Abstract
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.
Highlights
Reactive oxygen species (ROS), composed of superoxide radicals, hydrogen peroxide and hydroxyl radicals, are involved in the aging process but are either directly or indirectly implicated in a wide variety of clinical disorders, such as atherosclerosis, reperfusion injury, pulmonary toxicity, macular degeneration, cataractogenesis, diabetes, cancers and renal fibrosis [1,2]
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
The renal tissues with higher IFS had lower expressions of 8-OHdG in normal tubular cytoplasm (NTc)
Summary
Reactive oxygen species (ROS), composed of superoxide radicals, hydrogen peroxide and hydroxyl radicals, are involved in the aging process but are either directly or indirectly implicated in a wide variety of clinical disorders, such as atherosclerosis, reperfusion injury, pulmonary toxicity, macular degeneration, cataractogenesis, diabetes, cancers and renal fibrosis [1,2]. It is difficult to directly measure these free radicals because of a very short half life, products of radical damage to DNA, lipids, proteins and protective species are good markers of oxidative stress [3]. Recent studies have focused on measuring 8-OHdG, which is a major DNA oxidation product, and its free base 8-hydroxyguanine (8-OH-G) in blood cells or urine as an important biomarker of oxidative DNA damage induced by ROS [4,5]. High glucose, advanced glycation end products, angiotensin II and TGFβ1 are considered to increase intracellular ROS in renal cells and contribute to the development and progression of diabetic renal injury [2, 8]. As we needed human renal tissues with various degrees of fibrosis, we performed this study using remnant tissues from nephrectomised kidneys instead of renal tissues from biopsies
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