Related Experiment Video
Updated: Jan 20, 2026
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Indoxyl sulfate associates with cardiovascular phenotype in children with chronic kidney disease
Johannes Holle1, Uwe Querfeld2, Marietta Kirchner3
1Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. johannes-benjamin.holle@charite.de.
Insights
In children with chronic kidney disease (CKD), serum levels of indoxyl sulfate (IS) and p-cresyl sulfate (pCS) were measured. Only IS showed significant associations with cardiovascular disease markers.
Area of Science:
- Pediatric Nephrology
- Cardiovascular Research
- Toxicology
Background:
- Cardiovascular disease is a primary cause of mortality in pediatric chronic kidney disease (CKD).
- Gut-derived uremic toxins, such as indoxyl sulfate (IS) and p-cresyl sulfate (pCS), accumulate as kidney function declines.
- Elevated toxin levels are linked to cardiac issues in adult CKD patients.
Purpose of the Study:
- To investigate the association between serum levels of IS and pCS and cardiovascular disease markers in children with CKD.
- To determine the relationship between these toxins and estimated glomerular filtration rate (eGFR) in the pediatric CKD population.
Main Methods:
- Serum concentrations of IS and pCS were quantified using high-performance liquid chromatography in 609 children (aged 6-17 years) with CKD (eGFR 10-60 ml/min/1.73 m²).
- Cardiovascular parameters including carotid intima-media thickness (cIMT), pulse wave velocity (PWV), and left ventricular mass index (LVMI) were assessed.
- Multivariable regression models were employed to analyze associations between toxin levels, eGFR, and cardiovascular markers.
Main Results:
- Median serum levels for total IS and pCS were 5.3 μmol/l and 17.0 μmol/l, respectively.
- Both IS and pCS showed positive correlations with urea and negative correlations with eGFR.
- Indoxyl sulfate (IS) was significantly associated with increased carotid intima-media thickness (cIMT) and progression of pulse wave velocity (PWV), independent of other risk factors.
Conclusions:
- Serum IS and pCS levels are inversely related to eGFR in children with CKD.
- Indoxyl sulfate (IS) is the primary gut-derived uremic toxin associated with surrogate markers of cardiovascular disease in this pediatric cohort.
Background:
Cardiovascular disease is the leading cause of death in children with chronic kidney disease (CKD). Serum levels of gut-derived uremic toxins increase with deterioration of kidney function and are associated with cardiac comorbidities in adult CKD patients.
Methods:
Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) were measured by high-performance liquid chromatography in serum of children participating in the Cardiovascular Comorbidity in Children with CKD (4C) Study. Results were correlated with measurements of the carotid intima-media thickness (cIMT), central pulse wave velocity (PWV), and left ventricular mass index (LVMI) in children aged 6-17 years with initial eGFR of 10-60 ml/min per 1.73 m2.
Results:
The median serum levels of total IS and of pCS, measured in 609 patients, were 5.3 μmol/l (8.7) and 17.0 μmol/l (21.6), respectively. In a multivariable regression model, IS and pCS showed significant positive associations with urea and negative associations with eGFR and uric acid. Furthermore, positive associations of pCS with age, serum albumin, and non-Mediterranean residency and a negative association with glomerular disease were observed. By multivariable regression analysis, only IS was significantly associated with a higher cIMT SDS at baseline and progression of PWV SDS within 12 months, independent of other risk factors.
Conclusions:
Serum levels of gut-derived uremic toxins IS and pCS correlated inversely with eGFR in children. Only IS was significantly associated with surrogate markers of cardiovascular disease in this large pediatric CKD cohort.
Related Concept Videos
01:25Chronic Kidney Disease I: Introduction
01:24Chronic Kidney Disease II: Clinical Manifestations
01:28Chronic Kidney Disease III: Interprofessional Care
01:18Chronic Kidney Disease IV: Nursing Management
01:27Psychoneuroimmunology: Cardiovascular Disease
A key area of focus in PNI is the relationship between stress and coronary...
01:22Chronic Obstructive Pulmonary Disease
Smoking is a primary risk factor for COPD, with over 80% of patients having a history of it. Patients typically experience progressive dyspnea or labored breathing, frequent coughing, and recurrent pulmonary infections. Many eventually succumb to respiratory failure, characterized by...