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Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Association of thrombomodulin with the severity of chronic kidney disease: a cross-sectional study
Ming Guo1, Shaoyuan Cui1, Xiaoxiao Liu1
1Department 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.
Insights
Thrombomodulin (TM) levels correlate with chronic kidney disease (CKD) severity. Higher TM indicates more severe CKD, suggesting TM as a potential biomarker for staging this condition.
Area of Science:
- Nephrology
- Biochemistry
- Clinical Medicine
Background:
- Chronic kidney disease (CKD) is linked to inflammation and endothelial dysfunction.
- Thrombomodulin (TM) exhibits anticoagulant and anti-inflammatory properties.
- Investigating TM's role in CKD progression is crucial.
Purpose of the Study:
- To determine the association between plasma Thrombomodulin (TM) levels and the severity of chronic kidney disease (CKD).
- To evaluate TM as a potential biomarker for CKD staging.
Main Methods:
- Cross-sectional study with discovery (33 patients) and validation (150 patients) cohorts.
- Categorization into high and low TM groups based on plasma TM levels.
- Correlation analysis and logistic regression to assess TM's association with CKD parameters and severity, including eGFR, creatinine, urea nitrogen, and proteinuria. ROC curves were used for analysis.
Main Results:
- Higher TM levels correlated with increased creatinine, urea nitrogen, and 24-hour proteinuria, and decreased eGFR in both cohorts.
- TM showed significant positive correlations with inflammatory markers (IL-2, TNF-α) and endothelial dysfunction markers (vWF).
- Adjusted logistic regression confirmed TM as an independent predictor of CKD severity (aOR=1.31, P=0.003), with an ROC AUC of 0.7739 for staging.
Conclusions:
- Serum TM levels are significantly correlated with CKD severity.
- TM shows potential as a valuable biomarker for clinical utility in CKD staging.
- Further research can explore TM's therapeutic implications in managing CKD.
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.
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