de Matos A C Carvalho, Câmara N O Saraiva, Tonato E J, Durão Júnior M de Souza, Franco M F, Moura L A Ribeiro, Pacheco-Silva A
Division of Nephrology, Universidade Federal de São Paulo. Hospital do Rim e Hipertensão. Fundação Oswaldo Ramos, São Paulo, Brazil.
Transplant Proc. 2010 Nov;42(9):3482-8. doi: 10.1016/j.transproceed.2010.06.014.
The objective of this study was to show the morphologic characteristics of allograft renal biopsies in renal transplant patients with stable renal function, which can potentially be early markers of allograft dysfunction, after 5 years of follow-up.
Forty-nine renal transplant patients with stable renal function were submitted to renal biopsies and simultaneous measurement of serum creatinine (Cr). Histology was evaluated using Banff scores, determination of interstitial fibrosis by Sirius red staining and immunohistochemical study of proximal tubule and interstitial compartment (using cytokeratin, vimentin, and myofibroblasts as markers). Biopsies were evaluated according to the presence or absence of the epitheliomesenchymal transition (EMT). The interstitial presence of myofibroblasts and tubular presence of vimentin was also analyzed simultaneously. Renal function was measured over the follow-up period to estimate the reduction of graft function.
Median posttransplant time at enrollment was 105 days. Patients were followed for 64.3 ± 8.5 months. The mean Cr at biopsy time was 1.44 ± 0.33 mg/dL, and after the follow-up it was 1.29 ± 0.27 mg/dL. Nine patients (19%) had a reduction of their graft function. Eleven biopsies (22%) had tubulointerstitial alterations according to Banff score. Seventeen biopsies (34%) presented EMT. Fifteen biopsies (32%) had high interstitial expression of myofibroblasts and tubular vimentin. Using Cox multivariate analysis, HLA and high expression of interstitial myofibroblasts and tubular vimentin were associated with reduction of graft function, yielding a risk of 3.3 (P = .033) and 9.8 (P = .015), respectively.
Fibrogenesis mechanisms occur very early after transplantation and are risk factors for long-term renal function deterioration.
本研究的目的是展示肾功能稳定的肾移植患者同种异体肾活检的形态学特征，这些特征可能是随访5年后同种异体肾移植功能障碍的早期标志物。
49例肾功能稳定的肾移植患者接受了肾活检并同时测定血清肌酐（Cr）。使用班夫评分评估组织学，通过天狼星红染色测定间质纤维化，并对近端小管和间质区进行免疫组织化学研究（使用细胞角蛋白、波形蛋白和成肌纤维细胞作为标志物）。根据上皮-间质转化（EMT）的存在与否对活检进行评估。同时分析成肌纤维细胞的间质存在和波形蛋白的小管存在情况。在随访期间测量肾功能以评估移植功能的降低。
入组时移植后的中位时间为105天。患者随访了64.3±8.5个月。活检时的平均Cr为1.44±0.33mg/dL，随访后为1.29±0.27mg/dL。9例患者（19%）移植功能降低。根据班夫评分，11例活检（22%）有肾小管间质改变。17例活检（34%）出现EMT。15例活检（32%）间质成肌纤维细胞和小管波形蛋白高表达。使用Cox多变量分析，HLA以及间质成肌纤维细胞和小管波形蛋白的高表达与移植功能降低相关，风险分别为3.3（P = .033）和9.8（P = .015）。
纤维化机制在移植后很早就会出现，是长期肾功能恶化的危险因素。
