采用分阶段策略预防肾移植后巨细胞病毒感染：对血清学高危患者进行预防治疗，对中危患者采取抢先治疗策略：这是两种选择的最佳结合吗？

A split strategy to prevent cytomegalovirus after kidney transplantation using prophylaxis in serological high-risk patients and a pre-emptive strategy in intermediate-risk patients: Combining the best of two options?

机构信息

Department of Nephrology, Antwerp University Hospital, Edegem, Belgium.

Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Antwerpen, Belgium.

出版信息

Transpl Infect Dis. 2021 Apr;23(2):e13467. doi: 10.1111/tid.13467. Epub 2020 Oct 22.

DOI:10.1111/tid.13467

PMID:32935909

Abstract

BACKGROUND

Cytomegalovirus (CMV) remains an important challenge after kidney transplantation. Current Transplantation Society International Consensus Guidelines recommend antiviral prophylaxis or pre-emptive therapy for high-risk CMV-seronegative recipients with a CMV-seropositive donor (D+/R-) and moderate-risk CMV-seropositive recipients (R+). However, a split strategy according to CMV serostatus is not specifically mentioned.

METHODS

We evaluated a split strategy to prevent CMV infection after kidney transplantation in which D+/R- patients received valganciclovir (VGC) prophylaxis for 200 days, and R + patients were treated pre-emptively according to CMV DNAemia. Patients were followed until 1-year post-transplant.

RESULTS

Between April 2014 and March 2018, 40 D+/R- and 92 R + patients underwent kidney transplantation. Forty-six percent received antithymocyte globulin (ATG) induction, and 98% was treated with calcineurin inhibitors, mycophenolic acid (MPA), and steroids. No D+/R- patient developed CMV disease during prophylaxis (median 200 days), but 15% developed post-prophylaxis or late-onset disease. Fifty-three percent developed neutropenia during prophylaxis, including 16/40 (40%) grade 3 or 4 neutropenia requiring reduction/discontinuation of MPA (30%) and/or VGC (35%), and an occasional need for granulocyte colony-stimulating factor (5%). In the R + group, 40% received antiviral therapy for a median duration of 21 days; 5% developed early-onset CMV disease. Only 5% developed neutropenia. D+/R + status (hazard ratio (HR) 2.09,P = .004) and ATG use (HR 2.81, P < .0001) were risk factors for CMV reactivation.

CONCLUSIONS

Prophylaxis leads to acceptable CMV control in high-risk patients but comes with a high risk of neutropenia. Pre-emptive therapy is effective and limits drug exposure in those at lower risk of CMV.

摘要

背景

巨细胞病毒（CMV）仍然是肾移植后的一个重要挑战。目前，移植学会国际共识指南建议对 CMV 阴性受者（D+/R-）和中度风险 CMV 阳性受者（R+）接受 CMV 阳性供体（D+/R+）进行抗病毒预防或先发治疗。然而，并没有特别提到根据 CMV 血清状态进行的分割策略。

方法

我们评估了一种肾移植后预防 CMV 感染的分割策略，其中 D+/R-患者接受缬更昔洛韦（VGC）预防治疗 200 天，而 R+患者则根据 CMV DNA 血症进行先发治疗。患者随访至移植后 1 年。

结果

2014 年 4 月至 2018 年 3 月，40 例 D+/R-和 92 例 R+患者接受了肾移植。46%的患者接受了抗胸腺细胞球蛋白（ATG）诱导，98%的患者接受了钙调磷酸酶抑制剂、霉酚酸（MPA）和类固醇治疗。在预防期间，没有 D+/R-患者发生 CMV 疾病（中位数 200 天），但 15%的患者发生了预防后或迟发性疾病。53%的患者在预防期间发生中性粒细胞减少症，包括 16/40（40%）例 3 或 4 级中性粒细胞减少症，需要减少/停用 MPA（30%）和/或 VGC（35%），偶尔需要使用粒细胞集落刺激因子（5%）。在 R+组中，40%的患者接受了抗病毒治疗，中位时间为 21 天；5%的患者发生了早发性 CMV 疾病。只有 5%的患者发生中性粒细胞减少症。D+/R+状态（风险比（HR）2.09，P=0.004）和 ATG 使用（HR 2.81，P<0.0001）是 CMV 再激活的危险因素。