Adiposity, Sex, and Cardiovascular Disease Risk in Children With CKD: A Longitudinal Study of Youth Enrolled in the Chronic Kidney Disease in Children (CKiD) Study

Abstract

Rationale & objective: Traditional and nontraditional cardiovascular disease risk factors are highly prevalent in children with chronic kidney disease (CKD). We examined the longitudinal association of adiposity with cardiac damage among children with CKD and explored whether this association was modified by sex.

Study design: Prospective cohort study.

Setting & participants: Children with mild-to-moderate CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study at 49 pediatric nephrology centers across North America.

Exposure: Age- and sex-specific body mass index (BMI) z score.

Outcome: Age- and sex-specific left ventricular mass index (LVMI) z score and left ventricular hypertrophy (LVH).

Analytical approach: Longitudinal analyses using mixed-effects models to estimate sex-specific associations of BMI z scores with LVMI z score and with LVH, accounting for repeated measurements over time.

Results: Among 725 children with 2,829 person-years of follow-up, median age was 11.0 years and median estimated glomerular filtration rate was 52.6mL/min/1.73m2. Nearly one-third of both boys and girls were overweight or obese, median LVMI z score was 0.18 (IQR: -0.67, 1.08), and 11% had LVH. Greater BMI z scores were independently associated with greater LVMI z scores and greater odds of LVH. For each 1-unit higher BMI z score, LVMI z score was 0.24 (95% CI, 0.17-0.31) higher in boys and 0.38 (95% CI, 0.29-0.47) higher in girls (Pinteraction = 0.01). For each 1-unit higher BMI z score, the odds of LVH was 1.5-fold (95% CI, 1.1-2.1) higher in boys and 3.1-fold (95% CI, 1.8-4.4) higher in girls (Pinteraction = 0.005).

Limitations: Not all children had repeated measurements. LVH is a surrogate and not a hard cardiac outcome. The observational design limits causal inference.

Conclusions: In children, adiposity is independently associated with the markers of cardiac damage, LVMI z score and LVH. This association is stronger among girls than boys. Pediatric overweight and obesity may therefore have a substantial impact on cardiovascular risk among children with CKD.

Keywords: Cardiovascular disease (CVD); adiposity; adolescents; body mass index (BMI); cardiac target organ damage; children; chronic kidney disease (CKD); hypertension; left ventricular hypertrophy (LVH); left ventricular mass index (LVMI); obesity; overweight; pediatrics; sex differences; youth.

Conflict of interest statement

Financial Disclosure: The authors declare that they have no relevant financial interests.

Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Scatter plot of age-sex specific Left Ventricular Mass Index (LVMI) z-score and age-sex specific BMI z-score at 1483 visits contributed by 725 participants of the Chronic Kidney Disease in Children (CKiD) study. The average BMI z-score of the current visit and previous visit are shown. Regression lines are shown for males and females and were obtained from a linear mixed model with LVMI z-score as the dependent variable and male sex, BMI z-score, and male sex x BMI z-score interaction term as the independent variables.

Figure 2.

Prevalence of LVH by sex and category of Body Mass Index at 1483 visits contributed by 725 participants of the Chronic Kidney Disease in Children (CKiD) study. LVH was defined as LVMI ≥ age-sex specific 95th percentile. The average BMI of the current visit and previous visit were used.