Haptoglobin is associated with nocturnal blood pressure non-dipping in children with chronic kidney disease

Abstract

Blood pressure (BP) follows a circadian rhythm that depends partly on endothelial nitric oxide (NO) bioavailability. Cell-free hemoglobin rapidly scavenges NO, and haptoglobin functions as a capacity-limited plasma buffer facilitating hemoglobin clearance. Whether reduced circulating haptoglobin contributes to circadian rhythm–related vascular dysregulation in pediatric chronic kidney disease (CKD) remains unclear. Sixty children with CKD were enrolled, and plasma haptoglobin levels were measured by enzyme-linked immunosorbent assay. Twenty-five participants underwent 24-hour ambulatory BP monitoring. Nocturnal systolic BP non-dipping was defined as <10% decline in nighttime values. Multivariable Firth penalized logistic regression adjusted for age and sex. Restricted cubic spline modeling assessed dose–response patterns. Fifteen of 25 children (60%) exhibited nocturnal non-dipping. Plasma haptoglobin levels were significantly lower in non-dippers than in dippers. Each 10 mg/dL increase in haptoglobin was independently associated with lower odds of non-dipping (adjusted OR 0.74, 95% CI 0.49–0.99; p  = 0.044). Spline modeling suggested a threshold-like increase in risk at lower concentrations. Lower circulating haptoglobin is independently associated with nocturnal BP non-dipping in children with CKD. These findings suggest that reduced hemoglobin-buffering capacity may contribute to impaired circadian BP regulation, although mechanistic confirmation is required.