Objectives

Alemtuzumab (Ale) is a recombinant monoclonal antibody which binds to CD52 causing profound lymphodepletion, thus allowing its use in renal transplantation induction therapy. However, patients may be at increased risk for opportunistic infections, such as Cytomegalovirus (CMV). We analyzed CMV infection in renal allograft recipients administered low-dose valganciclovir (VGCV) prophylaxis with alemtuzumab induction and steroid minimization.

Materials and methods

In this retrospective analysis, 678 kidney transplant recipients were evaluated, with 606 included for analysis. Patients were excluded for receiving induction therapy other than Ale, or for lack of follow-up within 1 year. VGCV prophylaxis was stratified by recipient CMV risk status and low-dose (450 mg) VGCV was given 3 times a week to low and moderate risk patients and daily to high risk individuals. Subject records were examined for recipient demographics, donor and recipient CMV serostatus, CMV viremia, and invasive infection.

Results

Of the 606 recipients, 154 were defined as low risk for CMV infection (donor and recipient both negative, or D−/R−), 236 as moderate risk without mismatch (D+/R+), 122 as moderate risk with mismatch (D−/R+), and 94 as high risk (D+/R−). Twenty-nine (29) individuals (4.8%) tested positive by PCR for CMV viremia and 10 (1.7%) patients developed invasive CMV disease, including colitis (n = 4), esophagitis (n = 1), enteritis (n = 1), nephritis (n = 1), and pneumonia (n = 3). High risk recipients (D+/R−) accounted for the majority of invasive CMV disease (n = 5), followed by moderate risk (n = 4). CMV viremia was also more common in high risk and moderate risk (D+/R+) individuals. Overall rejection rate for our study population was 27%.

Conclusion

In this institution's experience, CMV incidence was reduced compared to historically reported data by using low-dose (450 mg) VGCV prophylaxis in combination with Ale induction and steroid minimization. However, overall rejection rate was significantly higher in our population, possibly influenced by the degree of steroid minimization.

中文翻译：

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低剂量缬更昔洛韦作为预防巨细胞病毒的阿仑单抗引起的肾移植后接受者的一项单中心研究。

目标

Alemtuzumab（Ale）是一种重组单克隆抗体，可与CD52结合，引起严重的淋巴衰竭，因此可用于肾脏移植诱导治疗。但是，患者可能会面临巨细胞病毒（CMV）等机会性感染的风险增加。我们分析了低剂量缬更昔洛韦（VGCV）预防与阿仑单抗的诱导和类固醇的最小化的肾脏同种异体移植受者中的巨细胞病毒感染。

材料和方法

在这项回顾性分析中，评估了678位肾移植受者，其中606位接受了分析。排除患者接受除Ale以外的其他诱导治疗或1年内未进行随访。对VGCV的预防根据接受者CMV的风险状况进行分层，低剂量（450 mg）的VGCV每周3次给予中低风险患者，每天给予高风险患者。检查受试者记录的接受者人口统计学，供者和接受者CMV血清状况，CMV病毒血症和侵袭性感染。

结果

在606位接受者中，有154位被定义为CMV感染的低风险（供体和接受者均为阴性，或D- / R-），236位被定义为具有不匹配的中度风险（D + / R +），122位被定义为具有不匹配的中度风险（D- / R +），高风险（D + / R-）为94。经PCR检测为CMV病毒血症的29例（29）（4.8％）阳性，而10例（1.7％）患者发生了浸润性CMV疾病，包括结肠炎（n  = 4），食道炎（n  = 1），肠炎（n  = 1 ），肾炎（n  = 1）和肺炎（n  = 3）。高风险接受者（D + / R-）占大多数侵袭性CMV疾病（n  = 5），其次是中度风险（n = 4）。高危和中危（D + / R +）个体中CMV病毒血症也更为常见。我们研究人群的总排斥率为27％。

结论

在该机构的经验中，与历史报道的数据相比，通过使用低剂量（450 mg）VGCV预防措施与Ale诱导和类固醇最小化相结合，降低了CMV发生率。但是，总体排斥率在我们的人群中要高得多，这可能受类固醇最小化程度的影响。