 13 post-surgery. Diagnosis of acute rejections was based on the clinical assessments and pathological biopsy results. According to the Banff 07 classification of renal allograft pathology, one of the patients was Ia and the other was IIa; the C4d staining was negative in both patients. One patient received methylprednisolone plus cyclophosphamide and the other received antithymocyte globulin (ATG) therapy, both leading to successful reversion of the acute rejection. All patients were discharged postoperatively and all had normal renal function during the 7th to 12th month follow-up. Pulmonary infection occurred in 1 patient 4 months after surgery and was successfully cured.

Conclusion  Rituximab induction therapy can reduce the occurrence of postoperative humoral rejection in highly sensitized renal transplant recipients, suggesting that kidney transplantation may be safe and effective for these patients.

     

Coexistence of Th1/Th2 and Th17/Treg imbalances in patients with allergic asthma

Background  Recent recognition is that Th2 response is insufficient to fully explain the aetiology of asthma. Other CD4⁺ T cells subsets might play a role in asthma. We investigated the relative abundance and activities of Th1, Th2, Th17 and CD4⁺CD25⁺ Treg cells in patients with allergic asthma.

Methods  Twenty-two patients with mild asthma, 17 patients with moderate to severe asthma and 20 healthy donors were enrolled. All patients were allergic to house dust mites. Plasma total IgE, pulmonary function and Asthma Control Questionnaire were assessed. The proportions of peripheral blood Th1, Th2, Th17 and CD4⁺CD25⁺ Treg cells were determined by flow cytometry. The expression of cytokines in plasma and in the culture supernatant of peripheral blood mononuclear cells was determined by enzyme linked, immunosorbent assay.

Results  The frequency of blood Th2 cells and IL-4 levels in plasma and culture supernatant of peripheral blood mononuclear cells were increased in all patients with allergic asthma. The frequency of Th17 cells and the plasma and culture supernatant levels of IL-17 were increased, whereas the frequency of CD4⁺CD25⁺ Treg cells and plasma IL-10 levels were decreased in patients with moderate to severe asthma. Dermatophagoides pteronyssinus specific IgE levels were positively correlated with the percentage of blood Th2 cells and plasma IL-4 levels. Forced expiratory volume in the first second was negatively correlated with the frequency of Th17 cells and plasma IL-17 levels, and positively correlated with the frequency of Treg cells. However, mean Asthma Control Questionnaire scores were positively correlated with the frequency of Th17 cells and plasma IL-17 levels, and negatively correlated with the frequency of Treg cells.

Conclusions  Imbalances in Th1/Th2 and Th17/Treg were found in patients with allergic asthma. Furthermore, elevated Th17 cell responses, the absence of Tregs and an imbalance in Th17/Treg levels were associated with moderate to severe asthma. 

     

造血干细胞移植后巨细胞病毒感染临床分析

目的观察各种类型的造血干细胞移植（HSCT）后巨细胞病毒（CMV）感染的发生情况及疗效。方法选择我院59例异基因造血干细胞移植（allo—HSCT）和自体造血干细胞移植（auto—HSCT）患者移植后不同时期血和尿标本，检测CMV—pp65抗原及（或）CMV—DNA（荧光定量PCR法）进行动态观察分析。CMV感染的预防采用更昔洛书（DHPC）5～10mg／kg，1次／12h，分别在移植前第8天至移植当天及当CMV血清学检测阳性或发生CMV病时应用2-4周，并可同时应用大剂量丙种球蛋白。结果CMV感染在allo—HSCT后好发，非亲缘性移植CMV感染率高，9例allo—HSCT出现CMV感染发生在移植后＋42-＋68天，其中5例均存在不同程度的移植物抗宿主病（GVHD），尤其是Ⅱ～Ⅳ度急性GVHD，2例进展为巨细胞间质性肺炎（CMV-1P）；多为既往CMV感染被激活，对CMV—DNA阳性而无症状者进行预防治疗可使CMV—DNA阴转，可降低CMV病的发生。结论CMV病是allo—HSCT的常见并发症及主要致死原因之一；因此积极防治GVHD的发生及发展、定期监测CMV血清学阳性患者、早期干预性治疗可以提高移植的成功率。     

The use of oral ganciclovir in the treatment of cytomegalovirus retinitis in patients with AIDS.

OBJECTIVE: To recommend the appropriate use of oral ganciclovir as an alternative to intravenous (i.v.) maintenance therapy for cytomegalovirus (CMV) retinitis in patients with AIDS. OPTIONS: i.v. infusion of ganciclovir and foscarnet have been the only approved choices for maintenance therapy until the introduction of oral ganciclovir. OUTCOMES: Ease of administering maintenance therapy and improved quality of life for patients with AIDS. VALUES: The medical advisory group comprised physicians treating patients with AIDS therapy. Ease of administration of maintenance therapy and quality of patients' lives were considered important. BENEFITS, HARMS AND COSTS: Oral ganciclovir is a safe and convenient alternative to i.v. maintenance therapy for patients with CMV retinitis. However, its low bio-availability precludes its use for induction therapy and necessitates careful monitoring for compliance. Compared with i.v. administration of ganciclovir, oral maintenance therapy is cost effective. EVIDENCE: Evidence for the guidelines was gathered from data presented at a symposium on CMV retinitis and oral ganciclovir, clinical trials of oral ganciclovir and input from a visiting expert. It was presented at a meeting of the advisory board whose members are involved in the care of patients with AIDS and the management of CMV retinitis. The guidelines were approved by each member of the advisory board. RECOMMENDATIONS: Diagnosis, treatment and follow-up of CMV retinitis should always be in consultation with an ophthalmologist who is experienced in treating this disease. The patient should be fully informed about the limitations of the oral form of ganciclovir; he or she should be involved in decision making and carefully monitored. Oral ganciclovir should not be used for induction therapy or for maintenance therapy in high-risk patients. VALIDATION: Similar guidelines have been produced in England where the drug has been available since January 1995. SPONSOR: The deliberations of the advisory board and the preparation of this report were funded through an educational grant from Hoffmann-La Roche (Canada).     

Bone marrow granulomas in mononucleosis

Two patients with mononucleosis, one due to cytomegalovirus (CMV), and the other due to Epstein-Barr virus (EBV), presenting with high fever, malaise and hepatitis, had granulomas in the bone marrow but not in the liver. In patients who have unexplained fever, bone marrow granulomas may be a clue to CMV or EBV infection and need not initially raise the fear of prognostically more severe illness.     

巨细胞病毒检测及在异基因造血干细胞移植中应用研究

目的:探讨检测巨细胞病毒(CMV)的方法学及在异基因造血干细胞移植(Allo-HSCT)中临床应用的价值.方法:以45例Allo-HSCT为研究对象,采集移植前供者、移植前后及恢复期受者的抗凝血标本,分别采用CMV-pp65单克隆抗体免疫组化法和ELISA法,检测CMV早期抗原和IgG、IgM抗体,并进行多点动态观察.结果:45例患者163份系列标本,CMV早期抗原阳性75份,是在移植后6～242天首次检出,平均70天;其中≤45天出现阳性者26例,占58%.术前供、受者CMV-IgG抗体均阳性,CMV-IgM抗体供、受者各1例阳性,其中受者持续阳性.术后45例中21例出现CMV-IgM抗体阳性,首次检出时间在14～234天,平均127天,比早期抗原检出时间推迟近2个月.45例中因CMV感染而致间质性肺炎25例,占55%.结论:异基因造血干细胞移植采用CMVpp55单克隆抗体免疫组化法检测巨细胞病毒感染,快捷、准确、灵敏,对患者的诊断、治疗和预后判断有重要意义,值得推广.     

Immunomodulatory therapy of cytomegalovirus pneumonia after liver transplantation

Background There has been increasing interest in the research into cytomegalovirus （CMV） pneumonia agter liver transplantation （LT）. This study was undertaken to investigate the immunomodulatory therapy of CMV pneumonia after LT. Methods Six patients with CMV pneumonia after LT from October 2003 to November 2005 were analyzed retrospectively. They were diagnosed according to clinical manifestations, chest X-ray findings and pathogenic changes and given comprehensive therapy including mainly immunomodulation therapy and anti-viral medication. At the early stage of CMV pneumonia, the dose of immunosuppressive agents was decreased or ceased, instead replaced by immunoenhancement therapy. During recovery period from CMV pneumonia, the dose of immunosuppressive agents was given again or enhanced, and immunoenhancement therapy was ceased. The liver function of the patients was monitored closely during the treatment. Results In this series, five patients were survived and one died. The liver function of the six patients remained normal during the treatment, and no episode of acute rejection took place. Conclusions Poor immunity is the pathogenic basis of CMV pneumonia after LT. At early stage of CMV pneumonia, the immunity of the patients should be enhanced, and during the recovery period from CMV pneumonia, immunosuppresants shoud be given again but immunoenhancement therapy ceased. Individualized immunomodulatory therapy is essential to the treatment of CMV pneumonia after LT.