血栓调节蛋白与慢性肾脏病严重程度的关联：一项横断面研究。

Association of thrombomodulin with the severity of chronic kidney disease: a cross-sectional study.

作者信息

Guo Ming, Cui Shaoyuan, Liu Xiaoxiao, Feng Jingyi, Li Mengfei, Dong Zheyi, Wu Jie, Cai Guangyan, Chen Xiangmei, Li Qinggang

机构信息

Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases, Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan-vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine (zyyzdxk-2023310), Beijing, 100853, China.

School of Chinese Medicine, Capital Medical University, Beijing, 100069, China.

出版信息

BMC Nephrol. 2025 May 30;26(1):268. doi: 10.1186/s12882-025-04200-5.

DOI:10.1186/s12882-025-04200-5

PMID:40448261

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12123978/

Abstract

BACKGROUND

Inflammatory disorders and endothelial dysfunction are prevalent in patients with chronic kidney disease (CKD). Thrombomodulin (TM) possesses both anticoagulant and anti-inflammatory properties. This study aimed to investigate the association between TM levels and the severity of CKD.

METHODS

This cross-sectional study included two cohorts of patients with CKD from the General Hospital of the Chinese People's Liberation Army. Patients with CKD were categorized into high and low TM groups based on the upper plasma TM reference value. The laboratory indices of patients were compared. Simultaneously, a correlation analysis was performed to identify the association between the TM and each parameter. Patients were categorized into two groups based on eGFR: preserved renal function (eGFR ≥ 60 mL/min/1.73 m²) and significantly impaired renal function (eGFR < 60 mL/min/1.73 m²). Logistic regression analysis and receiver operating characteristic (ROC) curves were used for analysis.

RESULTS

A total of 33 patients with CKD were included in the discovery cohort, and 150 were included in the validation cohort. In the discovery cohort, creatinine (P = 0.0028) and urea nitrogen (P = 0.0011) were significantly higher in the high TM group compared to the low TM group, whereas eGFR (P = 0.0005) was lower. In the validation cohort, high TM group exhibited significantly higher creatinine (P < 0.001), urea nitrogen (P < 0.001), and 24-hour proteinuria levels (P < 0.001) compared to the low TM group, while eGFR (P < 0.001) was lower. Merging the discovery and validation cohorts revealed significant positive correlations between TM and IL-2, TNF-α, vWF (Act), vWF (Ag), serum creatinine, urea nitrogen, and 24-hour proteinuria, while eGFR was negatively correlated with TM (P < 0.001). After adjusting for confounders, TM (adjusted odds ratio = 1.31; 95% CI: 1.10-1.57; P = 0.003) was independently and significantly correlated with CKD severity. Using a TM threshold of > 14.55 TU/ml derived from ROC analysis for severity stratification, the AUC was 0.7739 (95% CI: 0.71-0.84) in differentiating CKD severity stages.

CONCLUSION

Serum TM levels demonstrated a significant correlation with CKD severity, suggesting its potential as a biomarker with clinical utility for CKD staging.

CLINICAL TRIAL NUMBER

Not applicable.

摘要

背景

炎症性疾病和内皮功能障碍在慢性肾脏病（CKD）患者中普遍存在。血栓调节蛋白（TM）具有抗凝和抗炎特性。本研究旨在探讨TM水平与CKD严重程度之间的关联。

方法

这项横断面研究纳入了中国人民解放军总医院的两组CKD患者队列。根据血浆TM参考值上限，将CKD患者分为高TM组和低TM组。比较患者的实验室指标。同时，进行相关性分析以确定TM与各参数之间的关联。根据估算肾小球滤过率（eGFR）将患者分为两组：肾功能保留（eGFR≥60 mL/min/1.73 m²）和肾功能显著受损（eGFR＜60 mL/min/1.73 m²）。采用逻辑回归分析和受试者工作特征（ROC）曲线进行分析。

结果

发现队列共纳入33例CKD患者，验证队列纳入150例。在发现队列中，高TM组的肌酐（P = 0.0028）和尿素氮（P = 0.0011）显著高于低TM组，而eGFR（P = 0.0005）较低。在验证队列中，高TM组的肌酐（P＜0.001）、尿素氮（P＜0.001）和24小时蛋白尿水平（P＜0.001）显著高于低TM组，而eGFR（P＜0.001）较低。合并发现队列和验证队列后发现，TM与白细胞介素-2、肿瘤坏死因子-α、血管性血友病因子（Act）、血管性血友病因子（Ag）、血清肌酐、尿素氮和24小时蛋白尿呈显著正相关，而eGFR与TM呈负相关（P＜0.001）。在调整混杂因素后，TM（调整比值比 = 1.31；95%置信区间：1.10 - 1.57；P = 0.003）与CKD严重程度独立且显著相关。使用ROC分析得出的＞14.55 TU/ml的TM阈值进行严重程度分层，在区分CKD严重程度阶段时，曲线下面积（AUC）为0.7739（95%置信区间：0.71 - 0.84）。