Badid Chérif, Desmouliere Alexis, Babici Daniela, Hadj-Aissa Aoumeur, McGregor Brigitte, Lefrancois Nicole, Touraine Jean Louis, Laville Maurice
Département de Néphrologie, Hôpital Edouard Herriot et EA 645, Laboratoire de Physiologie de l'Environnement, Faculté de Médecine Grange Blanche, Lyon, France.
Nephrol Dial Transplant. 2002 Nov;17(11):1993-8. doi: 10.1093/ndt/17.11.1993.
Renal myofibroblast infiltration has been shown to be strongly associated with renal function decline in several chronic renal diseases. The purpose of the present study was to investigate whether early detection of myofibroblast infiltration using alpha-smooth-muscle actin (alpha-SMA) expression in time-zero biopsies predicts renal allograft dysfunction.
We studied renal tissue from 38 renal transplant patients from whom biopsies had been taken after vascular anastomosis during transplantation to ascertain whether myofibroblasts infiltration predicts renal graft survival. Immunohistochemistry was performed on time-zero biopsies to determine alpha-SMA expression, and this was compared to annual glomerular filtration rate (GFR) variation and other parameters including cold ischaemic time (CIT), donor and recipient age, number of acute rejections, and delayed graft function (DGF). GFR was measured by inulin clearance during of 3 years of follow-up after the transplantation. Progressors were defined as patients with an annual GFR decline >5 ml/min/year.
We found a significant correlation between interstitial alpha-SMA expression in time-zero biopsies and GFR evolution during the post-transplantation course (r=0.60, P<0.001). Although progressors had greater interstitial alpha-SMA expression than non progressors (7.9+/-0.7 vs 4.3+/-0.4%), they showed only a tendency towards higher glomerular alpha-SMA expression. In addition, progressors had more interstitial fibrosis in time-zero biopsies than non-progressors. There was no relationship between alpha-SMA expression and CIT, donor and recipient ages, number of acute rejections, and occurrence of DGF.
This study suggests that alpha-SMA evaluation in time-zero biopsies, especially the combination of alpha-SMA expression and interstitial fibrosis, can strongly predict chronic renal allograft dysfunctions.
在几种慢性肾脏疾病中，肾肌成纤维细胞浸润已被证明与肾功能下降密切相关。本研究的目的是调查在移植即刻活检中使用α-平滑肌肌动蛋白（α-SMA）表达早期检测肌成纤维细胞浸润是否能预测肾移植功能障碍。
我们研究了38例肾移植患者的肾组织，这些患者在移植过程中血管吻合后进行了活检，以确定肌成纤维细胞浸润是否能预测肾移植存活。对移植即刻活检组织进行免疫组织化学检测以确定α-SMA表达，并将其与年度肾小球滤过率（GFR）变化以及其他参数进行比较，这些参数包括冷缺血时间（CIT）、供体和受体年龄、急性排斥反应次数以及移植肾功能延迟恢复（DGF）。在移植后的3年随访期间通过菊粉清除率测量GFR。进展者定义为年度GFR下降>5 ml/min/年的患者。
我们发现移植即刻活检组织中间质α-SMA表达与移植后过程中的GFR演变之间存在显著相关性（r = 0.60，P < 0.001）。尽管进展者的间质α-SMA表达高于非进展者（7.9±0.7%对4.3±0.4%），但他们仅表现出肾小球α-SMA表达较高的趋势。此外，进展者在移植即刻活检中的间质纤维化比非进展者更多。α-SMA表达与CIT、供体和受体年龄、急性排斥反应次数以及DGF的发生之间没有关系。
本研究表明，移植即刻活检中的α-SMA评估，尤其是α-SMA表达与间质纤维化的联合评估，能够有力地预测慢性肾移植功能障碍。
