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Updated: Mar 12, 2026
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Cardiovascular Phenotypes in Children with CKD: The 4C Study
Franz Schaefer1, Anke Doyon, Karolis Azukaitis
1Due to the number of contributing authors, the affiliations are provided in the Supplemental Material .
Insights
Cardiovascular disease is a major concern for children with chronic kidney disease (CKD). This study found that high blood pressure and CKD stage are linked to markers of heart disease in pediatric patients.
Area of Science:
- Pediatric Nephrology
- Cardiovascular Research
- Public Health
Background:
- Cardiovascular disease (CVD) is a critical comorbidity impacting survival in pediatric patients with chronic kidney disease (CKD).
- Early identification and monitoring of cardiovascular risk factors are essential for improving long-term outcomes in this vulnerable population.
Purpose of the Study:
- To investigate the prevalence of subclinical cardiovascular disease markers in children with CKD.
- To explore the association between these markers and clinical factors such as hypertension and CKD stage.
Main Methods:
- A multicenter, prospective, observational study involving 688 children aged 6-17 years with CKD (GFR 10-60 ml/min/1.73 m²).
- Annual monitoring of cardiovascular status using noninvasive surrogate markers: left ventricular mass index, carotid intima-media thickness, and pulse wave velocity.
- Exploratory analysis of variables associated with cardiovascular surrogate markers at baseline.
Main Results:
- A high prevalence of cardiovascular risk factors was observed: 26.1% had uncontrolled hypertension, increasing with CKD stage.
- Left ventricular hypertrophy was present in 10.6% (CKD stage 3a) to 48% (CKD stage 5).
- Elevated carotid intima-media thickness (41.6%) and increased pulse wave velocity (20.1%) were common. Office systolic blood pressure SD score was independently associated with all surrogate markers.
Conclusions:
- Baseline data from a large pediatric cohort reveal a strong association between cardiovascular disease surrogate markers and systolic hypertension.
- The stage of chronic kidney disease is also closely linked to these cardiovascular indicators in children.
- These findings underscore the importance of managing hypertension and monitoring cardiovascular health in pediatric CKD patients.
Background And Objectives:
Cardiovascular disease is the most important comorbidity affecting long-term survival in children with CKD.
Design, Setting, Participants, & Measurements:
The Cardiovascular Comorbidity in Children with CKD Study is a multicenter, prospective, observational study in children ages 6-17 years old with initial GFR of 10-60 ml/min per 1.73 m2. The cardiovascular status is monitored annually, and subclinical cardiovascular disease is assessed by noninvasive measurements of surrogate markers, including the left ventricular mass index, carotid intima-media thickness, and central pulse wave velocity. We here report baseline data at study entry and an explorative analysis of variables associated with surrogate markers.
Results:
A total of 737 patients were screened from October of 2009 to August of 2011 in 55 centers in 12 European countries, and baseline data were analyzed in 688 patients. Sixty-four percent had congenital anomalies of the kidney and urinary tract; 26.1% of children had uncontrolled hypertension (24-hour ambulatory BP monitoring; n=545), and the prevalence increased from 24.4% in CKD stage 3 to 47.4% in CKD stage 5. The prevalence of left ventricular hypertrophy was higher with each CKD stage, from 10.6% in CKD stage 3a to 48% in CKD stage 5. Carotid intima-media thickness was elevated in 41.6%, with only 10.8% of patients displaying measurements below the 50th percentile. Pulse wave velocity was increased in 20.1%. The office systolic BP SD score was the single independent factor significantly associated with all surrogate markers of cardiovascular disease. The intermediate end point score (derived from the number of surrogate marker measurements >95th percentile) was independently associated with a diagnosis of congenital anomalies of the kidney and urinary tract, time since diagnosis of CKD, body mass index, office systolic BP, serum phosphorus, and the hemoglobin level.
Conclusions:
The baseline data of this large pediatric cohort show that surrogate markers for cardiovascular disease are closely associated with systolic hypertension and stage of CKD.
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