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.
Highlights
Non-communicable diseases (NCDs) present the greatest public health challenges of the 21st century and account for two-thirds of all global deaths [1]
Our major findings are as follows: (1) approximately two-thirds of children and adolescents with chronic kidney disease (CKD) stage G1–G4 had blood pressure (BP) abnormalities on ambulatory blood pressure monitoring (ABPM); (2) plasma arginine level and arginine-to-asymmetric dimethylarginine (ADMA) ratio were lower, whereas ADMA-to-symmetric dimethylarginine (SDMA) and citrulline-to-arginine ratios were higher in CKD children with abnormal office BP; (3) pulse wave velocity (PWV) and LV mass were increased in the case of CKD stage G2–G4 compared to those with stage G1; (4) PWV and left ventricular mass index (LVMI) was higher in CKD children with abnormal vs. normal ABPM profile; (5) PWV, LV mass, and LVMI exhibited stronger correlations with elevated BP load than other cardiovascular surrogate markers; and (6) the citrulline-to-arginine ratio was associated with 24-h systolic blood pressure (SBP), 24-h diastolic BP (DBP), SBP load, and DBP load in the adjusted regression model
As arginine is the substrate for nitric oxide synthase (NOS) and arginine-to-ADMA ratio is referred to as an index of nitric oxide (NO) bioavailability [29], our results suggest NO deficiency is related to the development of hypertension in children and adolescents with early-stage CKD
Summary
Non-communicable diseases (NCDs) present the greatest public health challenges of the 21st century and account for two-thirds of all global deaths [1]. Cardiovascular disease (CVD) alone makes up approximately 50% of all NCD deaths. Major CV events tend to occur in adults and are rare in children. The stiffening of the arteries can begin in early life. Subclinical CVD presenting in children is not detectable by conventional methods [2]. Children with chronic kidney disease (CKD) are at high risk of developing CVD [3]. By the time CKD children require dialysis or kidney transplantation, their CV mortality is 30-fold higher than the general population [4], indicating the need for early identification and prevention
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
