亲属活体肾移植受者术后巨细胞病毒肺炎的单中心10年诊治经验总结

Cytomegalovirus pneumonia after living-related donor kidney transplantation ： the experiences of one single center within 10 years

目的总结单中心亲属活体肾移植受者术后巨细胞病毒（cytomegalovirus，CMV）肺炎的诊治经验。 方法回顾性分析2005年4月至2014年9月收治的168例亲属活体肾移植术受者的临床资料，其中34例术后出现CMV肺炎，男26例，女8例。年龄19～57岁，平均32岁。34例患者CMV肺炎发病距肾移植手术时间为12～402 d，平均（91.7±60.8）d。发病至就诊时间为1～14 d，平均（6.4±3.7） d。症状表现为发热34例，胸闷或呼吸困难18例，咳嗽11例，乏力或肌肉酸痛6例。起病后最高体温38.0～40.0℃，平均（38.8±0.5）℃。34例发热时血常规白细胞计数（3.0～21.0）×109/L，平均（10.5±4.4）×109/L，其中升高18例，正常14例，降低2例。Q-PCR法检测34例患者血液标本中CMV DNA为（0.5～53.0）×103拷贝/ml，平均（9.3～15.8）×103拷贝/ml。胸片和/或CT主要表现为双肺或单肺斑片状阴影或间质性肺炎改变。单纯CMV感染者22例，合并其他病原感染者12例，包括卡氏肺孢子虫8例，甲型溶血性链球菌、奈瑟球菌、白假丝酵母菌各3例，肺炎克雷伯菌2例，金黄色葡萄球菌、屎肠球菌、铜绿假单胞菌、人葡萄球菌、表皮葡萄球菌各1例。 结果抗病毒治疗采用静脉滴注更昔洛韦5 mg/kg，1次/12 h，共14～21 d；后改为5 mg/kg，1次/d。糖皮质激素治疗首先采用静脉滴注甲泼尼龙200 mg/d，3～5 d后减量为160mg/d，3～5 d后减量至120 mg/d，3 d后减量至80 mg/d，3 d后减量至40 mg/d，3～5 d后减量至肾移植术后常规剂量，即口服泼尼松10～25 mg/d。早期应用广谱抗生素（三代头孢类、三/四代喹诺酮类或碳青霉烯类）预防细菌感染。早期常规应用复方磺胺甲恶唑预防卡氏肺孢子虫肺炎。定期行血、尿、痰细菌及真菌培养，根据培养结果及时调整治疗方案并选择有效的抗细菌、病毒或真菌治疗。34例中30例临床治愈。疾病病程（发病时间至临床治愈时间）12～52 d，平均（28.5±9.4）d。救治无效者4例，均合并其他病原感染，发生急性呼吸窘迫综合征、呼吸衰竭而死亡。 结论CMV肺炎是亲属活体肾移植术后较常见的感染性并发症。CMV肺炎易并发其他微生物感染，并成为肾移植患者术后死亡原因之一。及早明确诊断，早期抗病毒治疗联合及时有效的抗细菌、真菌治疗可提高CMV肺炎的治愈率。

Objective To report one-center experience on diagnosis and treatment of cytomegalovirus （CMV） pneumonia in recipients after living-related donor kidney transplantation （LDKT）. Methods The clinical and follow-up data of 168 recipients after LDKT from April 2005 to September 2014 were analyzed retrospectively. We analyzed the general information, clinical manifestation, treatment and outcomes of 34 recipients who were diagnosed as CMV pneumonia. Of the 34 patients, 26 were male and 8 were female. The average age were 32. 0 years old. Thirty-four patients developed CMV pneumonia between 12 to 402 days with an average of （91.7 ±60. 8） days post-transplant. It was （6. 4 ±3.7） d（range 1-14 d） from the onset of illness to seeking medical intervention. All cases presented with fever, 18 cases with dyspnea, 11 cases with cough and 6 cases with myalgia or fatigue. The highest temperature was （38.8±0. 5）℃ （range 38. 0-40. 0℃ ）. Leukocyte count was （10. 5 ±0. 4） × 109/L, elevated in 18 cases, normal in 14 cases, reduced in 2 cases. Quantitative polymerase chain reaction（PCR） assay for CMV DNA was （9.3-15.8） × 103 copies/ml for active CMV infection. Chest X ray or CT of all cases demonstrated patchy shadow or interstitial pneumonia. The etiological examination showed that 12 cases were complicated with other microorganism, including 8 cases with Pneumocystis carinii, 3 cases with Streptococcus A,3 cases with Neisseria, 3 cases with candida albicans, 2 cases with klebsiella pneumoniae, Staphylococcus aureus, enterococcus faecium, Pseudomonas aeruginosa varied 1 case. Results In antiviral therapy, patients were treated by introvenous ganciclovir 5 mg/kg every 12 h for 14-21d and then 5 mg/kg every day. Glucocorticoid treatment included intravenous methylprednisolone 200 mg/kg for 3-5 d, then gradually reduced to 160 mg/kg for 3-5 d, 120 mg/kg for 3 d,80 mg/kg for 3 d,40 mg/kg for 3-5 d,until to the original oral dose. Early application of broad-spectrum antibiotics was to prevent bacterial infection, and routine application of compound sulfamethoxazole to prevent Pneumocystis carinii pneumonia. Treatment options were adjusted according to periodic bacteria and fungal culture in blood, urine or sputum, and effective anti bacterial, viral or fungal treatment was selected. After administration of antiviral therapy, methylprednisolone, treatment for other microorganism, as well as adjusted immunosuppressive drugs, 30 cases were cured. The total course of the pneumonia lasted for （28.5 ± 9.4） days on average. However, 4 patients complicated with other microorganism died of severe pneumonia and acute respiratory distress syndrome（ARDS）. Conclusion CMV infection was a common complication of living-related donor kidney transplantation. CMV infection often complicated with other microbial infections, and became one of the causes of death after renal transplantation. Early diagnosis, early antiviral therapy combined with effective anti bacterial, fungal treatment would improve the survival of kidney transplant recipients.