Beijing Key Laboratory of Diabetes Prevention and Research, Department of Endocrinology, Luhe Hospital, Capital Medical University, Beijing, China.
Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
Nephrol Dial Transplant. 2018 Mar 1;33(3):426-435. doi: 10.1093/ndt/gfx256.
Inflammation is a hallmark of chronic kidney disease (CKD) and stimulates glomerular expression of vascular adhesion molecules (VCAMs). We investigated in a general population whether estimated glomerular filtration rate (eGFR) is associated with circulating adhesion molecules, inflammation markers or both.
We measured serum levels of five adhesion molecules [VCAM-1, intracellular adhesion molecule-1 (ICAM-1), P-selectin, E-selectin and monocyte chemoattractant protein-1 (MCP-1)] and seven inflammation markers [C-reactive protein (CRP), neutrophil gelatinase-associated lipocalin (NGAL), tumour necrosis factor receptor 1 (TNF-R1), TNF-α, interleukin 6 (IL-6), IL-8 and vascular endothelial growth factor] in 1338 randomly recruited people (50.8% women, mean age 51.7 years, eGFR 79.9 mL/min/1.73 m2).
In multivariable-adjusted analyses, eGFR decreased (P ≤ 0.004) with higher VCAM-1 (association size expressed in mL/min/1.73 m2 for a doubling of the marker, -2.99), MCP-1 (-1.19), NGAL (-1.19), TNF receptor 1 (-2.78), TNF-α (-2.28) and IL-6 (-0.94). The odds ratios of having eGFR <60 versus ≥60 mL/min/1.73 m2 (n = 138 versus 1200) were significant (P ≤ 0.001) for VCAM-1 (1.77), MCP-1 (1.32), NGAL (1.26), TNF-R1 (1.49), TNF-α (1.45) and IL-6 (1.20). Compared with 24-h albuminuria, VCAM-1 increased (P <0.0001) the area under the curve from 0.57 to 0.65, MCP-1 to 0.67 and TNF-R1 to 0.79, but TNF-R1 outperformed both adhesion molecules (P < 0.0001).
In a general population, eGFR is inversely associated with circulating adhesion molecules VCAM-1 and MCP-1 and several inflammation markers, but inflammation markers, in particular TNF-R1 and TNF-α, identify patients with eGFR <60 mL/min/1.73 m2 more accurately.
炎症是慢性肾脏病（CKD）的一个标志，并刺激肾小球表达血管细胞黏附分子（VCAMs）。我们在一般人群中研究了估算肾小球滤过率（eGFR）是否与循环黏附分子、炎症标志物或两者都相关。
我们测量了 1338 名随机招募的人的五种黏附分子[VCAM-1、细胞间黏附分子-1（ICAM-1）、P-选择素、E-选择素和单核细胞趋化蛋白-1（MCP-1）]和七种炎症标志物[C 反应蛋白（CRP）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、肿瘤坏死因子受体 1（TNF-R1）、TNF-α、白细胞介素 6（IL-6）、白细胞介素 8（IL-8）和血管内皮生长因子]的血清水平（50.8%为女性，平均年龄 51.7 岁，eGFR 为 79.9 mL/min/1.73 m2）。
在多变量调整分析中，eGFR 随着 VCAM-1（标记物翻倍时以 mL/min/1.73 m2 表示的大小，-2.99）、MCP-1（-1.19）、NGAL（-1.19）、TNF 受体 1（-2.78）、TNF-α（-2.28）和 IL-6（-0.94）的升高而降低（P≤0.004）。与 eGFR≥60 mL/min/1.73 m2（n=138）相比，eGFR<60 mL/min/1.73 m2（n=138）的患者发生 VCAM-1（1.77）、MCP-1（1.32）、NGAL（1.26）、TNF-R1（1.49）、TNF-α（1.45）和 IL-6（1.20）的比值比均显著（P≤0.001）。与 24 小时尿白蛋白相比，VCAM-1 增加（P<0.0001）曲线下面积从 0.57 增加到 0.65，MCP-1 增加到 0.67，TNF-R1 增加到 0.79，但 TNF-R1 优于两种黏附分子（P<0.0001）。
在一般人群中，eGFR 与循环黏附分子 VCAM-1 和 MCP-1 以及几种炎症标志物呈负相关，但炎症标志物，特别是 TNF-R1 和 TNF-α，更能准确地识别 eGFR<60 mL/min/1.73 m2 的患者。
