Lindblad Ylva Tranæus, Tóthová Ľubomíra, Celec Peter, Kublickiene Karolina, Bárány Peter, Chromek Milan
Division of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Institute of Molecular Biomedicine, Comenius University Medical School, Bratislava, Slovakia.
Sci Rep. 2025 Jan 21;15(1):2645. doi: 10.1038/s41598-025-86857-4.
Chronic kidney disease (CKD) is associated with chronic low-grade inflammation, but the primary factors triggering this inflammation remain unclear. Extracellular or cell-free DNA (exDNA) originates from virtually all tissues, being released during cell death, and stimulates the innate immune system. Our study was designed as an observational, cross-sectional cohort study of children with CKD (both before and after kidney transplantation) and controls to analyze associations between exDNA, markers of inflammation, and cardiovascular health. Extracellular DNA (total, nuclear, and mitochondrial) was analyzed in plasma using fluorometry and real-time PCR. We found that children with CKD after kidney transplantation had higher concentrations of total and nuclear extracellular DNA (total exDNA and nc_exDNA) in plasma compared to controls. In univariate analysis, levels of interleukin-6 (IL-6), antimicrobial peptide cathelicidin (LL-37), soluble vascular cell adhesion molecule-1 (VCAM-1) and left ventricular mass index (LVMI) were positively correlated with total exDNA and nc_exDNA concentrations. Multivariate analysis revealed LVMI as the only independent variable associated with high levels of both total exDNA and nc_exDNA. We believe that our results contribute new knowledge to the pathogenesis of CKD and its complications and may help identify new treatment targets.
慢性肾脏病（CKD）与慢性低度炎症相关，但引发这种炎症的主要因素仍不清楚。细胞外或无细胞DNA（exDNA）几乎源自所有组织，在细胞死亡期间释放，并刺激先天免疫系统。我们的研究设计为一项观察性横断面队列研究，研究对象为CKD患儿（肾移植前后）及对照组，以分析exDNA、炎症标志物与心血管健康之间的关联。使用荧光测定法和实时聚合酶链反应分析血浆中的细胞外DNA（总DNA、核DNA和线粒体DNA）。我们发现，肾移植后的CKD患儿血浆中总细胞外DNA和核细胞外DNA（总exDNA和nc_exDNA）的浓度高于对照组。在单变量分析中，白细胞介素-6（IL-6）、抗菌肽cathelicidin（LL-37）、可溶性血管细胞粘附分子-1（VCAM-1）和左心室质量指数（LVMI）水平与总exDNA和nc_exDNA浓度呈正相关。多变量分析显示LVMI是与总exDNA和nc_exDNA高水平相关的唯一独立变量。我们相信，我们的结果为CKD及其并发症的发病机制贡献了新知识，并可能有助于确定新的治疗靶点。
