Xu L N, Zhao B, Wang H T, Cai J P, Mao Y H
Department of Nephrology, Beijing Hospital, National Center of Gerontology, Beijing 100730, China.
Zhonghua Yi Xue Za Zhi. 2018 Nov 13;98(42):3415-3419. doi: 10.3760/cma.j.issn.0376-2491.2018.42.008.
To investigate the relationship of DNA oxidative product 8-oxo-dGsn and RNA oxidative product 8-oxo-Gsn with chronic kidney disease (CKD). Between January 2015 and December 2016, 146 cases of CKD (30, 30, 31, 30 and 25 cases of CKD stage 1-5, respectively) were collected in the Department of Nephrology in Beijing Hospital. Among them, 70 cases were male, accounting for 47.95%. The age distribution ranged from 21 to 88 years, with an average age of (56.43±16.79) years. Their fasting blood and morning urine were collected. The levels of 8-oxo-dGsn and 8-oxo-Gsn in plasma and urine were quantified by isotope-diluted liquid chromatography mass spectrometry (MS)/MS (ID-LC-MS/MS). The urine 8-oxo-Gsn/Cr in patients with CKD stage 1-5 was (3.07±1.07) μmol/mol, (3.42±1.34) μmol/mol, (3.72±1.47) μmol/mol, (3.90±1.93) μmol/mol and (3.75±2.26) μmol/mol, respectively. The urinary 8-oxo-Gsn content in CKD stage 4 patients was significantly higher than those of other 4 stages (<0.05). The serum/urine ratio of 8-oxo-Gsn was 0.02±0.02, 0.03±0.02, 0.06±0.04, 0.10±0.05 and 0.34±0.03, respectively, and in CKD stage 4 and 5 patients, it increased significantly, especially in CKD stage 5 cases (<0.05). Expression of 8-oxo-Gsn had a good correlation with renal function[the Spearman 's correlation coefficient: serum 8-oxo-Gsn and serum creatinine was 0.629 (<0.001); urine/serum 8-oxo-Gsn and eGFR was 0.799 (<0.001); serum/urine 8-oxo-Gsn and serum/urine creatinine was 0.888 (<0.001)]. With age increasing, CKD patients showed increased RNA oxidation, and 8-oxo-Gsn increased significantly in patients over 60 years (<0.05). After multiple linear regression analysis, 8-oxo-Gsn was only associated with serum creatinine (β=0.656, =8.275, <0.001). Our finding indicates that the RNA oxidation occurs in patients with renal disease, and its oxidation increased as the disease progressing. The significant increase in the ratio of plasma and urinary 8-oxo-Gsn is of great importance on evaluating renal function.
探讨DNA氧化产物8-氧代脱氧鸟苷(8-oxo-dGsn)和RNA氧化产物8-氧代鸟苷(8-oxo-Gsn)与慢性肾脏病(CKD)的关系。2015年1月至2016年12月,北京医院肾内科收集了146例CKD患者(CKD 1-5期分别为30、30、31、30和25例)。其中男性70例,占47.95%。年龄分布为21至88岁,平均年龄为(56.43±16.79)岁。采集其空腹血和晨尿。采用同位素稀释液相色谱串联质谱法(ID-LC-MS/MS)对血浆和尿液中8-oxo-dGsn和8-oxo-Gsn的水平进行定量。CKD 1-5期患者尿8-oxo-Gsn/肌酐分别为(3.07±1.07)μmol/mol、(3.42±1.34)μmol/mol、(3.72±1.47)μmol/mol、(3.90±1.93)μmol/mol和(3.75±2.26)μmol/mol。CKD 4期患者尿8-oxo-Gsn含量显著高于其他4期(<0.05)。8-oxo-Gsn的血清/尿比值分别为0.02±0.02、0.03±0.02、0.06±0.04、0.10±0.05和0.34±0.03,在CKD 4期和5期患者中显著升高,尤其是CKD 5期患者(<0.05)。8-oxo-Gsn的表达与肾功能具有良好的相关性[Spearman相关系数:血清8-oxo-Gsn与血清肌酐为0.629(<0.001);尿/血清8-oxo-Gsn与估算肾小球滤过率(eGFR)为0.799(<0.001);血清/尿8-oxo-Gsn与血清/尿肌酐为0.888(<0.001)]。随着年龄增长,CKD患者RNA氧化增加,60岁以上患者8-oxo-Gsn显著升高(<0.05)。多线性回归分析后,8-oxo-Gsn仅与血清肌酐相关(β=0.656,t=8.275,P<0.001)。我们的研究结果表明,肾脏疾病患者存在RNA氧化,且随着疾病进展其氧化增加。血浆和尿液中8-oxo-Gsn比值的显著升高对评估肾功能具有重要意义。