Phan Trung, Mcmillan Ryan, Skiadopoulos Leonidas, Walborn Amanda, Hoppensteadt Debra, Fareed Jawed, Bansal Vinod
Stritch School of Medicine, Loyola University of Chicago, Maywood, IL, USA.
Unit of Hemostasis and Thrombosis, Department of Pathology, Loyola University Medical Center, Maywood, IL, USA.
Int Angiol. 2018 Oct;37(5):419-426. doi: 10.23736/S0392-9590.18.03987-1. Epub 2018 Apr 11.
Chronic kidney disease is a disorder characterized by a pro-inflammatory state that is associated with increased morbidity and mortality. Endogenous damage-associated molecular patterns, including nucleosomes, may contribute to this persistent inflammation. The aim of this study was to profile and evaluate the clinical significance of circulating nucleosomes in patients with Stage 5 chronic kidney disease (CKD5) on hemodialysis (HD).
Under institutional review board approval, plasma samples were collected from 90 CKD5-HD patients (45 male and 45 female) prior to hemodialysis. Normal human plasma samples (25 male and 25 female) were used as a control group. Commercial enzyme-linked immunosorbent and colorimetric assays were used to profile nucleosome levels and biochemical markers of kidney injury, inflammation, thrombosis, and renal function in CKD5-HD and control groups. Clinical laboratory parameters were documented from the electronical medical record and correlated to nucleosome levels in the CKD5-HD cohort.
In comparison to healthy volunteers, the plasma from CKD5-HD patients exhibited markedly elevated nucleosomes (P<0.0001). Furthermore, nucleosome levels correlated with WBC count (P=0.025, R=0.243) and CRP (P=0.019, R=0.266) levels. No correlation was found between nucleosomes and the other parameters studied.
Our findings indicate extracellular nucleosomes are significantly elevated in CKD5-HD, suggesting increased cell death and/or inflammation. The observed correlations between nucleosomes and parameters of inflammation is suggestive of a complex, systemic inflammatory process underlying renal deterioration, consistent with the literature. Thus, nucleosomes may play a role in the pathogenesis and outcome of CKD5-HD.
慢性肾脏病是一种以促炎状态为特征的疾病，与发病率和死亡率增加相关。包括核小体在内的内源性损伤相关分子模式可能导致这种持续性炎症。本研究的目的是分析和评估接受血液透析（HD）的5期慢性肾脏病（CKD5）患者循环核小体的特征及其临床意义。
在机构审查委员会批准下，于血液透析前从90例CKD5-HD患者（45例男性和45例女性）采集血浆样本。正常人类血浆样本（25例男性和25例女性）用作对照组。使用商业酶联免疫吸附和比色测定法分析CKD5-HD组和对照组中核小体水平以及肾损伤、炎症、血栓形成和肾功能的生化标志物。从电子病历中记录临床实验室参数，并与CKD5-HD队列中的核小体水平相关联。
与健康志愿者相比，CKD5-HD患者的血浆中核小体水平显著升高（P<0.0001）。此外，核小体水平与白细胞计数（P=0.025，R=0.243）和CRP（P=0.019，R=0.266）水平相关。未发现核小体与其他研究参数之间存在相关性。
我们的研究结果表明，CKD5-HD患者细胞外核小体显著升高，提示细胞死亡和/或炎症增加。观察到的核小体与炎症参数之间的相关性表明，肾脏恶化背后存在复杂的全身性炎症过程，这与文献一致。因此，核小体可能在CKD5-HD的发病机制和结局中起作用。
