Association of Angiopoietin-2 with Renal Outcome in Chronic Kidney Disease

BackgroundThe pathophysiological mechanisms of renal function progression in chronic kidney disease (CKD) have still not been completely explored. In addition to well-known traditional risk factors, non-traditional risk factors, such as endothelial dysfunction, have gradually attracted physicians' attention. Angiopoietin-2 (Ang-2) impairs endothelial function through preventing angiopoietin-1 from binding to Tie2 receptor. Whether Ang-2 is associated with renal function progression in CKD is unknown.MethodsThis study enrolled 621 patients with stages 3–5 CKD to assess the association of circulating Ang-2 with commencing dialysis, doubling creatinine and rapid decline in renal function (the slope of estimated glomerular filtration rate (eGFR) greater than 5 ml/min per 1.73 m2/y) over follow-up of more than 3 years.ResultsOf all patients, 224 patients (36.1%) progressed to commencing dialysis and 165 (26.6%) reached doubling creatinine. 85 subjects (13.9%) had rapid decline in renal function. Ang-2 quartile was divided at 1494.1, 1948.8, and 2593.1 pg/ml. The adjusted HR of composite outcomes, either commencing dialysis or doubling creatinine was 1.53 (95% CI: 1.06–2.23) for subjects of quartile 4 compared with those of quartile 1. The adjusted OR for rapid decline in renal function was 2.96 (95% CI: 1.13–7.76) for subjects of quartile 4 compared with those of quartile 1. The linear mixed-effects model shows a more rapid decrease in eGFR over time in patients with quartile 3 or more of Ang-2 than those with the lowest quartile of Ang-2.ConclusionsAng-2 is an independent predictor of adverse renal outcome in CKD. Further study is needed to identify the pathogenic role of Ang-2 in CKD progression.背景：慢性肾脏病（Chronic Kidney Disease, CKD）患者肾功能进展的病理生理机制尚未完全阐明。除公认的传统危险因素外，内皮功能障碍（endothelial dysfunction）等非传统危险因素逐渐受到临床医师的关注。血管生成素-2（Angiopoietin-2, Ang-2）可通过阻碍血管生成素-1与Tie2受体结合而损害内皮功能。目前尚不明确血管生成素-2是否与慢性肾脏病患者的肾功能进展相关。 方法：本研究纳入621例CKD 3~5期患者，以评估循环血管生成素-2与随访时长超过3年期间，患者开始透析治疗、肌酐翻倍及肾功能快速下降（估算肾小球滤过率（estimated glomerular filtration rate, eGFR）斜率＞5 ml·min⁻¹·1.73m⁻²·y⁻¹）的相关性。 结果：入组患者中，224例（36.1%）进展至需开始透析治疗，165例（26.6%）出现肌酐翻倍；另有85例（13.9%）发生肾功能快速下降。血管生成素-2的四分位数切点分别为1494.1、1948.8及2593.1 pg/ml。与四分位数1组相比，四分位数4组患者的复合终点（开始透析或肌酐翻倍）校正后风险比（hazard ratio, HR）为1.53（95%置信区间（confidence interval, 95% CI）：1.06~2.23）。与四分位数1组相比，四分位数4组患者肾功能快速下降的校正后比值比（odds ratio, OR）为2.96（95%置信区间：1.13~7.76）。线性混合效应模型分析显示，血管生成素-2四分位数3及以上的患者，其eGFR随时间下降的速度显著高于四分位数最低组患者。 结论：血管生成素-2可作为慢性肾脏病患者不良肾脏结局的独立预测因子。未来仍需进一步研究以明确血管生成素-2在慢性肾脏病进展中的致病作用。