The First Pediatric Case of an IFT140 Heterozygous Deletion Causing Autosomal Dominant Polycystic Kidney Disease: Case Report.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease, which is mainly caused by pathogenic variants in two particular genes: PKD1 and PKD2. ADPKD caused by variants in other genes (GANAB or IFT140) is very rare. Case Report: In a 6-year-old girl examined for abdominal pain, a cystic mass in the upper part of the right kidney was detected during an abdominal ultrasound. She was referred to pediatric oncology and urology for suspicion of a tumorous mass and the condition was assessed as a cystic nephroma. A heminephrectomy was then performed on the upper cystic part of the right kidney. The histological examination was inconclusive; therefore, genetic testing was recommended. Kidney and liver cysts were detected sonographically in the mother, but DNA analysis of the PKD1 and PKD2 genes did not reveal any pathogenic variant; the cause of the pathological formation in the kidneys remained unclear. Nine years later, next-generation sequencing of a panel of genes for kidney disease was performed and a heterozygous deletion was found on chromosome 16; this included exon 13 of the IFT140 gene. The same deletion was found in the patient's mother. Currently, the patient is 14 years old and has mild sonographic findings, normal glomerular filtration, mild proteinuria, and hypertension. Conclusion: Pathogenic variants of the IFT140 gene very rarely cause ADPKD; however, they should be considered in all children with autosomal dominant forms of PKD and asymmetric/atypical cystic kidney involvement or negative findings of PKD1 and PKD2.

Kidney volume normative values in Central European children aged 0-19 years: a multicenter study.

BACKGROUND AND OBJECITVES: The currently available kidney volume normative values in children are restricted to small populations from single-centre studies not assessing kidney function and including none or only a small number of adolescents. This study aimed to obtain ultrasound-based kidney volume normative values derived from a large European White/Caucasian paediatric population with normal kidney function. METHODS: After recruitment of 1427 children aged 0-19 years, 1396 individuals with no history of kidney disease and normal estimated glomerular filtration rate were selected for the sonographic evaluation of kidney volume. Kidney volume was correlated with age, height, weight, body surface area and body mass index. Kidney volume curves and tables related to anthropometric parameters were generated using the LMS method. Kidney volume predictors were evaluated using multivariate regression analysis with collinearity checks. RESULTS: No clinically significant differences in kidney volume in relation to height were found between males and females, between supine and prone position and between left and right kidneys. Males had, however, larger age-related kidney volumes than females in most age categories. For the prediction of kidney volume, the highest coefficient correlation was observed for body surface area (r = 0.94), followed by weight (r = 0.92), height (r = 0.91), age (r = 0.91), and body mass index (r = 0.67; p < 0.001 for all). CONCLUSIONS: This study presents LMS-percentile curves and tables for kidney volume which can be used as reference values for children aged 0-19 years.

Masked Hypertension in Healthy Children and Adolescents: Who Should Be Screened?

PURPOSE OF REVIEW: The goal is to review masked hypertension (MH) as a relatively new phenomenon when patients have normal office BP but elevated out-of-office BP. Firstly, it was described in children in 2004. It has received increased attention in the past decade. RECENT FINDINGS: The prevalence of MH in different pediatric populations differs widely between 0 and 60% based on the population studied, definition of MH, or method of out-of-office BP measurement. The highest prevalence of MH has been demonstrated in children with chronic kidney disease (CKD), obesity, diabetes, and after heart transplantation. In healthy children but with risk factors for hypertension such as prematurity, overweight/obesity, diabetes, chronic kidney disease, or positive family history of hypertension, the prevalence of MH is 9%. In healthy children without risk factors for hypertension, the prevalence of MH is very low ranging 0-3%. In healthy children, only patients with the following clinical conditions should be screened for MH: high-normal/elevated office BP, positive family history of hypertension, and those referred for suspected hypertension who have normal office BP in the secondary/tertiary center.

Early Vascular Aging in Children With Type 1 Diabetes and Ambulatory Normotension.

Background: Preliminary data suggest that target organ damage (TOD) and early vascular aging (EVA) may occur in children with normal blood pressure (BP). Objectives: To analyze TOD and EVA in normotensive (BP <95th percentile on ambulatory BP monitoring) type 1 diabetes children (T1D) in comparison to healthy controls (C). Subjects: 25 T1D aged 13.9 ± 2.6 years and 22 C aged 14.0 ± 3.4 years. Methods: We analyzed age- and height-related pulse wave velocity (PWV) Z-scores and expected PWV based on age, height, and mean arterial pressure (MAP). Expected vascular age based on measured PWV was calculated from pooled pediatric and adult PWV norms. Left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), and urinary albumin/creatinine ratio (ACR) were obtained as markers of TOD. Results: T1D and C groups did not differ in anthropometry, ambulatory, LVMI, and ACR. However, median age- and height-related PWV Z-scores were higher in T1D compared to C (1.08 vs. 0.57, p = 0.006; 0.78 vs. 0.36, p = 0.02, respectively). Mean (±SD) difference between measured and expected PWV was 0.58 ± 0.57 in T1D vs. 0.22 ± 0.59 in C, p = 0.02. The mean (±SD) difference between chronological and expected vascular age was 7.53 ± 7.74 years in T1D vs. 2.78 ± 7.01 years in C, p = 0.04. Conclusion: Increased arterial stiffness and increased intraindividual differences between expected and measured PWV as well as between chronological and expected vascular age indicate that EVA may develop in T1D children even at normal ambulatory BP levels.

Effect of the DASH-diet and salt Kardisal® on blood pressure in adolescents with prehypertension (Cooperative multicentre interventional study).

BACKGROUND: In a cooperative multi-center interventional study of 60 probands with prehypertension and normal BMIs were followed for 3 months. DESIGN: The intervention included the DASH diet for 3 months in 30 probands plus sodium limited intake using the low sodium salt Kardisal® (60% NaCl, 40% KCl) (group A) and the DASH diet for 3 months in 30 probands without Kardisal® (group B). RESULTS: In group A (n=26 probands evaluated) the systolic blood pressure (median) decreased significantly from 138 to 129 mmHg (p<0.001), while the diastolic blood pressure had a statistically non-significant decrease. In group B (n=25 probands evaluated) the SBP decreased significantly from 135 to 132 mmHg (p<0.001), and the DBP decreased significantly from 85 to 69 mmHg (p<0.001). CONCLUSION: Despite a relatively short period on the DASH diet, the intervention produced a significant decrease in the blood pressure of prehypertensive adolescents. The additional use of a low sodium salt for home cooking was not found to have any advantages over the DASH diet alone.

Can auscultatory blood pressure normative values be used for evaluation of oscillometric blood pressure in children?

The aim of the study was to analyze whether auscultatory normative values (Fourth Task Force [4TF]) can be applied to blood pressure (BP) obtained by oscillometric devices. The authors performed a retrospective analysis of oscillometric office BP and ambulatory BP monitoring in 229 children (116 boys), median age 15.31 years. Office systolic BP (SBP) and diastolic BP (DBP) values were converted into Z scores using 4TF and oscillometric (German Health Interview and Examination Survey for Children and Adolescent [KiGGS]) reference values. There was good correlation between the two normative methods (r=0.9773 for SBP, r=0.9627 for DBP). Results from Bland-Altman test revealed only minimal differences in Z scores between 4TF and KiGGS for SBP, but a significant proportional error for DBP. 4TF and KiGGS Z scores were equally predictive of ambulatory hypertension. In conclusion, auscultatory and oscillometric normative data are interchangeable for SBP but not for DBP.

HbA1c but not diabetes duration predicts increased arterial stiffness in adolescents with poorly controlled type 1 diabetes.

BACKGROUND: The prevalence of macrovascular complications is probably underestimated in children with type 1 diabetes (T1D). Arterial stiffness (AS) is a subclinical marker of cardiovascular (CV) risk. The most validated, non-invasive method for AS measurement is pulse wave velocity (PWV). Only a few PWV studies have been performed in children with T1D. OBJECTIVE: To explore the risk factors associated with AS in adolescents with suboptimally controlled T1D. PATIENTS AND METHODS: Seventy-seven adolescents with T1D were included (39 girls, 38 boys) in this study. The adolescents had a median age of 16 yr (IQR 14-17), median duration of T1D was 9 yr (IQR 6-16), and HbA1c 71 mmol/mol (median, IQR 62-81). PWV was measured as the carotid-femoral pulse transmission time and converted into standard deviation scores (SDS) (adjusted for gender and age) using normative values for children. The risk factors assessed were HbA1c, T1D duration, treatment modality, serum lipids, and blood pressure (BP) measured via ambulatory blood pressure monitoring (ABPM). RESULTS: The PWV did not differ from the reference data (median PWV was 5.1 m/s, i.e., -0.01 SDS). A significant positive association was observed between PWV-SDS and HbA1c (p = 0.001), total cholesterol (p = 0.003), LDL-cholesterol (p = 0.003), but not T1D duration (p = 0.78) according to the univariate analyses. In the multivariate model, the only significant variable that remained positively associated with PWV-SDS was HbA1c (p = 0.03). CONCLUSIONS: Most adolescents with suboptimally controlled T1D have normal mean PWV compared to a healthy reference population. Chronic hyperglycemia, not T1D duration, is the main predictor of AS in adolescents.

Should mean arterial pressure be included in the definition of ambulatory hypertension in children?

BACKGROUND: The diagnosis of hypertension (HTN)/normotension (NT) on ambulatory blood pressure monitoring (ABPM) is usually based on systolic (SBP) or diastolic blood pressure (DBP). The goal of this study was to analyze whether inclusion of mean arterial pressure (MAP) improves the detection of HTN on ABPM. METHODS: We retrospectively studied ABPM records in 229 children (116 boys, median age = 15.3 years) who were referred for evaluation of HTN. A diagnosis of HTN was made if: (A) MAP or SBP or DBP was ≥ 1.65 SDS (95th percentile); (B) SBP or DBP was ≥ 1.65 SDS (95th percentile), during 24-h or daytime or night-time in both definitions. RESULTS: Using definition A, 46/229 patients had HTN compared to definition B by which only 37/229 patients had HTN (p = 0.001). The level of agreement between the two definitions was very good (kappa = 0.86 ± 0.04), however nine patients (19.5 %) were missed by not using MAP in the definition of HTN. These nine patients had only mild HTN with a median Z score of 1.69. CONCLUSIONS: The inclusion of MAP in the definition of ambulatory HTN significantly increased the number of hypertensive patients. MAP may be very helpful in detecting mild HTN in patients with normal/borderline SBP and DBP.

Arterial HTN in children with T1DM--frequent and not easy to diagnose.

INTRODUCTION: To evaluate the diagnostic efficacy of the office blood pressure (OBP) and ambulatory blood pressure monitoring (ABPM) in the assessment of hypertension (HTN) in children with diabetes mellitus type 1 (T1DM). METHODS: We analyzed OBP and ABPM measurements in 84 diabetic children (43 boys) obtained at a median age of 14.9 yr and 6.3 +/- 3.5 yr after diagnosis of T1DM. OBP and ABPM results were converted into standard deviation scores (SDS). In addition, we analyzed blood pressure loads and nighttime dipping. The comparison between OBP and ABPM was performed using kappa coefficient and receiver operator curve (ROC). RESULTS: HTN was diagnosed in 43/84 (51%) patients using OBP (>95th percentile), and in 24/84 (29%) patients using ABPM ( > or = 95th percentile during 24 h, day or night). Both methods were in agreement in 33 ABPM normotensive and 16 ABPM hypertensive patients (most had nighttime HTN); 32% patients had white-coat HTN and 9.5% patients had masked HTN. The kappa coefficient was 0.175 (95% CI from -0.034 to 0.384) suggesting poor agreement between OBP and ABPM. Diastolic OBP was a better predictor of ABPM HTN (ROC area under the curve (AUC) = 0.71 +/- 0.06) than systolic OBP (AUC = 0.58 +/- 0.07). The percentage of non-dippers ranged from 7 to 23% in ABPM normotensive patients, and 21-42% in ABPM hypertensive patients who also had significantly higher BP loads (p < 0.0001). CONCLUSION: Children with T1DM often suffer from nocturnal, white coat- and masked HTN, which can not be assessed and predicted by the OBP.