Progression of Carotid Intima-Media Thickness in Children of the Cardiovascular Comorbidity in Children With Chronic Kidney Disease Study: Risk Factors and Impact of Blood Pressure Dynamics

Abstract

Background: Carotid intima-media thickness (cIMT) may identify early alterations in the vascular phenotype in children with chronic kidney disease (CKD).

Methods and results: Investigation of longitudinal changes in cIMT SD scores (SDS) in 670 patients from the 4C Study (Cardiovascular Comorbidity in Children With CKD Study), aged 6 to 17 years, with CKD stage 3 to 5 at baseline. The longitudinal trajectory of cIMT SDS over up to 8 years was examined using a longitudinal mixed-effects model. The yearly progression rate in cIMT SDS (β=0.20 [95% CI, 0.13-0.28]) remained positive during the initial 4.5-year follow-up period but slowed down quadratically with increasing observation time (β=-0.02 [95% CI, -0.03 to -0.01]). Risk factors for increased cIMT SDS included time since baseline, younger age, higher height SDS, female sex, elevated diastolic blood pressure, and lower serum albumin, but not estimated glomerular filtration rate. In patients with progressive CKD, higher albuminuria was additionally associated with an increase in cIMT SDS. In patients with stable CKD, serum phosphate and time were the only risk factors identified for elevated cIMT SDS. Annual rates of change in blood pressure were positively correlated with the rate of change in cIMT SDS within the first 4.5 years (for systolic: β=0.42 [95% CI, 0.22-0.62]; for diastolic: β=1.56 [95% CI, 1.01-2.11]).

Conclusions: The results show a significant longitudinal increase in cIMT SDS in children with CKD. Changes in blood pressure are associated with the progression of cIMT SDS, suggesting a relevant impact of blood pressure modulation on cIMT SDS.

Keywords: cardiovascular disease; carotid intima‐media thickness; chronic kidney disease; hypertension; pediatric.

Figure 1. Patient and visit selection (*baseline visit criteria: eGFR<60 mL/min per 1.73 m², age 6–17 years).

cIMT indicates carotid intima‐media thickness; eGFR, estimated glomerular filtration rate; and 4C, Cardiovascular Comorbidity in Children With CKD study.

Figure 2. Average population‐level cIMT SDS prediction for male (A, C, E) and female (B, D, F) patients (baseline age: 11 years), with congenital anomalies of the kidney and urinary tract diagnosis based on median baseline covariate values.

BP indicates blood pressure; cIMT, carotid intima‐media thickness; and SDS, SD score.

Figure 3. Average population‐level cIMT SDS prediction for male (A) and female (B) patients (baseline age: 11 years), with congenital anomalies of the kidney and urinary tract diagnosis and stable chronic kidney disease based on median baseline covariate values.

cIMT indicates carotid intima‐media thickness; and SDS, SD score.

Figure 4. Average population‐level cIMT SDS prediction for male (A, C) and female (B, D) patients (baseline age: 11 years), with congenital anomalies of the kidney and urinary tract diagnosis and progressive chronic kidney disease based on median baseline covariate values.

BP indicates blood pressure; cIMT, carotid intima‐media thickness; and SDS, SD score.

Figure 5. Progression of cIMT SDS depending on BP SDS dynamics over time.

Test for linear relationships between absolute change per year in cIMT SDS (Δ cIMT SDS) with absolute change per year in systolic blood pressure BP SDS (Δ systolic BP SDS) and diastolic blood pressure BP SDS (Δ diastolic BP SDS) within first 4.5 years of follow‐up. BP indicates blood pressure; cIMT, carotid intima‐media thickness; and SDS, SD score.