Shi Yujun, Tu Zhidan, Bao Ji, Sun Huaiqiang, Wang We, Luo Guangheng, Li Shengfu, Li Youping, Bu Hong
Key Laboratory of Transplant Engineering and Immunology, Ministry of Health, West China Hospital, Sichuan University, Chengdu, PR China.
Scand J Urol Nephrol. 2009;43(5):390-9. doi: 10.3109/00365520903142244.
To date, serum biochemistry examination and routine biopsy are the most commonly used methods to assess renal function after allogenic kidney transplantation. Connective tissue growth factor (CTGF) has been considered as a biomarker of chronic renal allograft injury characterized by tubular atrophy and interstitial fibrosis (TA/IF). This study explored the potential value of urinary CTGF as an early predictor of TA/IF using a rat model.
A Fisher to Lewis allogenic rat kidney transplant model was established and the recipients were killed at weeks 4, 8 and 12 post-transplantation. TA/IF was graded based on Banff Schema 1997. The location and expression of CTGF mRNA were detected by oligonucleotide-primed in situ DNA synthesis and quantitative polymerase chain reaction. CTGF protein expression was examined with immunohistochemistry and immunoblotting. Urinary CTGF concentration was measured by enzyme-linked immunosorbent assay. The correlation between urinary CTGF concentration and serum creatinine (SCr) and Banff score was analysed statistically.
Typical morphological changes including TA/IF in allograft appeared at week 8 and became very severe at week 12 post-transplantation. CTGF expression in epithelium was up-regulated early and urinary CTGF was markedly elevated from week 4. SCr in recipients was stable before week 8 but increased tremendously at week 12. Urinary CTGF concentration was positively correlated with SCr and degree of interstitial fibrosis.
Urinary CTGF increases earlier than the appearance of biochemical abnormalities and pathological changes. Measurement of urinary CTGF may offer a potential non-invasive strategy to predict the early onset of chronic renal allograft injury.
迄今为止，血清生化检查和常规活检是评估同种异体肾移植术后肾功能最常用的方法。结缔组织生长因子（CTGF）被认为是慢性肾移植损伤的生物标志物，其特征为肾小管萎缩和间质纤维化（TA/IF）。本研究使用大鼠模型探讨尿CTGF作为TA/IF早期预测指标的潜在价值。
建立Fisher到Lewis的同种异体大鼠肾移植模型，并在移植后第4、8和12周处死受体。根据1997年Banff标准对TA/IF进行分级。通过寡核苷酸引物原位DNA合成和定量聚合酶链反应检测CTGF mRNA的定位和表达。用免疫组织化学和免疫印迹法检测CTGF蛋白表达。采用酶联免疫吸附测定法测定尿CTGF浓度。对尿CTGF浓度与血清肌酐（SCr）及Banff评分之间的相关性进行统计学分析。
移植肾出现包括TA/IF在内的典型形态学改变出现在移植后第8周，并在第12周变得非常严重。上皮细胞中CTGF表达早期上调，尿CTGF从第4周开始显著升高。受体的SCr在第8周前稳定，但在第12周大幅升高。尿CTGF浓度与SCr及间质纤维化程度呈正相关。
尿CTGF升高早于生化异常和病理改变的出现。检测尿CTGF可能为预测慢性肾移植损伤的早期发生提供一种潜在的非侵入性策略。
