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移植肾巨细胞病毒感染:肾移植受者中伐昔洛韦预防与抢先治疗的随机试验

Intragraft cytomegalovirus infection: a randomized trial of valacyclovir prophylaxis versus pre-emptive therapy in renal transplant recipients.

作者信息

Reischig Tomás, Nemcová Jana, Vanecek Tomás, Jindra Pavel, Hes Ondrej, Bouda Mirko, Treska Vladislav

机构信息

Department of Internal Medicine I, Charles University Medical School and Teaching Hospital, Pilsen, Czech Republic.

出版信息

Antivir Ther. 2010;15(1):23-30. doi: 10.3851/IMP1485.

DOI:10.3851/IMP1485
PMID:20167988
Abstract

BACKGROUND

In a randomized study, we observed a higher incidence of biopsy-proven acute rejection with pre-emptive valganciclovir therapy as compared with valacyclovir prophylaxis for prevention of cytomegalovirus (CMV) disease after renal transplantation (RTx). Persistence of the virus within the allograft could stimulate the alloimmune response. The aim of our study was to evaluate intragraft CMV infection in patients randomized to the trial.

METHODS

RTx recipients at risk of CMV were randomized to pre-emptive therapy with valganciclovir (n=36) for significant CMV viraemia (> or =2,000 copies/ml by quantitative PCR in whole blood samples) or 3-month prophylaxis with valacyclovir (n=34). Renal biopsies performed during 12 months post-RTx were analysed for the presence of CMV by real-time PCR and immunohistochemical staining.

RESULTS

A total of 35 patients (59 biopsies) in the pre-emptive group and 31 patients (57 biopsies) with valacyclovir prophylaxis had > or =1 biopsy specimen with sufficient material for intragraft CMV determination. Cumulative incidence of intragraft CMV infection was 14% and 7% (P=0.315) with pre-emptive therapy and prophylaxis, respectively. Patients at risk for primary CMV infection (CMV serological donor-positive and recipient-negative) were at higher risk for intragraft CMV infection (40% versus 5%; P=0.008). CMV viraemia at the time of biopsy was associated with the presence of CMV within the allograft (P<0.001).

CONCLUSIONS

During the first year after RTx, the incidence of intragraft CMV infection was relatively low with comparable rates in patients managed by pre-emptive valganciclovir therapy and valacyclovir prophylaxis.

摘要

背景

在一项随机研究中,我们观察到,与使用伐昔洛韦预防肾移植(RTx)后巨细胞病毒(CMV)疾病相比,抢先使用缬更昔洛韦治疗经活检证实的急性排斥反应发生率更高。病毒在移植物内持续存在可能会刺激同种免疫反应。我们研究的目的是评估随机分组进入该试验的患者的移植物内CMV感染情况。

方法

有CMV感染风险的RTx受者被随机分为两组,一组接受缬更昔洛韦抢先治疗(n = 36),用于治疗显著的CMV病毒血症(全血样本定量PCR检测≥2000拷贝/ml),另一组接受伐昔洛韦3个月预防治疗(n = 34)。对RTx后12个月内进行的肾活检组织,通过实时PCR和免疫组化染色分析CMV的存在情况。

结果

抢先治疗组共有35例患者(59次活检),接受伐昔洛韦预防治疗组有31例患者(57次活检),各有≥1份活检标本有足够材料用于移植物内CMV检测。抢先治疗组和预防治疗组移植物内CMV感染的累积发生率分别为14%和7%(P = 0.315)。原发性CMV感染风险患者(CMV血清学供体阳性而受体阴性)发生移植物内CMV感染的风险更高(40%对5%;P = 0.008)。活检时的CMV病毒血症与移植物内存在CMV相关(P < 0.001)。

结论

在RTx后的第一年,抢先使用缬更昔洛韦治疗和伐昔洛韦预防治疗的患者中,移植物内CMV感染发生率相对较低,且发生率相当。

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