肾移植术后巨细胞病毒感染的危险因素分析和血清甘露聚糖结合凝集素的预测价值

Risk factors of cytomegalovirus infection and the predictive value of mannose-binding lectin after renal transplantation

目的探讨肾移植受者巨细胞病毒(CMV)感染的危险因素,观察天然免疫分子甘露聚糖结合凝集素(mannose-binding lectin,MBL)对于肾移植术后CMV感染的预测价值。方法选择2010年1月到2011年6月在山东大学附属山东省千佛山医院接受肾移植的83例受者作为研究对象。入选受者均经伦理委员会批准及其本人的同意。所有受者随访时间≥6个月。随访期间定期采用实时荧光定量聚合酶链反应检测血液、尿液CMV脱氧核糖核酸(DNA)拷贝数,血液或浓缩尿中检测CMVDNA≥103copies/ml诊断为CMV感染。将83例受者分为CMV感染组和非CMV感染组,应用酶联免疫吸附试验(ELISA)检测两组肾移植受者术前血清MBL水平并进行比较。将可能影响CMV感染的6项指标先进行单因素分析,将有统计学意义的因素再进行多因素分析(Logistic回归),筛选出CMV感染的独立危险因素。结果随访6个月内共有18例(22%)受者发生CMV感染(CMV感染组),另65例受者未发生CMV感染(非感染组)。CMV感染组受者的术前血清MBL水平明显低于非感染组受者,两者比较差异有统计学意义(P<0.01)。18例CMV感染受者经更昔洛韦治疗后,病毒拷贝数下降转阴,无一例发生CMV肺炎或移植物失功。单因素分析发现术前供体CMV血清学阳性/受体阴性(D+/R-)、MBL<500ng/ml、应用抗胸腺细胞球蛋白和发生术后排斥反应是CMV感染的危险因素(分别为P=0.018、0.001、0.011、0.005)。Logistic回归分析发现术前MBL水平<500ng/ml是CMV感染的独立危险因素,优势比为5.691,95%可信区间1.746～18.548,P=0.004。CMV血清学阳性/受体阴性(D+/R-)亦是CMV感染的独立危险因素,优势比为7.673,95%可信区间1.107～53.178,P=0.039。结论术前MBL水平(<500ng/ml)和术前供体CMV血清学阳性/受体阴性是肾移植术后CMV感染的独立危险因素。术前检测受者的血浆MBL水平对术后CMV感染有预测价值,一旦术前检测血浆MBL<500ng/ml可以术前提前应用抗病毒预防治疗。在供受体配对方面,应尽量避免将血清CMV阳性供肾移植给CMV阴性的受体。

Objective To investigate the risk factors of cytomegalovirus （CMV） infection in renal transplant recipients and the predictive value of natural immune molecules mannose-binding lectin （MBL） on CMV infection after renal transplantation. Methods Eighty-three recipients who underwent renal transplantation in Affiliated Shandong Province Qianfoshan Hospital of Shandong University from January 2010 to June 2011 were selected as research subjects. This study was approved by local ethical committee and the informed consent of all participating subjects was obtained. All of the recipients were followed up at least 6 months. During the follow-up period, copies of CMV deoxyribonucleic acid （ DNA ） in blood and urine were detected by fluorescence quantitative polymerase chain reaction （FQ-PCR）. Patients were diagnosed as CMV infection when CMV DNA was over 103 copies/ml in blood or concentrated urine. Eighty-three recipients were divided into CMV infection group and non CMV infection group. The levels of pre-operative serum MBL of renal transplant recipients were detected by enzyme-linked immune absorbent assay （ELISA） and compared in two groups. One-way analysis was used in 6 factors which might affect CMV infection. Logistic multi-factor regression analysis was then used in significant factors of one-way analysis. And the independent risk factors were selected. Results During the follow-up period of 6 months, 18 recipients （22%） developed CMV infection （CMV infection group） , and 65 recipients didn＇t develop CMV infection （ non CMV infection group ）. The levels of serum MBL of recipients in CMV infection group before transplantation were significantly lower than those in non CMV infection group （ P 〈 0. 01 ）. After the therapy of ganciclovir, the copies of CMV decreased to negative in 18 recipients with CMV infection. No CMV pneumonia or graft dysfunction occurred. The result of one-way analysis showed that the risk factors of CMV infection included CMV serology positive of donors/negative of recipients （ D ＋/R - ） before transplantation, MBL 〈 500 ng：/ml, application of antithymocyte globulin and occurrence of rejection after transplantation （P = 0. 018, 0. 001, 0. 011, 0. 005, respectively）. The result of Logistic multi-factor regression analysis showed that the independent risk factor of CMV infection included the level of pre-operative MBL 〈 500 ng/ml before renal transplantation （odds ratio 5. 691, 95% confidence interval 1. 746-18. 548, P = 0. 004） and CMV serology positive of donors/negative of recipients （D ＋/R - ） （odds ratio 7. 673, 95% confidence interval 1. 107-53. 178, P = 0. 039）. Conclusions The level of pre- operative MBL （ 〈500 ng/ml） and CMV serology positive of donors/negative of recipients （D ＋/R-） before transplantation are the independent risk factors of CMV infection after renal transplantation. The level of serum MBL of recipients before transplantation can predict the occurrence of CMV infection after renal transplantation. If the level of serum MBL is detected lower than 500 ng/ml before renal transplantation, prophylaxis of virus infection should be applied before the operation. In pairing between donors and recipients, it should be avoided to transplant kidney from CMV serology positive donors to negative recipients.