Association between Biomarkers of Carbonyl Stress with Increased Systemic Inflammatory Response in Different Stages of Chronic Kidney Disease and after Renal Transplantation

Association between Biomarkers of Carbonyl Stress with Increased Systemic Inflammatory Response in Different Stages of Chronic Kidney Disease and after Renal Transplantation
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DOI:
10.1159/000318792
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发表时间:
2010-01-01
影响因子:
--
通讯作者:
Pecoits-Filho, Roberto
Pecoits-Filho, Roberto
中科院分区:
其他
文献类型:
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作者:
Aveles, Paulo R.;Criminacio, Ciro R.;Pecoits-Filho, Roberto

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背景:慢性肾脏病(CKD)的特点是进行性肾功能障碍伴尿毒症毒素的积聚,以及氧化还原状态和促氧化剂生成之间潜在的失衡,导致氧化应激和慢性炎症,这与并发症(特别是心血管疾病)有关。我们的目的是分析一组CKD患者血浆总硫醇浓度(抗氧化能力的指标)和蛋白质羰基含量(羰基应激的标志)与肾功能和炎症的关系。患者和方法:CKD患者68例(2~5期,平均年龄57±12岁,男性46%,糖尿病患者34%)和21例活体供肾移植患者(平均年龄36±17岁,男性50%,糖尿病患者10%,肾移植后9+/-2个月)。分别用DTNB法和DNPH法测定血浆总硫醇和蛋白质羰基水平,并将其调整为血浆白蛋白浓度。常规方法检测血浆纤维蛋白原和C反应蛋白(CRP)水平,并作为炎症标志物。结果:平均肾小球滤过率为48ml/m in,肾小球滤过率与硫醇呈正相关(r=0.25p<0.05),与羰基(r=-0.26,p<0.05)、纤维蛋白原(r=-0.45,p<0.0001)、C反应蛋白(r=-0.14,p=ns)呈负相关。羰基与C反应蛋白(0.49,p<0.0001)和纤维蛋白原(0.30,p<0.01)密切相关。肾移植后血浆羰基水平(1.4nmo1/mg白蛋白)较术前(2.0nmo1/mg白蛋白,p<0.001)显著降低,与硫醇水平(15+/-4vs.21+/-5nmo1/mg白蛋白,p<0.05)的改善同步。此外,移植后C反应蛋白与羰基有显著的相关性(r=0.65;p<0.005)。结论:我们观察到,随着肾功能的恶化,慢性肾脏病患者呈现氧化还原状态的改变,羰基应激和炎症活动的迹象增加,这在肾移植后得到了部分但显著的改善。这些发现表明肾功能在CKD与氧化应激和炎症相关的并发症中的重要性。版权所有(C)2010 S.Karger AG,巴塞尔
Background: Chronic kidney disease (CKD) is characterized by progressive kidney dysfunction accompanied by accumulation of uremic toxins and a potential disequilibrium between the redox status and the generation of prooxidants, resulting in oxidative stress and chronic inflammation which is associated with complications (particularly cardiovascular disease) in this population. We aimed to analyze the concentration of total plasma thiols (indicator of antioxidant capacity) and the protein carbonyl content (a marker of carbonyl stress) in relation to kidney function and inflammation in a group of patients with CKD. Patients and Methods: A group of 68 patients with CKD (stages 2-5; mean age 57 +/- 12 years, 46% male, 34% diabetics) and another group of 21 patients who underwent living donor kidney transplantation (mean age 36 +/- 17 years, 50% male, 10% diabetics, and 9 +/- 2 months after renal transplantation) were included in the study. Total plasma thiol and protein carbonyl levels were determined by the DTNB and DNPH methods, respectively, and were adjusted to the plasma albumin concentrations. Plasma levels of fibrinogen and C-reactive protein (CRP) were measured by routine methods and used as markers of inflammation. Results: Mean glomerular filtration rate (GFR) was 48 ml/min, and there was a positive correlation between GFR and thiol (r = 0.25, p < 0.05) and a negative correlation between GFR and carbonyl (r = -0.26, p < 0.05), fibrinogen (r = -0.45, p < 0.0001) and CRP (r = -0.14, p = ns). Carbonyl strongly correlated with CRP (0.49, p < 0.0001) and fibrinogen (0.30, p < 0.01). There was a significant reduction in plasma carbonyl after renal transplantation (1.4 +/- 0.4 nmol/mg albumin), compared with the levels before the procedure (2.0 +/- 1.4 nmol/mg albumin, p < 0.05), which parallels an improvement in thiol levels (15 +/- 4 vs. 21 +/- 5 nmol/mg albumin, p < 0.001). In addition, there was a significant correlation between CRP and carbonyl after the transplantation (r = 0.65; p < 0.005). Conclusion: We observed that patients with CKD present an altered redox status and increased signs of carbonyl stress and inflammatory activity as kidney function deteriorates, which was partially but significantly improved after renal transplantation. These findings indicate the importance of renal function in the complications of CKD related to oxidative stress and inflammation. Copyright (C) 2010 S. Karger AG, Basel