Ishimura T, Ishida T, Fujisawa M
Department of Urology, Kawasaki Medical School, Matsushima, Kurashika, Japan.
Aktuelle Urol. 2003 Jul;34(4):234-8. doi: 10.1055/s-2003-41603.
Long-term renal allograft survival is limited mainly by the progressive process termed chronic allograft nephropathy (CAN) or chronic rejection. A pathological feature of CAN is characterized by progressive interstitial fibrosis. Transforming growth factor (TGF)-beta(1) plays an important role in fibrogenesis. We investigated whether the degree of TGF-beta(1) expression in early biopsy specimens routinely obtained from stable allografts at 100 days could predict fibrosis and graft dysfunction in the late phase by immunohistochemistry. Patients were children with a graft from related donors. We immunohistochemically determined intracellular and extracellular expression of TGF-beta(1) in the graft at 100 days using LC antibody (LC) for intracellular TGF-beta(1) and CC antibody (CC) for extracellular TGF-beta(1). We used the change in creatinine clearance between 100 days and 3 years after transplantation (Delta Ccr) as an index of long-term graft function. Image analysis was used to calculate the relative area involved by interstitial fibrosis in trichrome-stained sections of graft biopsy specimens at 100 days and 3 years, designating the change as Delta FI. Delta Ccr was - 4.2 +/- 9.4 mL/min in subjects with minimal early immunoreactivity for CC and - 20.5 +/- 5.9 mL/min in subjects with strong reactivity (p < 0.05). Delta Ccr was - 14.5 +/- 18.6 mL/min in subjects with minimal early immunoreactivity for LC and - 11.7 +/- 12.8 mL/min in those with strong reactivity. Delta FI in subjects with minimal CC reactivity (1.28 +/- 4.11 %) tended to be lower than in subjects with strong reactivity (8.45 +/- 15.47 %). Neither fibrosis at 100 days nor Delta FI differed between subjects with minimal and strong LC reactivity. Thus, extracellular TGF-beta(1) expression in grafts at 100 days after transplantation has an influence on long-term graft function and tends to be associated with increased graft fibrosis at 3 years.
长期肾移植存活主要受称为慢性移植肾病（CAN）或慢性排斥反应的进行性过程限制。CAN的一个病理特征是进行性间质纤维化。转化生长因子（TGF）-β1在纤维生成中起重要作用。我们通过免疫组织化学研究了在100天时从稳定移植肾常规获取的早期活检标本中TGF-β1的表达程度是否可以预测后期的纤维化和移植肾功能障碍。患者为接受相关供体移植肾的儿童。我们使用针对细胞内TGF-β1的LC抗体（LC）和针对细胞外TGF-β1的CC抗体（CC），通过免疫组织化学方法测定移植肾在100天时细胞内和细胞外TGF-β1的表达。我们将移植后100天至3年之间肌酐清除率的变化（ΔCcr）用作长期移植肾功能的指标。图像分析用于计算移植肾活检标本在100天和3年时三色染色切片中间质纤维化累及的相对面积，将其变化称为ΔFI。CC早期免疫反应性最低的受试者的ΔCcr为-4.2±9.4 mL/min，而反应性强的受试者为-20.5±5.9 mL/min（p<0.05）。LC早期免疫反应性最低的受试者的ΔCcr为-14.5±18.6 mL/min，而反应性强的受试者为-11.7±12.8 mL/min。CC反应性最低的受试者的ΔFI（1.28±4.11%）往往低于反应性强的受试者（8.45±15.47%）。LC反应性最低和最强的受试者之间，100天时的纤维化和ΔFI均无差异。因此，移植后100天时移植肾中细胞外TGF-β1的表达对长期移植肾功能有影响，并且在3年时往往与移植肾纤维化增加有关。
