Sex-specific associations of HDL cholesterol with atherosclerosis in pediatric chronic kidney disease

Introduction: Children and adolescents with chronic kidney disease (CKD) and kidney transplantation have a high burden of cardiovascular morbidity and premature mortality, with excess mortality particularly pronounced in girls and young women. Dyslipidemia is common in pediatric CKD, and high-density lipoprotein (HDL) cholesterol may be qualitatively altered, but it is unclear whether the lipid profiles affect the vasculature differently in girls and boys.
Methods: We analyzed longitudinal data from 691 children and adolescents with CKD stages 3–5, on dialysis, and/or after kidney transplantation enrolled in the 4C Study. Lipids (total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, triglycerides) and carotid intima-media thickness (IMT) were assessed. Multivariable adjusted linear mixed-effects models, stratified by treatment modality, were used to examine the effect of sex on lipid levels and to assess sex-specific associations between lipid parameters and IMT.
Results: Girls had consistently higher HDL and, to a lesser extent, higher total cholesterol levels than boys across CKD, dialysis, and transplantation. Among all lipid parameters, only HDL cholesterol showed a significant sex interaction with IMT. Higher HDL cholesterol was associated with greater IMT in girls with CKD and after kidney transplantation, whereas no such association was observed in boys. No sex-specific interactions with IMT were detected for total cholesterol, low-density lipoprotein cholesterol, or triglycerides (Figure).

Conclusion: Biological sex modifies the association between HDL cholesterol and carotid IMT in pediatric patients with CKD and kidney transplantation. Higher HDL cholesterol levels do not uniformly indicate a favorable vascular profile in girls and may contribute to their increased cardiovascular vulnerability.