Yaseelan Palarasah , Rikke Borg , Else-Marie Bladbjerg , Stephanie Thuy Duong Pham , Anna Mejldal , Christian Nielsen , Erik Bo Pedersen , Per Bruno Jensen , Helle Charlotte Thiesson , Katrine Pilely
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引用次数: 0
Abstract
Background and hypothesis
The contact system (CAS) is a part of both the immune system and the coagulation system. The involvement of the CAS in chronic kidney disease (CKD) and hemodialysis (HD) has been documented, yet conflicting findings have hindered a comprehensive understanding. This study aimed to investigate whether CAS activation occurs in patients with chronic kidney failure undergoing HD compared with those undergoing peritoneal dialysis (PD), patients with CKD not receiving replacement therapy, or healthy controls and to assess the impact of HD on CAS from pre- to post-dialysis during a single session of HD.
Methods
In this cross-sectional study, blood samples from HD patients (n = 106), PD patients (n = 40), CKD patients (n = 60), and healthy control subjects (n = 80) were analyzed. The levels of CAS components, including factor XII, prekallikrein, high-molecular-weight kininogen (HK), cleaved HK (cHK), and C1-inhibitor, and functional kallikrein generation were determined. Among HD patients, CAS measures were evaluated both pre- and post-dialysis. Linear regression models and linear mixed models were employed to analyze associations and changes.
Results
HD patients had altered levels of prekallikrein, factor XII, and cHK compared with PD patients, CKD patients, and the healthy control group. Moreover, HD patients demonstrated increased levels of C1-inhibitor and reduced functional kallikrein generation, a pattern also observed in PD patients and, to a lesser degree, in CKD patients when compared with healthy controls. Notably, no CAS activation was detected during HD.
Conclusions
Impaired kidney function, especially in patients undergoing HD or PD, was associated with reduced functional kallikrein generation and altered levels of CAS components, implying continuous CAS activation in CKD. There was no indication of significant activation of factor XII-mediated CAS during HD. The role of CAS in CKD, independently of dialysis, should be addressed in future research.
背景与假设：接触系统（CAS）是免疫系统和凝血系统的一部分。接触系统参与慢性肾脏病（CKD）和血液透析（HD）的研究已有记载，但相互矛盾的研究结果阻碍了对其的全面了解。本研究旨在调查接受血液透析的慢性肾衰竭患者与接受腹膜透析（PD）的患者、未接受替代疗法的慢性肾衰竭患者或健康对照组相比，CAS 是否被激活，并评估在一次血液透析过程中，从透析前到透析后血液透析对 CAS 的影响：在这项横断面研究中，分析了血液透析患者（106 人）、血液透析患者（40 人）、慢性肾脏病患者（60 人）和健康对照组（80 人）的血液样本。测定了CAS成分的水平，包括因子XII、前激肽原、高分子量激肽原（HK）、裂解HK（cHK）和C1-抑制剂，以及功能性激肽原的生成。在血液透析患者中，透析前和透析后都对 CAS 测量进行了评估。采用线性回归模型和线性混合模型分析相关性和变化：结果：与帕金森病患者、慢性肾脏病患者和健康对照组相比，HD 患者的前胰高血糖素、XII因子和 cHK 水平发生了变化。此外，与健康对照组相比，HD 患者的 C1 抑制剂水平升高，功能性allikrein 生成减少，这一模式在 PD 患者中也有观察到，在 CKD 患者中程度较轻。值得注意的是，在血液透析过程中未检测到CAS活化：结论：肾功能受损，尤其是在接受 HD 或 PD 的患者中，与功能性降钙素生成减少和 CAS 成分水平改变有关，这意味着 CAS 在 CKD 中持续活化。在血液透析过程中，没有迹象表明 XII 因子介导的 CAS 被明显激活。未来的研究应关注 CAS 在 CKD 中的作用，而非透析。
期刊介绍：
Thrombosis Research is an international journal dedicated to the swift dissemination of new information on thrombosis, hemostasis, and vascular biology, aimed at advancing both science and clinical care. The journal publishes peer-reviewed original research, reviews, editorials, opinions, and critiques, covering both basic and clinical studies. Priority is given to research that promises novel approaches in the diagnosis, therapy, prognosis, and prevention of thrombotic and hemorrhagic diseases.
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