Department of Medicine, Stavanger University Hospital, Stavanger, Norway.
Department of Natural Sciences, University of Agder, Kristiansand, Norway.
Free Radic Biol Med. 2020 Aug 1;155:10-18. doi: 10.1016/j.freeradbiomed.2020.05.005. Epub 2020 May 16.
IgA nephropathy (IGAN) is characterized by oxidative stress and inflammation. In the present study, we explored the relationship of redox status vs. that of circulating inflammation-related factors with other biomarkers in patients with IGAN.
This is a case-control study comparing patients with IGAN (Stage 1-4) to healthy controls. Forty patients and 40 controls were matched for age and sex. Two circulating dynamic redox parameters were analysed: oxidized free cysteine (Cys) and nitrate. Thirty-seven inflammation-related factors were measured in serum.
The patients had elevated levels of oxidized free Cys and nitrate, indicating the presence of oxidative stress. Nine circulating inflammation-related factors were higher in the serum of patients than in that of controls. The most important factors were APRIL, MMP-3, osteopontin, TNFR1 and TWEAK. Inflammation-related factors were positively correlated with oxidized free Cys, nitrate, creatinine and parathyroid hormone (PTH) in the patients. The correlation coefficients of Latent Inflammatory Factor vs. oxidized free Cys and nitrate were r = 0.43 (p = 0.007) and r = 0.51 (p = 0.001), respectively. This finding persisted after adjusting for the glomerular filtration rate.
Patients with IGAN had disturbed redox status. Several circulating inflammation-related factors were elevated, suggesting activation of the non-canonical NF-kB pathway. There was a positive relationship between systemic redox status and the level of inflammation-related factors, partially independent of GFR. The present findings raise the question of whether circulating oxidized free Cys and/or nitrate may be employed as prognostic biomarkers for IGAN in the future.
IgA 肾病(IGAN)的特征是氧化应激和炎症。本研究旨在探讨氧化还原状态与循环炎症相关因子与 IGAN 患者其他生物标志物的关系。
这是一项病例对照研究,比较了 IGAN(1-4 期)患者与健康对照组。40 名患者和 40 名对照者按年龄和性别匹配。分析了两种循环动态氧化还原参数:氧化游离半胱氨酸(Cys)和硝酸盐。测量了 37 种血清炎症相关因子。
患者的氧化游离 Cys 和硝酸盐水平升高,表明存在氧化应激。患者血清中 9 种循环炎症相关因子高于对照组。最重要的因子是 APRIL、MMP-3、骨桥蛋白、TNFR1 和 TWEAK。炎症相关因子与患者的氧化游离 Cys、硝酸盐、肌酐和甲状旁腺激素(PTH)呈正相关。潜在炎症因子与氧化游离 Cys 和硝酸盐的相关系数分别为 r=0.43(p=0.007)和 r=0.51(p=0.001)。调整肾小球滤过率后,这一发现仍然存在。
IGAN 患者的氧化还原状态受到干扰。几种循环炎症相关因子升高,提示非经典 NF-kB 通路被激活。全身氧化还原状态与炎症相关因子水平之间存在正相关关系,部分独立于 GFR。目前的研究结果提出了一个问题,即循环氧化游离 Cys 和/或硝酸盐是否可能在未来作为 IGAN 的预后生物标志物。