Short Samuel A P, Wilkinson Katherine, Long D Leann, Crews Deidra C, Gutierrez Orlando M, Irvin Marguerite R, Wheeler Marsha, Cushman Mary, Cheung Katharine L
Department of Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA.
Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, Vermont, USA.
Kidney Int Rep. 2024 May 1;9(7):2016-2027. doi: 10.1016/j.ekir.2024.04.056. eCollection 2024 Jul.
Chronic kidney disease (CKD) is only partly caused by traditional risk factors. Endothelial dysfunction is common in CKD and may contribute to CKD incidence. We studied the association of circulating biomarkers reflecting endothelial dysfunction with incident CKD.
The Reasons for Geographical and Racial Differences in Stroke (REGARDS) study is a prospective cohort of 30,239 Black or White adults aged ≥45 years. Baseline levels of intercellular cellular adhesion molecule 1 (ICAM-1), vascular cellular adhesion molecule 1 (VCAM-1), factor VIII (FVIII), and E-selectin were measured in 3300 participants without baseline CKD or albuminuria who attended a second visit 9.4 years later. Kidney outcomes were incident CKD (estimated glomerular filtration rate [eGFR] <60 ml/min per 1.73 m and ≥40% decline or onset of new end-stage kidney disease), incident ≥30% eGFR decline, and incident albuminuria (albumin-to-creatinine ratio [ACR] ≥30 mg/g). Sequentially adjusted logistic regression models assessed the association of biomarkers with kidney outcomes.
Median age of participants was 62 years, 49% were women, and 46% identified as Black. Of the participants, 228 (6.9%) developed CKD, 613 (18.9%) experienced ≥30% decline in eGFR, and 356 (11.4%) developed albuminuria. The adjusted odds ratios (ORs) for incident CKD per 1 SD increment biomarker was 1.12 for ICAM-1 (95% confidence interval [CI]: 1.02-1.22), 1.10 for VCAM-1 (95% CI: 1.01-1.20), 1.15 for FVIII (95% CI: 1.06-1.24), and 1.10 for E-selectin (95% CI: 1.01-1.20). Results were similar for incident ≥30% eGFR decline but not albuminuria, where only higher FVIII was positively associated.
Higher concentration of ICAM-1, VCAM-1, FVIII, and E-selectin were associated with incident CKD and ≥30% eGFR decline in a large cohort study. Higher FVIII was also associated with incident albuminuria.
慢性肾脏病（CKD）仅部分由传统危险因素引起。内皮功能障碍在CKD中很常见，可能导致CKD的发生。我们研究了反映内皮功能障碍的循环生物标志物与新发CKD之间的关联。
中风地理和种族差异原因（REGARDS）研究是一项针对30239名年龄≥45岁的黑种人或白种成年人的前瞻性队列研究。在3300名无基线CKD或蛋白尿且9.4年后参加第二次随访的参与者中，测量了细胞间黏附分子1（ICAM-1）、血管细胞黏附分子1（VCAM-1）、凝血因子VIII（FVIII）和E-选择素的基线水平。肾脏结局包括新发CKD（估计肾小球滤过率[eGFR]<60 ml/min/1.73 m²且下降≥40%或新发终末期肾病）、新发eGFR下降≥30%以及新发蛋白尿（白蛋白与肌酐比值[ACR]≥30 mg/g）。采用逐步调整的逻辑回归模型评估生物标志物与肾脏结局之间的关联。
参与者的中位年龄为62岁，49%为女性，46%为黑人。在参与者中，228人（6.9%）发生了CKD，613人（18.9%）的eGFR下降≥30%，356人（11.4%）出现了蛋白尿。每增加1个标准差生物标志物，新发CKD的调整优势比（OR）分别为：ICAM-1为1.12（95%置信区间[CI]：1.02-1.22），VCAM-1为1.10（95%CI：1.01-1.20），FVIII为1.15（95%CI：1.06-1.24），E-选择素为1.10（95%CI：1.01-1.20）。新发eGFR下降≥30%的结果相似，但蛋白尿的结果不同，只有较高的FVIII呈正相关。
在一项大型队列研究中，较高浓度的ICAM-1、VCAM-1、FVIII和E-选择素与新发CKD及eGFR下降≥30%相关。较高的FVIII也与新发蛋白尿相关。
