Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Swiss Med Wkly. 2011 Oct 12;141:w13268. doi: 10.4414/smw.2011.13268. eCollection 2011.
It has been proposed that reactive oxygen species play a role in renal fibrosis. 8-OHdG, a metabolite of oxidative damage to leukocyte DNA, has been identified as a marker of oxidative stress in patients with chronic renal failure.
Seventy-four patients following nephrectomy were retrospectively enrolled. Immunohistochemical analysis of the renal expression of 8-OHdG in the nephrectomised kidneys was performed and associations between renal expression of 8-OHdG and renal fibrosis were evaluated.
Patients with higher interstitial fibrosis scores (IFS) and glomerular fibrosis scores (GFS) had significantly higher serum creatinine, lower estimated glomerular filtration rate (eGFR), increased percentage of chronic kidney disease (CKD) and urothelial cell carcinoma. The renal tissues with higher IFS had lower expressions of 8-OHdG in normal tubular cytoplasm (NTc) (35.7% vs. 64.3%, p = 0.011) and normal tubular nuclei (NTn) (28.6% vs. 71.4%, p = 0.023). Univariate analysis showed that IFS and GFS correlated with the NTc 8-OHdG expression and IFS negatively correlated with NTn 8-OHdG expression. Multivariate stepwise regression revealed that serum creatinine (r = 0.351 for IFS, p = 0.021; r = 0.563 for GFS, p < 0.001) and intensity of 8-OHdG expression in NTc (r = 0.397 for IFS, p = 0.01; r = 0.278 for GFS, p = 0.043) were the independent factors predicting IFS or GFS.
This study demonstrated that the intensity of 8-OHdG expression in NTc was associated with the severity of renal fibrosis.
活性氧在肾纤维化中起作用。8-OHdG 是白细胞 DNA 氧化损伤的代谢产物,已被鉴定为慢性肾衰竭患者氧化应激的标志物。
回顾性纳入 74 例肾切除术后患者。对肾切除术后肾脏中 8-OHdG 的肾表达进行免疫组织化学分析,并评估 8-OHdG 肾表达与肾纤维化之间的关系。
间质纤维化评分(IFS)和肾小球纤维化评分(GFS)较高的患者血清肌酐明显升高,估算肾小球滤过率(eGFR)降低,慢性肾脏病(CKD)和尿路上皮细胞癌的比例增加。IFS 较高的肾组织中正常管状细胞质(NTc)的 8-OHdG 表达较低(35.7%对 64.3%,p = 0.011),正常管状核(NTn)的 8-OHdG 表达较低(28.6%对 71.4%,p = 0.023)。单因素分析显示,IFS 和 GFS 与 NTc 8-OHdG 表达相关,IFS 与 NTn 8-OHdG 表达呈负相关。多因素逐步回归显示,血清肌酐(IFS 的 r = 0.351,p = 0.021;GFS 的 r = 0.563,p < 0.001)和 NTc 中 8-OHdG 表达强度(IFS 的 r = 0.397,p = 0.01;GFS 的 r = 0.278,p = 0.043)是预测 IFS 或 GFS 的独立因素。
本研究表明,NTc 中 8-OHdG 表达强度与肾纤维化的严重程度相关。