Flechner S M, Avery R K, Fisher R, Mastroianni B A, Papajcik D A, O'Malley K J, Goormastic M, Goldfarb D A, Modlin C S, Novick A C
Section of Renal Transplantation, Department of Urology, The Cleveland Clinic Foundation, Ohio 44195, USA.
Transplantation. 1998 Dec 27;66(12):1682-8. doi: 10.1097/00007890-199812270-00019.
Posttransplantation cytomegalovirus (CMV) infection remains a significant cause of morbidity in kidney transplant recipients. We performed a randomized prospective controlled trial of oral acyclovir versus oral ganciclovir for CMV prophylaxis in a group of renal allograft recipients considered at high risk for CMV disease due to the use of OKT3 induction therapy.
A total of 101 recipients of cadaveric (83) and zero haplotype-matched live donor (18) kidney transplants were entered into the trial. A total of 22 D-R- patients received no prophylaxis. Twenty-seven D+R-, 29 D+R+, and 23 D-R+ patients were randomized to receive 3 months of either oral acyclovir (800 mg q.i.d.) or oral ganciclovir (1000 mg t.i.d.). Doses were adjusted according to the level of renal function. The D+R- patients were also given CMV immune globulin biweekly for 16 weeks. Surveillance blood cultures were obtained at transplantation, at months 1, 2, 3, and 6, and when clinically indicated. The primary study end points were time to CMV infection and disease the first 6 months after transplantation.
The mean follow up was 14.4 months. Both agents were well tolerated, and no drug interruptions for toxicity occurred. CMV was isolated in 14 of 39 (35.9%) acyclovir-treated and 1 of 40 (2.5%) ganciclovir-treated recipients by 6 months (P=0.0001). Symptomatic CMV disease occurred in 9 of 14 (64%) of the acyclovir patients, two with tissue-invasive disease. Infection rates for acyclovir vs. ganciclovir, respectively, stratified by CMV serology were: D+R-, 54 vs. 0%, P=0.0008; D+R+, 43 vs. 6.6%, P=0.01; D-R+, 8.3 vs. 0%, P=NS. No patient developed CMV infection while taking oral ganciclovir, however three delayed infections occurred 2-7 months after finishing therapy. Each patient had been previously treated for acute rejection.
Oral acyclovir provides effective CMV prophylaxis only for recipients of seronegative donor kidneys. Oral ganciclovir is a superior agent providing effective CMV prophylaxis for recipients of seropositive donor kidneys. Recipients who are treated for acute rejection are at risk for delayed CMV infection during the first posttransplantation year.
移植后巨细胞病毒（CMV）感染仍是肾移植受者发病的重要原因。我们进行了一项随机前瞻性对照试验，比较口服阿昔洛韦与口服更昔洛韦对一组因使用OKT3诱导治疗而被认为有CMV疾病高风险的肾移植受者进行CMV预防的效果。
共有101例尸体肾移植（83例）和零单倍型匹配活体供肾移植（18例）受者进入试验。共有22例D - R - 患者未接受预防治疗。27例D + R - 、29例D + R + 和23例D - R + 患者被随机分为接受3个月的口服阿昔洛韦（800毫克，每日4次）或口服更昔洛韦（1000毫克，每日3次）治疗。剂量根据肾功能水平进行调整。D + R - 患者还每两周接受16周的CMV免疫球蛋白治疗。在移植时、第1、2、3和6个月以及临床指征时采集监测血培养样本。主要研究终点是移植后前6个月发生CMV感染和疾病的时间。
平均随访时间为14.4个月。两种药物耐受性良好，未因毒性而中断用药。到6个月时，39例接受阿昔洛韦治疗的受者中有14例（35.9%）分离出CMV，40例接受更昔洛韦治疗的受者中有1例（2.5%）分离出CMV（P = 0.0001）。14例阿昔洛韦治疗的患者中有9例（64%）发生有症状的CMV疾病，其中2例有组织侵袭性疾病。按CMV血清学分层，阿昔洛韦与更昔洛韦的感染率分别为：D + R - ，54%对0%，P = 0.0008；D + R + ，43%对6.6%，P = 0.01；D - R + ，8.3%对0%，P = 无显著性差异。接受口服更昔洛韦治疗的患者未发生CMV感染，但有3例在完成治疗后2 - 7个月发生延迟感染。每位患者此前均接受过急性排斥反应治疗。
口服阿昔洛韦仅对血清阴性供肾受者提供有效的CMV预防。口服更昔洛韦是一种更优的药物，可为血清阳性供肾受者提供有效的CMV预防。接受急性排斥反应治疗的受者在移植后第一年有发生延迟CMV感染的风险。
