High citrulline-to-arginine ratio associated with blood pressure abnormalities in children with early chronic kidney disease

Background: Nitric oxide (NO) is involved in hypertension and chronic kidney disease (CKD). NO synthase can metabolize l-arginine (ARG) to generate NO and l-citrulline (CIT). Two methylated ARG derivatives, asymmetric and symmetric dimethylarginine, are also involved in NO deficiency. Thus it was hypothesized that their combined ratios relate to blood pressure (BP) abnormalities in children with early CKD. Methods and Results: The relationship between these ARG metabolites in plasma was examined using 24-h ambulatory BP monitoring (ABPM) profile in children and adolescents with CKD stages 1-3 (n=44). Approximately 20.4% (9/44) of children with CKD stages 1-3 were diagnosed with hypertension on clinical BP measurement, and 77.3% (33/44) had BP abnormalities on ABPM, including increased BP load, nocturnal BP non-dipping, and nocturnal hypertension. Children with CKD stages 2-3 were more prevalent with abnormal BP on ABPM, and had a higher level of CIT and CIT-to-ARG ratio than those with stage 1. Furthermore, high CIT-to-ARG ratio was significantly correlated with abnormal ABPM profile, including nocturnal hypertension, increased diastolic BP load, and nocturnal BP non-dipping. Higher CIT level was significantly correlated with increased diastolic BP load and overall ABPM profile. Conclusions: Plasma CIT-to-ARG ratio may serve as a useful marker of cardiovascular outcome in children with early CKD.