Fricke L, Steinhoff J, Hartwig-Weber I, Bein G
Klinik für Innere Medizin I, Medizinischen Universität zu Lübeck.
Dtsch Med Wochenschr. 1997 May 2;122(18):565-71. doi: 10.1055/s-2008-1047655.
Viral, especially cytomegalovirus (CMV), infections are after rejection reaction the most serious problem following organ transplantation. The risk of disease correlates with the CMV donor/recipient constellation and the degree of immunosuppression. The importance of antiviral prophylaxis remains unresolved. Whether drug prophylaxis adapted to the individual risk is of clinical value was investigated in a prospective study.
A risk-adapted stepwise antiviral prophylactic regimen was given to 62 patients with renal transplants. All patients at risk of CMV infection were given acyclovir, 200 mg four times daily for 3 months. Patients with rejection reaction for which they were receiving i.v. immunosuppressive treatment additionally received CMV hyperimmunoglobulin (2 ml/kg body weight on days 1 and 14). High-risk patients (donor CMV positive and recipient CMV negative) were given as basic prophylaxis CMV hyperimmunoglobulin i.v. on days 1 and 14 after transplantation, and additionally i.v. ganciclovir during any rejection treatment. The results were compared with those of a retrospectively selected patient cohort (n = 52) who had received only acyclovir as basic prophylaxis. The diagnosis of CMV infection was made by demonstrating CMVpp65 antigen in blood. In the prospectively studied patients measurement of beta 2 microglobulin concentration was used to determine viruria in 24-hour urine.
Among the high-risk group (donor CMV positive/recipient CMV negative) the additional prophylactic regimen significantly reduced the proportion of CMV-associated cases of rejection (14% compared with 42%, P < 0.05) in the basic prophylaxis only group. Similar results were obtained for CMV-caused transplant loss within the first 3 years (19% vs 50%, P < 0.05). The additional prophylaxis had no influence on the incidence of CMV infection. In case of active infection an isolated rise of beta 2-microglobulin in urine occurred in active infection at a mean of 6 days before CMVpp65 antigenaemia (sensitivity of 89%).
These results indicate that risk-adapted antiviral prophylaxis can decisively influence the long-term prognosis for a renal transplant, but not the incidence of CMV infection. The early and reliable diagnosis of active CMV infection is made possible by the combined use of beta 2-microglobulinuria and pp65 antigenaemia.
病毒感染，尤其是巨细胞病毒（CMV）感染，是器官移植后仅次于排斥反应的最严重问题。疾病风险与CMV供体/受体组合情况以及免疫抑制程度相关。抗病毒预防的重要性仍未解决。一项前瞻性研究调查了根据个体风险调整的药物预防是否具有临床价值。
对62例肾移植患者采用了根据风险调整的逐步抗病毒预防方案。所有有CMV感染风险的患者均接受阿昔洛韦治疗，每日4次，每次200mg，持续3个月。因排斥反应而接受静脉免疫抑制治疗的患者额外接受CMV高效价免疫球蛋白（第1天和第14天，2ml/kg体重）。高危患者（供体CMV阳性而受体CMV阴性）在移植后第1天和第14天接受静脉注射CMV高效价免疫球蛋白作为基本预防措施，并且在任何排斥反应治疗期间额外接受静脉注射更昔洛韦。将结果与一组回顾性选择的仅接受阿昔洛韦作为基本预防措施的患者队列（n = 52）的结果进行比较。通过检测血液中的CMV pp65抗原诊断CMV感染。在前瞻性研究的患者中，通过测量β2微球蛋白浓度来确定24小时尿液中的病毒尿情况。
在高危组（供体CMV阳性/受体CMV阴性）中，额外的预防方案显著降低了仅采用基本预防措施组中与CMV相关的排斥反应病例比例（分别为14%和42%，P < 0.05）。在最初3年内因CMV导致的移植失败情况也得到了类似结果（分别为19%和50%，P < 0.05）。额外的预防措施对CMV感染发生率没有影响。在活动性感染时，尿液中β2微球蛋白单独升高平均发生在CMV pp65抗原血症出现前6天（敏感性为89%）。
这些结果表明，根据风险调整的抗病毒预防可对肾移植的长期预后产生决定性影响，但对CMV感染发生率无影响。联合使用β2微球蛋白尿和pp65抗原血症可实现对活动性CMV感染的早期可靠诊断。
