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Updated: Jun 19, 2025
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Changes in the cardiovascular risk profile in children approaching kidney replacement therapy
Priyanka Khandelwal1, Jonas Hofstetter2, Karolis Azukaitis3
1Division of Pediatric Nephrology, UCL Great Ormond Street Hospital and Institute of Child Health, London, UK.
Insights
Cardiovascular damage significantly increases in children with chronic kidney disease (CKD) approaching kidney replacement therapy (KRT). Early intervention targeting modifiable risk factors like blood pressure and BMI can prevent this progressive damage.
Area of Science:
- Pediatric Nephrology
- Cardiovascular Health in CKD
- Chronic Kidney Disease Progression
Background:
- Significant cardiovascular (CV) morbidity is observed in children undergoing dialysis and kidney transplantation.
- However, the evolution of CV damage in children with chronic kidney disease (CKD) before initiating kidney replacement therapy (KRT) remains largely unknown.
Purpose of the Study:
- To explore the burden, progression, and predictors of CV damage in children with CKD in the period leading up to KRT initiation.
- To evaluate the impact of modifiable CV risk factors on CV damage progression.
Main Methods:
- Prospective evaluation of two multicenter cohorts (4C and 3H studies) including 248 children at KRT start and 157 children longitudinally over two years prior to KRT.
- Assessment of CV damage using carotid intima-media thickness (cIMT) standard deviation score (SDS), pulse wave velocity (PWV-SDS), left ventricular (LV) mass, and systolic dysfunction.
- Longitudinal analyses employed mixed-effects models to associate modifiable CV risk factors with changes in CV measures.
Main Results:
- A high prevalence of CV damage was observed at KRT start, including elevated cIMT-SDS (43%), PWV-SDS (25%), LV hypertrophy (49%), and systolic dysfunction (33%).
- Aortic stiffness and LV hypertrophy significantly increased in the year preceding KRT.
- Elevated diastolic blood pressure and BMI were strongly associated with increased CV damage. 79% of children had over three modifiable CV risk factors at KRT onset.
Conclusions:
- Children with CKD experience progressive accrual of CV risk factors and substantial CV damage in the years before KRT.
- This CV damage is largely preventable through early and effective management of modifiable risk factors.
Background:
Despite significant cardiovascular (CV) morbidity in children on dialysis and after kidney transplantation, data on the evolution of CV damage in children with chronic kidney disease (CKD) approaching kidney replacement therapy (KRT) is unknown.
Methods:
The burden, progression, and predictors of CV damage before KRT onset were explored in two prospective multicenter cohorts from Europe and Canada: Cardiovascular Comorbidity in Children with CKD (4C) and Haemodiafiltration, Heart and Height (3H) studies, conducted from 2009-19 and 2013-16, respectively. CV damage and risk factors were evaluated (i) cross sectionally at KRT-start (n = 248), and (ii) longitudinally over the 2-years preceding KRT start (n = 157; 331 patient-visits). Longitudinal analyses with mixed-effects models estimated associations of modifiable CV risk factors with change in carotid intima-media thickness (cIMT) standard deviation score (SDS), pulse wave velocity (PWV-SDS), left ventricular (LV) mass and systolic dysfunction.
Findings:
248 patients, age 14.3 (12.2, 16.2) years were evaluated at median 35 (28-114) days before KRT start. Elevated cIMT-SDS and PWV-SDS were present in 43% and 25%, and LV hypertrophy and systolic dysfunction in 49% and 33%. Aortic stiffness and LV hypertrophy significantly increased, especially in the year before KRT start (adjusted odds ratio, OR 0.33, P = 0.002 and OR 0.54, P = 0.01, respectively). 79% of children had >3 modifiable CV risk factors at KRT onset. Diastolic BP and BMI were strongly associated with a linear increase in all CV measures. After controlling for CV risk factors, the time to KRT onset no longer predicted the burden of CV damage.
Interpretation:
This comprehensive CV evaluation shows the progressive accrual of modifiable risk factors and a high burden of CV damage in the years preceding KRT onset. CV damage in the pre-KRT period is preventable.
Funding:
Supported by EU4Health Programme (101085068) and Kidney Research UK (RP39/2013).
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