Serum Renalase Levels in Adolescents with Primary Hypertension

Pediatric Cardiology https://doi.org/10.1007/s00246-018-1891-y ORIGINAL ARTICLE Serum Renalase Levels in Adolescents with Primary Hypertension Marta Lemiesz1 · Edyta Tenderenda‑Banasiuk1 · Dorota Sosnowska2 · Katarzyna Taranta‑Janusz1 · Anna Wasilewska1 Received: 29 November 2017 / Accepted: 2 May 2018 © The Author(s) 2018 Abstract The prevalence of hypertension in pediatric populations continues to rise. Recent studies suggest that renalase plays an important role in blood pressure regulation. The aim of this study was to evaluate serum renalase concentrations in hypertensive children. This study was a prospective cohort analysis of 88 adolescents (40 girls; 48 boys) aged 11–18 years, divided into two groups: HT—38 subjects with primary hypertension; and R (reference group)—50 subjects with normal blood pressure. Serum renalase concentration was measured using a commercial enzyme-linked immunosorbent assay kit. Hypertensive patients had higher serum renalase levels (median 29.8 µg/mL; Q1–Q3: 26.1–35.8) than the reference group (median 26.8; Q1–Q3: 22.96–29.4, p < 0.01). Serum renalase was strongly related to serum uric acid levels. In hypertensive patients, serum renalase was positively correlated with 24-h systolic blood pressure (SBP) and 24-h diastolic blood pressure (DBP) and with 24-h SBP and 24-h DBP Z-score (LMS). Our results allow us to conclude that serum renalase correlates with blood pressure elevation. Special attention should be drawn to the correlation between renalase and serum uric acid levels not only in hypertensive, but also in normotensive teenagers. Further studies are needed to answer the question of whether increased serum renalase may be a predisposing factor to hypertension in normotensive patients with hyperuricemia. Keywords Blood pressure · Children · Renalase · Uric acid Abbreviations ABPM Ambulatory blood pressure monitoring AT1 Angiotensin receptor BMI Body mass index BP Blood pressure CA Catecholamine DBP Diastolic blood pressure DBPL Diastolic blood pressure load eGFR Estimated glomerular filtration rate HT Hypertension R Reference group RAS Renin–angiotensin system RIA Radioimmunoassay SBP Systolic blood pressure * Marta Lemiesz 1 Department of Pediatrics and Nephrology, Medical University of Bialystok, 17 Waszyngton Street, 15‑274 Białystok, Poland 2 Department of Obstetrics ‑ Gynecology, Medical Hospital in Garwolin, Garwolin, Poland SBPL Systolic blood pressure load UAER Urinary albumin excretion rate Background While the burden of hypertension in adults is widely known, it is becoming a growing problem among children and teens. Current estimates describe up to 5% of children as hypertensive [1], and the American Heart Association reports that up to 15% of adolescents have abnormal blood pressure (BP), defined as > 120/80 mmHg [2]. In recent years, renalase, a new flavoprotein, has been shown to be involved in the regulation of blood pressure and cardiovascular function [3]. Renalase is strongly expressed in the kidney, but is also present in the heart, skeletal muscle, liver, adrenals, endothelium, peripheral nerves, central nervous system, and also human adipose tissue [4]. In the kidney, it is mainly produced in the proximal tubule, but it is also found in the glomerulus and distal tubule. The kidney produces the majority of the circulating form, and a very high concentration of the renalase is found in the urine. Circulating prorenalase is quickly activated by high catecholamine levels or by an 13 Vol.:(0123456789) Pediatric Cardiology increase in blood pressure [5, 6]. It is known that renalase metabolizes dopamine most efficiently, followed by epinephrine, and then norepinephrine. Additionally, it has been shown that renalase may have a significant hemodynamic effect in vivo; for example, it may decrease cardiac contractility and heart rate [6]. Results of experimental studies strongly suggest that renalase deficiency might be related to excess dopamine, epinephrine, and norepinephrine states, and accordingly to elevated blood pressure and hypertension; however, recent clinical studies have not confirmed this observation [7]. These conflicting results signal a need for further investigation. To the best of our knowledge, only a few studies on renalase in pediatric hypertensive populations have been published thus far. The aim of our study was to examine serum renalase concentration in adolescents with primary hypertension and whether it correlates with blood pressure and serum uric acid. Methods The current prospective cohort study was approved by the ethics committee of the Medical University of Białystok, Poland, in accordance with the Declaration of Helsinki. Informed consent was obtained from parents or guardians of all participants and from children older than 16 years. The study included 38 hypertensive adolescents (11 female and 27 male) aged 11–18 years, who were referred to our unit (Department of Pediatrics and Nephrology, Medical University of Białystok, Poland) for further diagnostics between June 2012 and December 2013. The reference group (R) consisted of 50 age-matched normotensive, healthy teenagers. Clinical histories and blood samples were collected at the study site. Identification of Patients Patients who met all the following inclusion criteria were enrolled in the study: (1) age 11–18 years; (2) primary arterial hypertension, defined as systolic (SBP) and/or diastolic blood pressure (DBP) ≥ 95th percentile, measured on three or more occasions [1]; (3) no clinical or laboratory signs of infection; (4) normal levels of cortisol, thyroid-stimulating hormone (TSH), and renal function; (5) lack of proteinuria; (6) lack of antibiotic within the prior 4 weeks; and (7) signed informed consent. Patients with a history of heart failure, renal or hepatic dysfunction, diabetes mellitus, systemic inflammatory conditions, autoimmune diseases, clinical or laboratory signs of secondary hypertension (documented thyroid, kidney, or heart disease, abnormal Doppler of the renal arteries), oral contraceptive use, current hypertensive 13 therapy, or on medications known to affect serum uric acid levels and blood pressure values were excluded from the study. Identification of the Reference Group The inclusion criteria for the reference group were as follows: (1) female and male patients aged 11–18 years who were attending the general pediatric nephrology outpatient clinic at the Department of Pediatrics and Nephrology, Medical University of Bialystok, Poland; (2) signed informed consent. Health status was determined by the subjects’ medical history and routine laboratory examinations were performed to rule out the presence of acute or chronic disease. For each subject, a careful clinical history and physical examination were performed. Body weight and height were measured using a balance beam scale and a pediatric wall-mounted stadiometer, and body mass index (BMI) was calculated. Age- and h (...truncated)