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.