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在慢性肾脏病分期中的炎症生物标志物:升高的 TNFR2 水平伴随着肾功能下降。

Inflammatory biomarkers in staging of chronic kidney disease: elevated TNFR2 levels accompanies renal function decline.

机构信息

UCIBIO - Applied Molecular Biosciences Unit, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Rua Jorge de Viterbo Ferreira 228, E2, P5, 4050-313, Porto, Portugal.

Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal.

出版信息

Inflamm Res. 2022 Jun;71(5-6):591-602. doi: 10.1007/s00011-022-01574-2. Epub 2022 Apr 26.

Abstract

BACKGROUND

Inflammation is a common feature in the pathogenesis of chronic kidney disease (CKD), regardless of the disease cause. Our aim was to evaluate the potential of several inflammatory biomarkers in CKD diagnosis and staging.

METHODS

A total of 24 healthy controls and 92 pre-dialysis CKD patients with diverse etiologies, were enrolled in this study and grouped according to their CKD stage. We analysed the circulating levels of inflammatory molecules, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), tumor necrosis factor receptor 2 (TNFR2), pentraxin 3 (PTX3) and leptin, as well as the hemogram. We studied their association with parameters of kidney function and kidney injury, to evaluate their potential as early markers of the disease and/or of its worsening, as well as their interplay.

RESULTS

Compared to controls, patients in CKD stages 1-2 presented significantly higher IL-6 and TNFR2 levels, and higher neutrophil-to-lymphocyte ratio. All inflammatory cytokines and acute-phase proteins showed a trend to increase up to stage 3, stabilizing or declining thereafter, save for TNFR2, which steadily increased from stage to stage. All inflammatory molecules, apart from PTX3, were negatively and significantly correlated with eGFR, with a remarkable value for TNFR2 (r = - 0.732, p < 0.001).

CONCLUSION

TNFR2 might be useful for an early detection of CKD, as well as for disease staging/worsening. Still, the potential value of this biomarker in disease progression warrants further investigation.

摘要

背景

炎症是慢性肾脏病(CKD)发病机制中的一个共同特征,与疾病原因无关。我们的目的是评估几种炎症生物标志物在 CKD 诊断和分期中的潜力。

方法

本研究共纳入 24 名健康对照者和 92 名病因不同的透析前 CKD 患者,并根据 CKD 分期进行分组。我们分析了循环炎症分子、C 反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、肿瘤坏死因子受体 2(TNFR2)、五聚素 3(PTX3)和瘦素的水平,以及血常规。我们研究了它们与肾功能和肾脏损伤参数的关系,以评估它们作为疾病早期标志物和/或疾病恶化的标志物的潜力,以及它们的相互作用。

结果

与对照组相比,CKD 1-2 期患者的 IL-6 和 TNFR2 水平显著升高,中性粒细胞与淋巴细胞比值升高。所有炎症细胞因子和急性期蛋白的水平均呈上升趋势,直至 3 期,此后趋于稳定或下降,除 TNFR2 外,TNFR2 从一期到三期持续升高。除 PTX3 外,所有炎症分子均与 eGFR 呈显著负相关,TNFR2 的相关性最强(r=-0.732,p<0.001)。

结论

TNFR2 可能有助于早期发现 CKD 以及疾病分期/恶化。然而,该生物标志物在疾病进展中的潜在价值仍需进一步研究。

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