Nerpin Elisabet, Helmersson-Karlqvist Johanna, Risérus Ulf, Sundström Johan, Larsson Anders, Jobs Elisabeth, Basu Samar, Ingelsson Erik, Arnlöv Johan
Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, SE- 751 85, Uppsala, Sweden.
BMC Res Notes. 2012 Sep 27;5:537. doi: 10.1186/1756-0500-5-537.
The role of inflammation and oxidative stress in mild renal impairment in the elderly is not well studied. Accordingly, we aimed at investigating the associations between estimated glomerular filtration rate (eGFR), albumin/creatinine ratio (ACR), and markers of different inflammatory pathways and oxidative stress in a community based cohort of elderly men.
Cystatin C-based GFR, ACR, and biomarkers of cytokine-mediated inflammation (interleukin-6, high-sensitivity C-reactive protein[CRP], serum amyloid A[SAA]), cyclooxygenase-mediated inflammation (urinary prostaglandin F2α [PGF2α]), and oxidative stress (urinary F2 isoprostanes) were assessed in the Uppsala Longitudinal Study of Adult Men(n = 647, mean age 77 years).
In linear regression models adjusting for age, BMI, smoking, blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, and treatment with statins, ACE-inhibitors, ASA, and anti-inflammatory agents, eGFR was inversely associated with CRP, interleukin-6, and SAA (β-coefficient -0.13 to -0.19, p < 0.001 for all), and positively associated with urinary F2-isoprostanes (β-coefficient 0.09, p = 0.02). In line with this, ACR was positively associated with CRP, interleukin-6, and SAA (β- coefficient 0.09-0.12, p < 0.02 for all), and negatively associated with urinary F2-isoprostanes (β-coefficient -0.12, p = 0.002). The associations were similar but with lower regression coefficients in a sub-sample with normal eGFR (>60 ml/min/1.73 m2, n = 514), with the exception that F2-isoprostane and SAA were no longer associated with eGFR.
Our data indicate that cytokine-mediated inflammation is involved in the early stages of impaired kidney function in the elderly, but that cyclooxygenase-mediated inflammation does not play a role at this stage. The unexpected association between higher eGFR/lower albuminuria and increased F2-isoprostanes in urine merits further studies.
炎症和氧化应激在老年人轻度肾功能损害中的作用尚未得到充分研究。因此,我们旨在调查基于社区的老年男性队列中估计肾小球滤过率(eGFR)、白蛋白/肌酐比值(ACR)与不同炎症途径和氧化应激标志物之间的关联。
在乌普萨拉成年男性纵向研究(n = 647,平均年龄77岁)中,评估了基于胱抑素C的肾小球滤过率、ACR以及细胞因子介导的炎症(白细胞介素-6、高敏C反应蛋白[CRP]、血清淀粉样蛋白A[SAA])、环氧化酶介导的炎症(尿前列腺素F2α [PGF2α])和氧化应激(尿F2异前列腺素)的生物标志物。
在对年龄、体重指数、吸烟、血压、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯以及他汀类药物、血管紧张素转换酶抑制剂、阿司匹林和抗炎药治疗进行校正的线性回归模型中,eGFR与CRP、白细胞介素-6和SAA呈负相关(β系数为-0.13至-0.19,均p < 0.001),与尿F2异前列腺素呈正相关(β系数为0.09,p = 0.02)。与此一致,ACR与CRP、白细胞介素-6和SAA呈正相关(β系数为0.09至0.12,均p < 0.02),与尿F2异前列腺素呈负相关(β系数为-0.12,p = 0.002)。在eGFR正常(>60 ml/min/1.73 m2,n = 514)的子样本中,关联相似但回归系数较低,例外情况是F2异前列腺素和SAA与eGFR不再相关。
我们的数据表明,细胞因子介导的炎症参与了老年人肾功能损害的早期阶段,但环氧化酶介导的炎症在这个阶段不起作用。较高的eGFR/较低的蛋白尿与尿中F2异前列腺素增加之间意外的关联值得进一步研究。