Viklický O, Matl I, Voska L, Böhmová R, Jaresová M, Lácha J, Lodererová A, Stríz I, Teplan V, Vítko S
Department of Nephrology, Transplant Center, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
Physiol Res. 2003;52(3):353-60.
Chronic allograft nephropathy (CAN) represents a frequent and irreversible cause of long-term renal graft loss. TGF-beta1 is a key profibrogenic cytokine associated with CAN pathogenesis. Because of clinical diagnostic inaccuracy, protocol biopsy has been suggested to be a beneficial method for early CAN detection. Protocol core biopsy was carried out in 67 consecutive cyclosporine-based immunosuppression-treated kidney transplant recipients with stable renal function 12 months after renal transplantation. Biopsy specimens were analyzed morphologically according to Banff-97' criteria and immunohistologically for TGF-beta1 staining. The data obtained were correlated with plasma TGF-beta1 levels and clinical data. CAN (grade I-III) was found in 51 patients (76 %). CAN grade I was found to be the most frequent one (44 %). A normal finding within the graft was made in only 12 patients (18 %). Clinically silent acute rejection Banff IA was present in 4 patients (6 %). In 8 patients (12 %) with CAN, borderline changes were present. We found a significant correlation between CAN grade and creatinine clearance, as measured by the Cockroft-Gault formula (p<0.01) as well as body mass index (p<0.01). There was a significant correlation between chronic vasculopathy (Banff cv) and creatinine clearance, and between the degree of TGF-beta1 staining and chronic vasculopathy (p<0.01). There were no relations between morphological findings and TGF-beta1 plasma levels, cyclosporine levels, plasma lipids, HLA-mismatches, panel reactive antibodies (PRA), proteinuria, and the donor's age. In conclusion, CAN is a frequent finding in protocol kidney graft biopsies 12 months after transplantation. TGF-beta1 tissue expression is linked with chronic vasculopathy.
慢性移植肾肾病（CAN）是长期肾移植失败的常见且不可逆原因。转化生长因子-β1（TGF-β1）是与CAN发病机制相关的关键促纤维化细胞因子。由于临床诊断存在误差，建议采用定期活检作为早期检测CAN的有效方法。对67例接受基于环孢素免疫抑制治疗且肾功能稳定的肾移植受者在肾移植12个月后进行了定期核心活检。活检标本根据Banff-97标准进行形态学分析，并进行TGF-β1染色的免疫组织学分析。所获数据与血浆TGF-β1水平及临床数据相关联。51例患者（76%）发现有CAN（I-III级）。I级CAN最为常见（44%）。仅12例患者（18%）移植肾表现正常。4例患者（6%）存在临床无症状的急性排斥反应Banff IA。8例（12%）CAN患者存在临界变化。我们发现CAN分级与通过Cockroft-Gault公式测得的肌酐清除率（p<0.01）以及体重指数（p<0.01）之间存在显著相关性。慢性血管病变（Banff cv）与肌酐清除率之间、TGF-β1染色程度与慢性血管病变之间存在显著相关性（p<0.01）。形态学结果与TGF-β1血浆水平、环孢素水平、血脂、HLA错配、群体反应性抗体（PRA）、蛋白尿及供体年龄之间无相关性。总之，CAN是移植后12个月定期肾移植活检中的常见发现。TGF-β1组织表达与慢性血管病变相关。
