The Association between Nitric Oxide Pathway, Blood Pressure Abnormalities, and Cardiovascular Risk Profile in Pediatric Chronic Kidney Disease

Abstract

Cardiovascular disease (CVD) is common in chronic kidney disease (CKD), while major CV events are rare in young CKD patients. In addition to nitric oxide (NO)-related biomarkers, several surrogate markers have been assessed to stratify CV risk in youth with CKD, including 24-h ambulatory blood pressure monitoring (ABPM), carotid artery intima-media thickness (cIMT), pulse wave velocity (PWV), ABPM-derived arterial stiffness index (AASI), flow-mediated dilatation (FMD), and left ventricular mass index (LVMI). The aim of this study was to identify subclinical CVD through the analysis of indices of CV risk in children and adolescents with CKD. Between 2016 and 2018, the prospective observational study enrolled 125 patients aged 3 to 18 years with G1–G4 CKD stages. Close to two-thirds of young patients with CKD exhibited blood pressure (BP) abnormalities on ABPM. CKD children with abnormal office BP showed lower plasma arginine levels and arginine-to-asymmetric dimethylarginine (ADMA) ratio, but higher ratios of ADMA-to-symmetric dimethylarginine (SDMA) and citrulline-to-arginine. High PWV and AASI, indices of arterial stiffness, both strongly correlated with high BP load. Additionally, LV mass and LVMI exhibited strong correlations with high BP load. Using an adjusted regression model, we observed the citrulline-to-arginine ratio was associated with 24-h systolic and diastolic BP, systolic blood pressure (SBP) load, and diastolic blood pressure (DBP) load. Early assessments of NO-related parameters, BP load abnormalities, arterial stiffness indices, and LV mass will aid in early preventative care toward decreasing CV risk later in life for children and adolescents with CKD.

Association of Trimethylamine, Trimethylamine N-oxide, and Dimethylamine with Cardiovascular Risk in Children with Chronic Kidney Disease

“…Of note is that up to 48% of children with CKD stage G1 had BP abnormalities on ABPM. Our findings are consistent with previous reports wherein hypertension is extremely prevalent in CKD children, even in an early stage [20][21][22][23]. The present study supported the notion that ABPM is superior to office BP in identifying children with BP abnormalities [24].…”

“…AASI, an index of arterial stiffness, has been proposed as a surrogate marker to predict CV morbidity and mortality [18]. Our previous report demonstrated that high AASI is related to BP abnormalities in CKD children, even in an early stage [23]. The present results showed AASI was higher in children with CKD stage G2-G4 than those with stage G1, which ties well with the previous study in that high AASI worsens GFR decline in adult CKD patients [25].…”

Association between Acrylamide Metabolites and Cardiovascular Risk in Children With Early Stages of Chronic Kidney Disease

“…In keeping with previous studies, certain markers of CV risk tend to present in children with CKD, even in an early stage, such as ABPM abnormalities [4,6,7,16], uric acid [17], and AASI [18]. In the current study, up to 47.9% of children with CKD stage G1 displayed abnormal ABPM profiles.…”

“…Hypertension is the most important risk factor for premature CVD [5]. More than 50% of children with early stages of CKD exhibited blood pressure (BP) abnormalities on 24 h ambulatory BP monitoring (ABPM) [6,7]. Additionally, several surrogate markers have been applied to stratify the cardiovascular risk in CKD children, including left ventricular (LV) mass, LV mass index (LVMI), and ambulatory arterial stiffness index (AASI) [8].…”

“…However, study of the effect of acrylamide exposure on hypertension and CVD is limited, especially in pediatric population. Our previous report demonstrated that in CKD children, abnormal BP was associated with an impaired nitric oxide (NO) pathway [6]. The interplay between NO and oxidative stress has been linked to hypertension and CKD [12,13], whereas whether acrylamide exposure affects the NO pathway and relates to the CV risk in CKD children is largely unknown.…”