Centre for Family Medicine, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden;
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden;
J Am Soc Nephrol. 2014 Jun;25(6):1313-20. doi: 10.1681/ASN.2013080860. Epub 2014 Feb 7.
The importance of TNF-α and its soluble receptors (sTNFR1 and sTNFR2) in the development of kidney disease is being unraveled. Yet, community-based data regarding the role of sTNFRs are lacking. We assessed serum sTNFRs and aspects of kidney damage cross-sectionally in two independent community-based cohorts of elderly participants: Prospective Investigation of the Vasculature in Uppsala Seniors (n=815; mean age, 75 years; 51% women) and Uppsala Longitudinal Study of Adult Men (n=778; mean age, 78 years). Serum sTNFR1 correlated substantially with different aspects of kidney pathology in the Uppsala Longitudinal Study of Adult Men cohort (R=-0.52 for estimated GFR, R=0.22 for urinary albumin-to-creatinine ratio, and R=0.17 for urinary kidney injury molecule-1; P<0.001 for all), with similar correlations in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort. These associations remained significant after adjustment for age, sex, inflammatory markers, and cardiovascular risk factors and were also evident in participants without diabetes. Serum sTNFR2 was associated with all three markers in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort (P<0.001 for all). Our findings from two independent community-based cohorts confirm and extend results of previous studies supporting circulating sTNFRs as relevant biomarkers for kidney damage and dysfunction in elderly individuals, even in the absence of diabetes.
TNF-α 及其可溶性受体（sTNFR1 和 sTNFR2）在肾脏疾病发展中的重要性正在被揭示。然而，关于 sTNFR 在社区中的作用的数据还很缺乏。我们在两个独立的老年人社区队列中对血清 sTNFRs 和肾脏损伤的各个方面进行了横断面评估：乌普萨拉老年人血管前瞻性研究（n=815；平均年龄 75 岁；51%为女性）和乌普萨拉成年男性纵向研究（n=778；平均年龄 78 岁）。血清 sTNFR1 与乌普萨拉成年男性纵向研究队列中肾脏病理的不同方面密切相关（估计肾小球滤过率为 R=-0.52，尿白蛋白/肌酐比值为 R=0.22，尿肾损伤分子-1 为 R=0.17；所有 P<0.001），在血管前瞻性研究中的老年人群中也存在类似的相关性。在调整年龄、性别、炎症标志物和心血管危险因素后，这些相关性仍然显著，在没有糖尿病的参与者中也存在这些相关性。血清 sTNFR2 与血管前瞻性研究中的所有三个标志物相关（所有 P<0.001）。我们从两个独立的社区队列中得到的发现证实并扩展了之前的研究结果，表明循环 sTNFRs 是老年人群中肾脏损伤和功能障碍的相关生物标志物，即使在没有糖尿病的情况下也是如此。
