Orlić Petar, Dvornik Stefica, Husnjak Smiljana Cuka, Aralica Merica, Orlić Lidija, Zivcić-Cosić Stela, Sladoje-Martinović Branka, Fućak Marina
Klinika za kirurgiju, Klinicki bolnicki centar Rijeka, Tome Strizića 3, 51000 Rijeka, Hrvatska.
Acta Med Croatica. 2003;57(1):49-52.
Cytomegalovirus (CMV) infection is the most common infectious complication after organ transplantation. Serology is useful only for detecting previous CMV infection. Dissatisfied with serologic follow-up after kidney transplantation, three years ago we introduced detection of CMV antigenemia by an immunocytochemical method using a monoclonal antibody specific for the pp65 CMV matrix protein. This test allows for quantification of positive leukocytes. The purpose of this paper is to present our three-year experience.
From May 1999 till May 2002 CMV antigenemia was examined in 76 patients: 55 patients submitted to kidney transplantation during the study period, and 21 patients previously. Antigenemia became positive at 25.68 +/- 15.51 days after transplantation. These 76 patients were divided into three groups according to the number of positive cells per 200,000 leukocytes: < 5 (group I), 6-20 (group II) and > 20 (group III). The groups consisted of 23, 20 and 11 patients, respectively. The percentage of patients treated by ganciclovir was 4.34%, 15% and 100%, respectively. In group I only one patient received ganciclovir because of geographic indication, in group II three patients because of septicemia, thrombopenia and leukopenia and previous miliary tuberculosis.
One patient from group III with steroid diabetes died from pneumonia with abscess formation three days from admission. In another two patients, interstitial pneumonia and abscess of the arm developed. Five patients had an acute rejection episode each and were treated by high doses of methylprednisolone. Five patients had elevated temperature, transaminases were elevated in five patients, and neutropenia with or without thrombopenia was found in six patients. One patient had recurrent CMV disease and lymphocele. Two patients had preemptive treatment by ganciclovir based on positive CMV antigenemia.
Various centers differ according to the approach to treatment of CMV infection, ranging from prophylaxis to deferred treatment for CMV disease. Determination of pp65 CMV antigenemia allowed us a safe follow-up of patients after kidney transplantation. Compared with previous serologic follow-up antigenemia is a considerable progress. We did not use CMV prophylaxis because it is more expensive and can cause resistance to ganciclovir. A promising novel drug valganciclovir will allow for good prophylaxis owing to its better absorption from the gut. Based on our three-year experience, optimal cut-off for antigenemia has been set at 20 positive cells per 200,000 leukocytes. The existence of symptoms or changes in the level of leukocytes, platelets or transaminases goes in favor of treatment decision.
Cytomegalovirus pp65 antigenemia is a reliable tool in the follow-up of patients after kidney transplantation. Patients with primary CMV infection, those with rejection episode and threshold of 20 positive cells require preemptive treatment with ganciclovir. The measurement of pp65 CMV antigenemia has clinical, analytical and cost-effective advantages. Intensive monitoring for CMV infection allows for quick and specific detection of active CMV infection. This approach avoids resistance to ganciclovir. The method is simple and specific without expensive equipment. Avoidance of unnecessary prophylaxis adds to its cost-effectiveness.
巨细胞病毒(CMV)感染是器官移植后最常见的感染性并发症。血清学仅有助于检测既往CMV感染。由于对肾移植后的血清学随访不满意,三年前我们引入了一种免疫细胞化学方法检测CMV抗原血症,该方法使用针对CMV pp65基质蛋白的单克隆抗体。此检测可对阳性白细胞进行定量。本文旨在介绍我们三年来的经验。
1999年5月至2002年5月,对76例患者进行了CMV抗原血症检测:研究期间接受肾移植的患者55例,既往接受肾移植的患者21例。移植后25.68±15.51天抗原血症呈阳性。这76例患者根据每200,000白细胞中阳性细胞数分为三组:<5个(I组)、6 - 20个(II组)和>20个(III组)。每组分别有23例、20例和11例患者。接受更昔洛韦治疗的患者百分比分别为4.34%、15%和100%。I组中仅1例患者因地理因素接受了更昔洛韦治疗,II组中有3例患者因败血症、血小板减少症、白细胞减少症及既往粟粒性肺结核接受了更昔洛韦治疗。
III组中有1例患有类固醇糖尿病的患者入院三天后死于伴有脓肿形成的肺炎。另外2例患者分别出现间质性肺炎和手臂脓肿。5例患者各发生一次急性排斥反应,并接受了大剂量甲泼尼龙治疗。5例患者体温升高,5例患者转氨酶升高,6例患者出现中性粒细胞减少,伴或不伴有血小板减少。1例患者发生复发性CMV疾病和淋巴囊肿。2例患者基于CMV抗原血症阳性接受了更昔洛韦抢先治疗。
不同中心对CMV感染的治疗方法各异,从预防到对CMV疾病的延迟治疗。CMV pp65抗原血症的检测使我们能够对肾移植后的患者进行安全随访。与既往血清学随访相比,抗原血症是一个显著的进步。我们未使用CMV预防措施,因为其费用更高且可能导致对更昔洛韦产生耐药性。一种有前景的新型药物缬更昔洛韦因其在肠道的吸收更好,将有助于良好的预防。基于我们三年的经验,抗原血症的最佳临界值设定为每200,000白细胞中有20个阳性细胞。症状的出现或白细胞、血小板或转氨酶水平的变化有利于治疗决策。
CMV pp65抗原血症是肾移植后患者随访的可靠工具。原发性CMV感染患者、发生排斥反应的患者以及阳性细胞数阈值为20个的患者需要用更昔洛韦进行抢先治疗。CMV pp65抗原血症的检测具有临床、分析和成本效益优势。对CMV感染的强化监测可快速、特异性地检测出活动性CMV感染。这种方法可避免对更昔洛韦产生耐药性。该方法简单、特异,无需昂贵设备。避免不必要的预防措施增加了其成本效益。