title: Low urinary citrulline/arginine ratio associated with blood pressure abnormalities and arterial stiffness in childhood chronic kidney disease.
abstract: Arginine (ARG) and citrulline (CIT) are essential for nitric oxide (NO) synthesis. Their metabolites are interrelated, and involved in blood pressure (BP) control, chronic kidney disease (CKD), and cardiovascular disease (CVD). Although CVD is the leading cause of mortality in CKD, little is known about subclinical CVD in early-stage childhood CKD. Twenty-four-hour ambulatory BP monitoring and arterial stiffness assessment allows the earlier possible detection of subclinical CVD. We investigated whether urinary CIT and ARG metabolites and their ratios are correlated with BP load and vascular abnormalities in children and adolescents with early-stage CKD. We enrolled 55 pediatric patients with mild-to-moderate CKD. Seventy percent (30/43) had at least one out of BP load abnormality on ambulatory BP monitoring, mainly increased asleep systolic BP (SBP) load (40%), asleep SBP or diastolic BP load > 95th percentile (40%), and nocturnal SBP nondipping (35%). Low urinary CIT level and CIT/ARG ratio were associated with BP load abnormalities in children with early CKD. Urinary CIT/ARG ratio was correlated with arterial stiffness, represented as pulse-wave velocity and augmentation index. SBP and diastolic BP loads were negatively correlated with urinary CIT, ARG, asymmetric dimethylarginine (an endogenous NO synthase inhibitor), and CIT/ARG ratio, while positively associated with dimethylamine/asymmetric dimethylarginine ratio and pulse-wave velocity. Early assessments of BP load abnormalities, urinary biomarkers in the CIT-ARG-NO pathway, and arterial stiffness parameters should increase early preventive care toward decreasing hypertension and CV remodeling in pediatric CKD.
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, Taiwan.
authors.forename: I-Chun
authors.initials: IC
authors.lastname: Lin
authors.affiliation: Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, Taiwan; School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chien-Ning
authors.initials: CN
authors.lastname: Hsu
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, Taiwan.
authors.forename: Mao-Hung
authors.initials: MH
authors.lastname: Lo
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, Taiwan.
authors.forename: Shao-Ju
authors.initials: SJ
authors.lastname: Chien
authors.affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, Taiwan; Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung, Taiwan. Electronic address: tainyl@hotmail.com.
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Tain
mesh_terms: D000293:Adolescent; D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D001794:Blood Pressure / Q000502:physiology; D018660:Blood Pressure Monitoring, Ambulatory; D002648:Child; D002956:Citrulline / Q000378:metabolism / Q000652:urine*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000209:etiology / Q000652:urine*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D063177:Pulse Wave Analysis; D051436:Renal Insufficiency, Chronic / Q000150:complications*; D013624:Taiwan; D066253:Vascular Remodeling; D059289:Vascular Stiffness
chemical_list: D015415:Biomarkers; D002956:Citrulline; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase
keywords: Arginine; chronic kidney disease; hypertension; nitric oxide