肾移植受者早期巨细胞病毒感染对远期肾功能的影响

Long-term Renal Allograft Dysfunction Associated with Cytomegalovirus Infection

目的明确肾移植受者术后早期巨细胞病毒(CMV)感染与远期肾功能损害的关系。方法自1999年8月-2001年4月,根据肾移植术后6个月内CMV-pp65抗原血症指数和持续时间,对182例肾移植受者进行分组,并于术后第7个月对各组部分患者做移植肾穿刺活检,比较肾组织中关键的纤维发生因子即转化生长因子β1(TGF-β1)的表达;对各组患者进行至少3年的前瞻性观察,3年后比较各组肌酐清除率(Ccr);对肾功不全的患者通过活检排除急性排斥反应、环孢素A中毒等有着明确原因的肾损害。结果高CMV-pp65抗原血症指数(>100)、且持续时间长(>8周)的患者,在术后第7个月时,肾组织中TGF-β1蛋白和TGF-β1mRNA的表达量明显大于其他患者,该组在术后3年内Ccr减少了(16.1±7.7)mL/min、有45.5%(10/22)的患者肾功不全,两者均明显高于其他患者。肾功能不全者移植肾活检,病理显示出间质纤维化、肾小管萎缩等慢性移植物肾病(CAN)所具有的非特异性改变。结论肾移植术后早期长时间高活动性的CMV感染是削弱移植肾远期功能、导致肾功不全的又一重要原因。

Purpose This study is to investigate whether cytomegalovirus （CMV） infection is associated with long-term renal allograft dysfunction. Methods From August 1, 1999 to April 30, 2001, according to CMV-pp65 antigenemia （the number of CMV-pp65-positive leukocytes） in peripheral blood within 6 months posttransplant, 182 patients who had had kidney transplantation were divided into four groups. Biopsies were carried out at the 7th month after transplantation. Transforming growth factor-betal （TGF-β1） being a key fibrogenetic cytokine was detected in biopsied tissues. All of the patients were followed up at least three years. Three years later, creatinine clearances and numbers of renal dysfunction cases were compared between four groups. Whether there were renal lesions caused by understanded factors, such as acute rejection and ciclosporin A intoxication, was investigated by biopsies. Results Patients whose pp65 antigen load was higher than〉100/5×10^4 WBC with the duration〉8 weeks within 6 months post-transplantation （called long-time and high-level active CMV infection）, their expression of TGF-β1 mRNA and TGF-β1-protein in the allografts was more than others at the 7th month after transplantation. Three years later, this group of patients had had loss of renal function by （16.1±7.7） mL/min in creatinine clearances and had more number of renal dysfunction cases. The difference was significant. On pathology, the kidneys with dysfunction showed unspecific lesions such as interstitial fibrosis and tubule atrophy which is the character of chronic allograft nephropathy （CAN）. Conclusions Serious CMV infection with long duration is associated with lower long-term survival rate of kidney graft. This kind of CMV infection was found to be a risk factor for long-term renal dysfunction.