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接受抗胸腺细胞球蛋白诱导治疗的血清学阳性肾移植受者的巨细胞病毒预防:晚期巨细胞病毒疾病的结局和危险因素。

Cytomegalovirus prophylaxis in seropositive renal transplant recipients receiving thymoglobulin induction therapy: Outcome and risk factors for late CMV disease.

作者信息

Reusing Jose O, Feitosa Emanoela B, Agena Fabiana, Pierrotti Lígia C, Azevedo Luiz S F, Kotton Camille N, David-Neto Elias

机构信息

Renal Transplantation Service, Hospital das Clínicas, University of Sao Paulo Medical School, São Paulo, Brazil.

Transplant and Immunocompromised Host Infectious Diseases, Harvard Medical School, Infectious Diseases Division, Massachusetts General Hospital, Boston, MA, USA.

出版信息

Transpl Infect Dis. 2018 Oct;20(5):e12929. doi: 10.1111/tid.12929. Epub 2018 Jul 2.

Abstract

BACKGROUND

Anti-thymocyte globulin (ATG) therapy is a risk factor for cytomegalovirus (CMV) disease in renal transplant (RTx) recipients and therefore antiviral prophylaxis is commonly used. We evaluated the outcome of our current policy of 90 days of CMV prophylaxis in seropositive recipients given ATG and the risk factors for the occurrence of CMV disease after prophylaxis.

METHODS

We studied a retrospective cohort of 423 RTx (2010-2014) CMV-seropositive adults given ATG induction therapy.

RESULTS

54 (13%) patients developed CMV disease at a median of 163 days after transplant, of which 29 (54%) had viral syndrome and 25 (46%) had invasive disease. Median prophylaxis time (94 days) and immunosuppressive drugs were similar between groups (CMV vs no-CMV). Those with CMV disease had more deceased donors and higher donor age, lower lymphocyte count, and lower median eGFR at day 90. Multivariable logistic regression analysis at day 90 and 180 found that eGFR ≤40 ml/min/1.73 m (but not acute rejection) was associated with late CMV disease. In a separate validation cohort of 124 patients with 8% late CMV disease, eGFR ≤45 and lymphocyte count ≤800 cells/mm at the end of prophylaxis remained predictive of late CMV disease occurrence.

CONCLUSIONS

These data indicate that antiviral prophylaxis adequately prevented CMV in seropositive recipients given ATG, but late disease still occurred. Low eGFR and low lymphocyte count at the end of prophylaxis may help identify patients at higher risk of CMV disease.

摘要

背景

抗胸腺细胞球蛋白(ATG)治疗是肾移植(RTx)受者发生巨细胞病毒(CMV)疾病的一个危险因素,因此通常采用抗病毒预防措施。我们评估了目前对接受ATG治疗的血清学阳性受者进行90天CMV预防策略的效果,以及预防后发生CMV疾病的危险因素。

方法

我们对423例接受ATG诱导治疗的RTx(2010 - 2014年)CMV血清学阳性成年患者进行了回顾性队列研究。

结果

54例(13%)患者在移植后中位163天发生CMV疾病,其中29例(54%)有病毒综合征,25例(46%)有侵袭性疾病。两组(CMV感染组与未感染组)的中位预防时间(94天)和免疫抑制药物相似。发生CMV疾病的患者有更多的已故供体和更高的供体年龄,淋巴细胞计数更低,且在第90天时中位估算肾小球滤过率(eGFR)更低。在第90天和第180天进行的多变量逻辑回归分析发现,eGFR≤40 ml/min/1.73 m²(而非急性排斥反应)与晚期CMV疾病相关。在一个包含124例患者(8%发生晚期CMV疾病)的独立验证队列中,预防结束时eGFR≤45以及淋巴细胞计数≤800个细胞/mm³仍然可预测晚期CMV疾病的发生。

结论

这些数据表明,抗病毒预防措施能充分预防接受ATG治疗的血清学阳性受者发生CMV感染,但仍会发生晚期疾病。预防结束时低eGFR和低淋巴细胞计数可能有助于识别发生CMV疾病风险较高的患者。

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