肾移植早期巨细胞病毒感染对移植肾远期预后的影响

Affects of early cytomegalovirus infection on long-term renal prognosis in patients with renal transplantation

目的 :探讨肾移植受者术后早期巨细胞病毒 (CMV)感染与远期肾功能的关系。 方法 :自 1999年8月～ 2 0 0 1年 6月 ,根据肾移植术后 6个月内CMV pp6 5抗原血症指数 (I)和持续时间 ,将 96例随访达 3年的肾移植受者分为CMV非感染组 (I =0 )、低感染组 (I =1～ 30 )、短期高感染组 (I >10 0 ,≤ 2周 )和长期高感染组 (I >10 0 ,≥ 8周 ) ,比较四组在肾移植 6个月时肾功能、移植肾活检组织中转化生长因子 β1(TGF β1)蛋白和mRNA表达 ;随访 3年期内肌酐清除率 (Ccr)减损量、肾功不全发生率 ,并对出现肾功不全者在血肌酐 (SCr)升高 1个月内进行移植肾穿剌活检 ,以明确病因。 结果 :在肾移植 6个月时 ,四组肾功能无明显差异 (P >0 0 5 ) ,但“长期高感染组”肾组织中TGF β1蛋白和mRNA表达量明显大于其他 3组 ;在肾移植 3年时 ,“长期高感染组”Ccr下降了(16 2± 7 2 )ml/min ,4 3 5 % (10 / 2 3)患者出现肾功能不全 ,二者均明显大于其他 3组 (P <0 0 1,P <0 0 5 )。肾功不全者 ,移植肾活检均证实为慢性移植肾肾病。 结论 :肾移植术后早期长时间严重的CMV感染是影响移植肾远期肾功能、导致慢性移植肾肾病的重要原因。

Objective:Recent improvements in immunosuppression have led to a dramatic increase in shor t-term renal allograft survival. However, the long-term result of renal trans plant has not improved correspondingly because that chronic allograft nephropath y (CAN) makes the allograft fibrosis. Recently it has been found that cytomegal ovirus(CMV) infection can accelerate histologic changes in CAN. The aim of th is study is to investigate whether CMV infection is associated with long-term renal allograft function. Methodology:From August 1, 1999 to June 30, 2001, according to CMV-pp65 antigenemia (the nu mber of CMV-pp65-positive leukocytes) in peripheral blood within 6 months post -transplant, ninety-six renal transplant patients who had been followed up for 3-years were divided into four groups. When pp65 antigen load was higher than 100(×1/5×104 WBC)with the duration>8 weeks within 6 months post-transpl antation it was called long-time and high-level active CMV infection. They we re non-CMV infection (n=19), low-CMV infection (n=34), short time high -level (n=20) and long time high-level active CMV infection (n=23) gro ups. Biopsies were carried out at the 7th month after transplantation. Transfo rming growth factor-betal (TGF-β 1) being a key fibrogenetic cytokine was de tected in biopsied tissues. All of the patients were followed up at least 3 yea rs. Three years later, the creatinine clearances (Ccr) and numbers of renal dys function cases were compared among four groups. Whether there were renal lesion s caused by understanded factors, such as acute rejection and ciclosporin A into xication, was investigated by biopsies. Results:After 6 months of renal transplantaition, there were no significant differences in renal function among the four groups, however, the expression of TGF-β 1 m RNA and TGF-β 1-protein in the long time high-level active CMV infection gr oup was significantly higher (P<0.01) than that of other three groups. At 3 years after renal allograft, the renal function decreased significantly [mea n of Ccr=(16.2±7.2)ml/min] in the long time high-level active CMV infecti on group compared with other three groups (P<0.05). On pathology, the kid neys with renal dysfunction showed unspecific lesions such as interstitial fibro sis and tubule atrophy, which was the character of CAN. Conclusion:The kind of CMV infection was found to be a risk factor for long-term renal dys function. Severe CMV infection with long duration was associated with lower lon g-term survival rate of kidney graft, and also was a very important way to resu lt in chronic allograft nephropathy.