OBJECTIVE To determine whether biomarkers of inflammation and endothelial dysfunction are associated with the development of kidney dysfunction and the time frame of their association. RESEARCH DESIGN AND METHODS Biomarkers were measured at four time points during 28 years of treatment and follow-up in patients with type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. In addition to traditional biomarkers of inflammation (C-reactive protein and fibrinogen), we measured interleukin-6 (IL-6) and soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1/2), markers of endothelial dysfunction (soluble intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin [sE-selectin]), and fibrinolysis (total and active plasminogen activator inhibitor-1 [PAI-1]). Renal outcomes were defined as progression to incident chronic kidney disease (stage 3 or more severe) or macroalbuminuria (albumin excretion rate ≥300 mg/24 h). Prospective multivariate event-time analyses were used to determine the association of each biomarker with each subsequent event within prespecified intervals (3-year and 10-year windows). RESULTS Multivariate event-time models indicated that several markers of inflammation (sTNFR-1/2), endothelial dysfunction (sE-selectin), and clotting/fibrinolysis (fibrinogen and PAI-1) are significantly associated with subsequent development of kidney dysfunction. Although some markers showed variations in the associations between the follow-up windows examined, the results indicate that biomarkers (sTNFR-1/2, sE-selectin, PAI-1, and fibrinogen) are associated with progression to chronic kidney disease in both the 3-year and the 10-year windows. CONCLUSIONS Plasma markers of inflammation, endothelial dysfunction, and clotting/fibrinolysis are associated with progression to kidney dysfunction in type 1 diabetes during both short-term and long-term follow-up.

中文翻译：

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炎症标志物与肾功能不全之间的关联：检查1型糖尿病患者的不同评估窗口。

目的确定炎症和内皮功能障碍的生物标志物是否与肾脏功能障碍的发生及其相关的时限有关。研究设计与方法在糖尿病控制与并发症试验/糖尿病干预与并发症流行病学（DCCT / EDIC）队列中，在28年的治疗和随访期间的1个糖尿病患者中的四个时间点对生物标志物进行了测量。除了传统的炎症生物标志物（C反应蛋白和纤维蛋白原）外，我们还测量了白细胞介素6（IL-6）和可溶性肿瘤坏死因子受体1和2（sTNFR-1 / 2），它们是内皮功能障碍的标志物（可溶性细胞内粘附分子-1，血管细胞粘附分子-1和E-选择素[sE-selectin]），和纤维蛋白溶解（总的和活性的纤溶酶原激活物抑制剂1 [PAI-1]）。肾结局定义为进展为慢性肾脏疾病（3级或以上）或大白蛋白尿（白蛋白排泄率≥300mg / 24 h）。使用前瞻性多元事件时间分析来确定每个生物标记物与预先确定的时间间隔（3年和10年窗口）内每个后续事件的关联。结果多元事件时间模型表明，炎症的一些标志物（sTNFR-1 / 2），内皮功能障碍（sE-选择素）和凝血/纤维蛋白溶解（纤维蛋白原和PAI-1）与随后的肾功能障碍显着相关。尽管某些标记物显示了所检查的随访窗口之间的关联存在差异，但结果表明，生物标记物（sTNFR-1 / 2，sE-选择素，PAI-1和纤维蛋白原在3年和10年期间均与慢性肾脏病的进展有关。结论在短期和长期随访中，炎症，内皮功能障碍和凝血/纤维蛋白溶解的血浆标志物与1型糖尿病患者肾功能障碍的进展有关。