Related Experiment Video
Updated: Jan 15, 2026
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Endothelin-1 as dual marker for renal function decline and associated cardiovascular complications in patients with
Laura González-Rodríguez1, Manuel Martí-Antonio2, Sonia Mota-Zamorano3
1Department of Medical and Surgical Therapeutics, Medical School, Universidad de Extremadura, 06006 Badajoz, Spain; RICORS2040 Renal Research Network, 2802940 Madrid, Spain.
Insights
Endothelin-1 (ET-1) is linked to worsening chronic kidney disease (CKD) and cardiovascular events. Measuring ET-1 may help predict kidney decline and heart risks in CKD patients.
Area of Science:
- Nephrology
- Cardiology
- Biomarker Discovery
Background:
- Cardiovascular complications are the primary cause of mortality in chronic kidney disease (CKD) patients.
- Endothelin-1 (ET-1), a vasoconstrictor implicated in renal and vascular dysfunction, is a potential biomarker for CKD progression and cardiovascular disease (CVD).
Purpose of the Study:
- To investigate the association between plasma Endothelin-1 (ET-1) levels and the progression of chronic kidney disease (CKD).
- To evaluate ET-1 as a predictive biomarker for cardiovascular events (CVE) and all-cause mortality in CKD patients.
Main Methods:
- Quantified ET-1 plasma levels in 692 Spanish CKD patients (stages 1-5).
- Stratified patients into three clusters based on ET-1 concentrations.
- Assessed associations with CKD progression, CVE, and mortality using mixed-effects models and Cox regression over a mean follow-up of 48.6 months, adjusting for conventional risk factors.
Main Results:
- ET-1 levels significantly increased with CKD severity (p < 0.001).
- Higher ET-1 levels were independently associated with accelerated estimated glomerular filtration rate (eGFR) decline over 3 years (p < 0.001 for cluster 2; p = 0.034 for cluster 3).
- Elevated ET-1 independently predicted cardiovascular events (HR = 2.24, p = 0.022 for cluster 2; HR = 2.50, p = 0.03 for cluster 3) and all-cause mortality (p < 0.001).
- Random forest models incorporating ET-1 clusters showed high predictive accuracy for CV risk (C-index = 0.835) and all-cause mortality (C-index = 0.837).
Conclusions:
- Elevated ET-1 levels are significantly and independently associated with both CKD progression and cardiovascular complications.
- ET-1 demonstrates potential as a dual biomarker for predicting renal deterioration and cardiovascular risk in CKD patients.
- ET-1 may enhance clinical stratification and management strategies for individuals with chronic kidney disease.
Background:
Cardiovascular (CV) complications are the leading cause of death in patients with chronic kidney disease (CKD). Endothelin-1 (ET-1), a potent vasoconstrictor involved in both renal and vascular dysfunction, may represent a promising biomarker for the disease.
Methods:
ET-1 plasma levels were quantified in 692 Spanish CKD patients (stages 1-5) and used to stratify individuals into three clusters (cluster 3 meaning highest concentrations). Associations with CKD progression, CVE, and all-cause mortality were assessed over a mean follow-up of 48.6 ± 27.4 months using linear mixed-effects models and Cox regression analyses adjusted for conventional risk factors.
Results:
ET-1 levels increased with CKD severity (mean±SD: 1.65 ± 0.71 pg/mL for stages 1-2; 1.82 ± 0.71 pg/mL for stage 3; 2.39 ± 1.08 pg/mL for stages 4-5; p < 0.001). Higher ET-1 levels were independently associated with accelerated eGFR decline over 3 years (β = -12.64, p < 0.001 for cluster 2; and β = -11.71, p = 0.034 for cluster 3). Sixty-nine CVE (10.1 %) were recorded. Participants with higher ET-1 levels had significantly lower CV event-free survival [HR = 2.24 (1.12-4.45), p = 0.022, and HR = 2.50 (1.09-5.73), p = 0.03] for clusters 2 and 3, respectively. ET-1 also predicted all-cause mortality (p < 0.001) although the association lost significance after adjusting for age. Random forest models for CV risk and all-cause mortality including the ET-1 cluster produced C-indices of 0.835 and 0.837, respectively.
Conclusions:
Elevated ET-1 levels are independently associated with both CKD progression and CV complications. ET-1 may serve as a dual biomarker for renal deterioration and CV risk, potentially improving clinical stratification in CKD management.
Related Concept Videos
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
01:25Chronic Kidney Disease I: Introduction
01:24Chronic Kidney Disease II: Clinical Manifestations
01:28Drug Dosing in Renal Diseases: Estimation of Glomerular Filtration Rate Based on Serum Creatinine Concentration
01:29Heart Failure II: Pathophysiology
01:17Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...