Homocysteine and Arginine-to-Asymmetric Dimethylarginine Ratio Associated With Blood Pressure Abnormalities in Children With Early Chronic Kidney Disease

Background: Less attention has been paid to evaluating subclinical cardiovascular disease (CVD) in the early stage of pediatric chronic kidney disease (CKD). Ambulatory blood pressure monitoring (ABPM) and arterial stiffness are the earliest detectable assessments of subclinical CVD. Asymmetric dimethylarginine (ADMA) is an analog of L-arginine (ARG) that inhibits nitric oxide (NO) production; thus the ARG-to-ADMA ratio (AAR) is an index of NO. Homocysteine (HCY) is a risk factor for CVD and it can be metabolized to L-cysteine (CYS). Given that HCY and ADMA/NO are closely linked and related to hypertension, we therefore investigated whether ARG and HCY metabolites, arterial stiffness parameters, ABPM profile, and left ventricular hypertrophy (LVH) are interrelated in children and adolescents with early CKD. Methods and Results: This cross-sectional study included 57 pediatric patients with CKD stages 1-3. Two-thirds of the children with CKD stages 1-3 exhibited BP abnormalities accessed by ABPM. Children with CKD stages 2-3 had higher HCY, but lower CYS levels. The plasma HCY level was increased in children with LVH and abnormal ABPM. Systolic BP positively correlated with biomarkers AAR, HCY, and CYS. LV mass positively correlated with AAR, HCY, and CYS. Conclusions: BP abnormalities were prevalent and associated with AAR, HCY, and CYS in children with early CKD. Our data highlighted the effect of NO and the HCY pathway on CKD-related hypertension.