Could arterial stiffness be early reversible target organ damage test in childhood hypertension?

OBJECTIVE: The recommended treatment for hypertension (HTN) in children has been revised recently. This study aimed to present the changes in target organ damage (TOD) and arterial stiffness parameters after treatment in children with primary HTN who were managed in accordance with the 2016 European Society of Hypertension Guidelines. METHODS: Patients with primary HTN included in this study were newly diagnosed, untreated, and were followed-up for a minimum of 6 months. HTN was confirmed by 24-h ambulatory blood pressure monitoring (ABPM). All patients underwent the following assessments: anthropometrical measurements of body mass index (BMI), carotid intima-media thickness (cIMT), left ventricular mass index (LVMI), plasma creatinine, urea, electrolytes, uric acid, fasting plasma glucose, blood lipids, urinalysis, urine culture, and first morning urine albumin tocreatinine ratio. The ABPM device performed measurements such as central blood pressure (cBP) and pulse wave velocity (PWV). RESULTS: Thirty-two of 104 patients were enrolled. Seventeen patients were male, and 53% were obese. Compared with pretreatment, creatinine, urea, systolic BP (SBP), diastolic BP (DBP), systolic load, diastolic load, central SBP (cSBP), cSBP z score, cDBP, and PWV z score decreased, whereas LVMI and BMI z scores were unchanged. CONCLUSION: After BP improvement, while LVMI did not regress, the cSBP, cSBP z, and PWV z score values, which are markers of arterial stiffness, regressed. This supports the corrective effect of BP control on the cardiovascular system even in a short-term follow-up. Further longitudinal studies are needed for the assessment of BP control on arterial stiffness in childhood.

Evaluation of neuropsychological development of children diagnosed with primary monosymptomatic nocturnal enuresis: A pilot study.

OBJECTIVE: Studies on primary monosymptomatic nocturnal enuresis have supported neuromotor development delay. This study aims to examine the neuropsychological development of children with primary monosymptomatic nocturnal enuresis. MATERIAL AND METHODS: This study included 30 children diagnosed with primary monosymptomatic nocturnal enuresis and 30 healthy children. Both groups were analyzed by pediatric psychologists using the Wechsler Intelligence Scale for Children-Revised (WISC-R) and the Bender Gestalt Visual Motor Detection test. The WISC-R test is an intelligence test that includes six verbal subscales (information, similarities, arithmetic, vocabulary, judgment, and digit span) and six performance subscales (picture completion, picture arrangement, block design, object assembly, coding, and labyrinths). The Bender Gestalt test is a psychological assessment instrument used to evaluate visuomotor functioning, visuospatial functions, spatial memory, visuomotor integration skills, and visual perception skills. RESULTS: There were no differences in age (7.66±0.9 versus 8±1.07 years, p>0.05) or sex (20 females versus 20 males, p>0.05) between the groups. Picture completion (p=0.024), picture arrangement (p=0.001), and object assembly test (p=0.000) performance was found to be worse in subjects with primary monosymptomatic nocturnal enuresis. Similarity (p=0.021) and judgment tests (p=0.048) of the verbal subtests were also found to be delayed in the nocturnal enuresis cases. CONCLUSION: Our results suggest that children with nocturnal enuresis have lower performance compared with the control group in terms of abstract thinking, correct expression of thought, cause-result relation, short-term memory, and problem-solving ability. These children should be routinely tested by neurodevelopment tests and receive support in areas in which they are delayed.

The Clinical and Mutational Spectrum of Turkish Patients with Cystinosis.

BACKGROUND AND OBJECTIVES: Infantile nephropathic cystinosis is a severe disease that occurs due to mutations in the cystinosis gene, and it is characterized by progressive dysfunction of multiple organs; >100 cystinosis gene mutations have been identified in multiple populations. Our study aimed to identify the clinical characteristics and spectrum of cystinosis gene mutations in Turkish pediatric patients with cystinosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We identified the clinical characteristics and spectrum of cystinosis gene mutations in Turkish patients with cystinosis in a multicenter registry that was established for data collection. The data were extracted from this registry and analyzed. RESULTS: In total, 136 patients (75 men and 61 women) were enrolled in the study. The most common clinical findings were growth retardation, polyuria, and loss of appetite. None of the patients had the 57-kb deletion, but seven novel mutations were identified. The most common mutations identified were c.681G>A (p.Glu227Glu; 31%), c.1015G>A (p.Gly339Arg; 22%), and c.18_21 del (p.Thr7Phefs*7; 14%). These mutations were associated with earlier age of disease onset than the other mutations. To understand the effects of these allelic variants on clinical progression, the mutations were categorized into two major groups (missense versus deletion/duplication/splice site). Although patients with missense mutations had a better eGFR at the last follow-up visit, the difference was not significant. Patients in whom treatment began at age <2 years old had later onset of ESRD (P=0.02). Time to ESRD did not differ between the patients with group 1 and group 2 mutations. CONCLUSIONS: The most common cystinosis gene mutations identified in Turkey were c.681G>A (p.Glu227Glu), c.1015G>A (p.Gly339Arg), and c.18_21 del (p.Thr7Phefs*7). Patients with less severe cystinosis gene mutations tend to have better kidney outcome.

The Association between Serum 25-Hydroxy Vitamin D Level and Urine Cathelicidin in Children with a Urinary Tract Infection.

OBJECTIVE: Cathelicidin is an important antimicrobial peptide in the urinary tract. Cathelicidin expression is strongly stimulated by 1,25-dihydroxy vitamin D in epithelial cells, macrophages/monocytes, and neutrophils. Vitamin D and cathelicidin status in children with urinary tract infection (UTI) caused by Escherichia coli is unknown. To establish the relationship between serum vitamin D and urine cathelicidin levels in children with a UTI caused by Escherichia coli. METHODS: Serum 25-hydroxy vitamin D and urine cathelicidin levels were measured in 36 patients with UTI (mean age 6.8±3.6 years, range: 0.25-12.6 years) and 38 controls (mean age 6.3±2.8 years, range: 0.42-13 years). RESULTS: There were no significant differences in urine cathelicidin levels between the study and control groups (p>0.05). Eight (22.2%) patients in the study group and 21 (58.3%) children in the control group were found to have sufficient vitamin D (≥20 ng/mL). Patients with sufficient vitamin D had higher urine cathelicidin levels than the controls with sufficient vitamin D (respectively 262.5±41.1 vs. 168±31.6 ng/mL, p=0.001). There were no significant differences between the patients and controls with insufficient vitamin D (p>0.05). CONCLUSION: The children with vitamin D insufficiency may not be able to increase their urine cathelicidin level during UTI caused by Escherichia coli. There is a need of prospective studies in order to prove a beneficial effect of vitamin D supplementation for the restoration of cathelicidin stimulation and consequently for prevention of UTI recurrence.

Urinary Netrin-1: A New Biomarker for the Early Diagnosis of Renal Damage in Obese Children.

OBJECTIVE: Urinary netrin-1 is a new marker to demonstrate early tubular damage. The aim of this study was to determine whether urinary netrin-1 is increased in obese children. METHODS: A total of 68 normoalbuminuric and normotensive obese patients and 65 controls were included in the study. Urine samples were collected for assessment of urinary phosphorus, sodium, potassium, creatinine, albumin, and netrin-1. Blood samples were collected for measurements of fasting glucose, insulin, lipid, phosphorus, sodium, potassium, and creatinine levels. Homeostatic model assessment insulin resistance index was calculated. RESULTS: Gender and age were similar between obese and control groups (12.01±3.03 vs. 11.7±3.2 years, p=0.568 and 33 vs. 35 girls, p=0.543, respectively). Obese patients had significantly higher netrin-1 excretion than the controls (841.68±673.17 vs. 228.94±137.25 pg/mg creatinine, p=0.000). Urinary netrin-1 level was significantly higher in obese subjects with insulin resistance compared to those without insulin resistance (1142±1181 vs. 604.9±589.91 pg/mg creatinine, p=0.001). CONCLUSION: In normotensive and normoalbuminuric obese children, urinary netrin-1 level can increase before onset of albuminuria. Urinary netrin-1 excretion appears to be affected predominantly by insulin resistance and hyperinsulinemia. Urinary netrin-1 may be a new biomarker for determining early tubular injury in obese children.

Elevated Urinary T Helper 1 Chemokine Levels in Newly Diagnosed Hypertensive Obese Children.

OBJECTIVE: Increasing evidence suggests that T helper (Th) cells play a significant role in the pathogenesis of hypertension. The aim of this study was to evaluate the effect of obesity and anti-hypertensive treatment on urinary Th1 chemokines. METHODS: The study groups consisted of three types of patients: hypertensive obese, healthy, and non-hypertensive obese. Pre-treatment and post-treatment samples of the hypertensive obese group and one sample from the other two groups were evaluated for urinary chemokine: regulated on activation, normal T cell expressed and secreted (RANTES), interferon-gamma-inducible protein 10 (IP10), and monokine induced by interferon-gamma (MIG). In the hypertensive obese group, urine microalbumin: creatinine ratio was examined before and after treatment. We recommended lifestyle changes to all patients. Captopril was started in those who could not be controlled with lifestyle changes and those who had stage 2 hypertension. RESULTS: Twenty-four hypertensive obese (mean age 13.1), 27 healthy (mean age 11.2) and 22 non-hypertensive obese (mean age 11.5) children were investigated. The pre-treatment urine albumin: creatinine ratio was positively correlated with pre-treatment MIG levels (r=0.41, p<0.05). RANTES was significantly higher in the pre-treatment hypertensive and non-hypertensive obese group than in the controls. The urinary IP10 and MIG levels were higher in the pre-treatment hypertensive obese group than in the non-hypertensive obese. Comparison of the pre- and post-treatment values indicated significant decreases in RANTES, IP10, and MIG levels in the hypertensive obese group (p<0.05). CONCLUSION: Th1 cells could be activated in obese hypertensive children before the onset of clinical indicators of target organ damage. Urinary RANTES seemed to be affected by both hypertension and obesity, and urinary IP10 and MIG seemed to be affected predominantly by hypertension.