优化巨细胞病毒抢先治疗与抗病毒预防用于预防巨细胞病毒高风险（D+R-）肾移植受者巨细胞病毒病的系统评价与荟萃分析

A Systematic Review and Meta-analysis of Optimized CMV Preemptive Therapy and Antiviral Prophylaxis for CMV Disease Prevention in CMV High-Risk (D+R-) Kidney Transplant Recipients.

作者信息

Kumar Lakshin, Murray-Krezan Cristina, Singh Nina, Brennan Daniel C, Rakita Robert M, Dasgupta Sayan, Fisher Cynthia E, Limaye Ajit P

机构信息

Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington, Seattle, WA.

Division of General Internal Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA.

出版信息

Transplant Direct. 2023 Jul 12;9(8):e1514. doi: 10.1097/TXD.0000000000001514. eCollection 2023 Aug.

UNLABELLED

The optimal strategy for cytomegalovirus (CMV) disease prevention in CMV donor/recipient kidney transplant recipients remains uncertain. Conclusions of prior meta-analyses that CMV disease rates with preemptive therapy (PET) and universal prophylaxis (UP) were comparable may have been affected by inclusion of studies lacking key determinants of efficacy of the respective strategies.

METHODS

We conducted a systematic review and meta-analysis of PET with weekly CMV polymerase chain reaction monitoring for ≥3 mo and UP with 6 mo of valganciclovir. PubMed and Embase databases were reviewed from January 1, 2010, to April 1, 2022. Risk of bias was assessed with 3 instruments (Cochrane RoB, Cochrane RoBINS-I, and an instrument for assessing risk in observational studies). The primary outcome was CMV disease incidence by 1-y posttransplant. Secondary outcomes by 1-y were graft loss, acute allograft rejection, and mortality. Results were synthesized using generalized linear mixed model meta-analysis. PET studies were stratified into low-threshold (LT) and high-threshold (HT) PET based on the viral load threshold for initiation of antiviral therapy.

RESULTS

Twenty-five studies met inclusion criteria (6 PET, 19 UP). CMV disease incidence was significantly higher in HT (0.30 [95% confidence interval (CI), 0.22-0.39]) versus LT PET (0.06 [95% CI, 0.03-0.12]). LT PET was associated with a significantly lower CMV disease incidence (0.06 [95% CI, 0.03-0.12]) versus UP (0.21 [95% CI, 0.17-0.27]). Incidence of graft loss, acute allograft rejection, or mortality was not significantly different between LT PET and UP ( > 0.05 for all comparisons). Receipt of lymphocyte-depleting antibodies was not associated with a significant difference in CMV disease incidence (odds ratio = 1.34 [95% CI, 0.80-2.25]).

CONCLUSIONS

LT PET is associated with a significantly lower incidence of CMV disease compared to UP with similar rates of other clinical outcomes. These findings provide rationale and preliminary data for a randomized superiority trial of optimized LT-PET versus UP in donor seropositive recipient seronegative kidney transplant recipients.

未标注

在巨细胞病毒（CMV）供体/受体肾移植受者中预防CMV疾病的最佳策略仍不确定。先前的荟萃分析得出结论，抢先治疗（PET）和普遍预防（UP）的CMV疾病发生率相当，但这可能受到纳入缺乏各自策略疗效关键决定因素的研究的影响。

方法

我们对采用每周CMV聚合酶链反应监测≥3个月的PET和采用6个月缬更昔洛韦的UP进行了系统评价和荟萃分析。检索了2010年1月1日至2022年4月1日的PubMed和Embase数据库。使用3种工具（Cochrane偏倚风险评估工具、Cochrane RoBINS - I以及一种观察性研究风险评估工具）评估偏倚风险。主要结局是移植后1年时的CMV疾病发生率。1年时的次要结局是移植物丢失、急性移植物排斥反应和死亡率。结果采用广义线性混合模型荟萃分析进行综合。根据启动抗病毒治疗的病毒载量阈值，PET研究被分为低阈值（LT）PET和高阈值（HT）PET。

结果

25项研究符合纳入标准（6项PET，19项UP）。HT组的CMV疾病发生率（0.30[95%置信区间（CI），0.22 - 0.39]）显著高于LT PET组（0.06[95%CI，0.03 - 0.12]）。与UP组（0.21[95%CI，0.17 - 0.27]）相比，LT PET组的CMV疾病发生率显著更低（0.06[95%CI，0.03 - 0.12]）。LT PET组和UP组之间移植物丢失、急性移植物排斥反应或死亡率的发生率无显著差异（所有比较P>0.05）。接受淋巴细胞清除抗体与CMV疾病发生率无显著差异（比值比 = 1.34[95%CI，0.80 - 2.25]）。