Dyslipidemia in children with chronic kidney disease-findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study.

BACKGROUND: Dyslipidemia is an important and modifiable risk factor for CVD in children with CKD. METHODS: In a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3-5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis. RESULTS: A total of 681 patients aged 12.2 ± 3.3 years with a mean eGFR of 26.9 ± 11.6 ml/min/1.73 m2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1 g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure. CONCLUSIONS: Dyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors.

Cognitive performance in children and adolescents with primary hypertension and the role of body mass.

Objective: Primary hypertension has been shown to affect cognitive functions in adults but evidence in the pediatric population remain scarce and equivocal. We aimed to compare cognitive functioning between children diagnosed with primary hypertension and normotensive controls, with a focus on the role of different blood pressure (BP) parameters and body mass. Methods: We conducted a single-center, prospective, cross-sectional study of children and adolescents (6-17 years old) with primary hypertension and age- and sex-matched normotensive controls. All participants underwent office BP, ambulatory BP monitoring (ABPM), and central BP measurements using an oscillometric device. Neurocognitive assessment consisted of evaluation of (i) intelligence quotient (IQ), (ii) categorical and phonemic fluency, (iii) verbal memory (verbal-logical story recall), and (iv) non-verbal computerized cognitive assessment. Results: The study included a total of 59 patients with primary hypertension (14 ± 3 years) and 37 normotensive controls (14 ± 3 years). Participants in the primary hypertension group had a significantly higher body mass index z-score (BMIz: 2.1 ± 1.4 vs. 0.7 ± 0.9, p < 0.001), and 85% received antihypertensive therapy. Participants with primary hypertension showed worse performance in the domains of reaction speed, attention and processing speed, visual memory, new learning, and phonemic fluency. After adjusting for BMIz, only the differences in the reaction speed tasks remained significant. None of the BP parameters was associated with cognitive outcomes after adjustment for age, sex, and BMIz. BMIz associated with tasks of visual memory, new learning, spatial planning, and working memory, independent of age and sex. Conclusion: Children and adolescents diagnosed with primary hypertension exhibit worse performance in the cognitive domains of reaction speed, attention, processing speed, visual memory, and new learning. These differences to healthy controls can be partially attributed to accompanying increase of body mass.

Primary Arterial Hypertension Associated with Cognitive Dysfunction in Young Adults: Results from a Cross-Sectional Controlled Study.

Despite evidence of primary hypertension (PH)-associated cognitive dysfunction in pediatric, middle-aged, and older adult populations, respective data in young adults remains scarce. We aimed to define differences in cognitive performance between individuals with PH and healthy controls in early adulthood. A convenience sample of young adults (age 18-45 years) with PH and their healthy sex, age, education, and household income matched counterparts were cross-sectionally tested for verbal fluency, verbal memory, general intelligence, reaction speed, attention, visual memory, and executive functioning. Between-group differences were determined using Student's t and Mann-Whitney U tests. Sensitivity analysis was performed by adjusting for body mass index (BMI) in analysis of covariance (ANCOVA) and regression models. Thirty-three adults with PH (22, 66.7% male, median age 38.8, interquartile range (IQR) = 33.2-41.6 years) and twenty-two healthy controls (9, 40.9% male, median age 36.1, IQR = 27.5-39.8 years) completed the neuropsychological assessment. Participants with PH performed worse on computerized tasks of reaction time (median response time (Z = -2.019, p = 0.044), median time for release of response button (Z = -2.509, p = 0.012)) and sustained attention (signal detection measure, RVPA (t = 2.373, p = 0.021), false alarms ÷ (false alarms + correct rejections), RVPPFA (Z = -2.052, p = 0.040)). The group variable was not a statistically significant predictor of performance in these domains after adjustment for BMI (p > 0.05). In regression analyses, high office systolic blood pressure (oSBP) was independently associated with poor sustained attention (ßSBP(st.) = -0.283, multiple R2 = 0.252 (RVPA), ßSBP(st.) = 0.551, multiple R2 = 0.386 (RVPPFA)). Young adults with PH were found to perform worse in tasks of response speed and sustained attention. While the difference between neuropsychological evaluation results in PH and control groups was confounded by BMI, oSBP measures were independently related to sustained attention. The selectivity of PH-associated cognitive profile in young adults has to be confirmed in larger trials.

Long-term Effects of Kidney Transplantation Compared With Dialysis on Intima-media Thickness in Children-Results From the 4C-T Study.

BACKGROUND: Children requiring kidney replacement therapy experience high burden of cardiovascular (CV) disease leading to increased mortality. Intima-media thickness (IMT) indicating atherosclerosis is a validated surrogate marker for future CV events. METHODS: We investigated the effect of different treatment modalities (dialysis, preemptive kidney transplantation (KTx), late KTx after dialysis) on IMT by multivariable linear mixed-effect modeling. Patients were enrolled in a prospective cohort study. RESULTS: A total of 261 analyzed children had a mean follow-up of 3 y. Children after preemptive and late KTx had lower levels of IMT when compared with dialysis. Using an interaction term, a significant progression of IMT over time was seen during dialysis (ß = 0.0053 mm/y, P   =  0.004). IMT before the start of therapy was the most influential determinant in all models. Low IMT was associated with maintenance steroid treatment after preemptive KTx. High IMT on dialysis was associated with higher systolic blood pressure, lower body mass index, lower serum albumin, and lower bicarbonate. CONCLUSIONS: IMT remained rather stable in children several years after KTx. In contrast, children on dialysis had higher IMT values, which increased over time. In these children, blood pressure control, calorie and protein intake, and acid-base homeostasis seem important. Taken together, children might profit from early transplantation to limit accumulation of CV risk.

Decline in Left Ventricular Early Systolic Function with Worsening Kidney Function in Children with Chronic Kidney Disease: Insights from the 4C and HOT-KID Studies.

INTRODUCTION: Adults with childhood-onset chronic kidney disease (CKD) have an increased risk of cardiovascular disease. First-phase ejection fraction (EF1), a novel measure of early systolic function, may be a more sensitive marker of left ventricular dysfunction than other markers in children with CKD. OBJECTIVE: To examine whether EF1 is reduced in children with CKD. METHODS: Children from the 4C and HOT-KID studies were stratified according to estimated glomerular filtration rate (eGFR). The EF1 was calculated from the fraction of left ventricular (LV) volume ejected up to the time of peak aortic flow velocity. RESULTS: The EF1 was measured in children ages 10.9 ± 3.7 (mean ± SD) years, 312 with CKD and 63 healthy controls. The EF1 was lower, while overall ejection fraction was similar, in those with CKD compared with controls and decreased across stages of CKD (29.3% ± 3.7%, 23.5% ± 4.5%, 19.8% ± 4.0%, 18.5% ± 5.1%, and 16.7% ± 6.6% in controls, CKD 1, 2, 3, and ≥ 4, respectively, P < .001). The relationship of EF1 to eGFR persisted after adjustment for relevant confounders (P < .001). The effect size for association of measures of LV structure or function with eGFR (SD change per unit change in eGFR) was greater for EF1 (ß = 0.365, P < .001) than for other measures: LV mass index (ß = -0.311), relative wall thickness (ß = -0.223), E/e' (ß = -0.147), and e' (ß = 0.141) after adjustment for confounders in children with CKD. CONCLUSIONS: Children with CKD exhibit a marked and progressive decline in EF1 with falling eGFR. This suggests that EF1 is a more sensitive marker of LV dysfunction when compared to other structural or functional measures and that early LV systolic function is a key feature in the pathophysiology of cardiac dysfunction in CKD.

Development and Integration of Patient-Reported Measures into E-Health System: Pilot Feasibility Study.

Patient-centered care is recognized as a key element in recent healthcare management strategies. However, the integrated collection of patient feedback capturing the entire journey of patients with complex medical conditions remains understudied. Herein, we aimed to describe the development of an instrument prototype for the collection of PROMs and PREMs that would encompass a whole patient journey at a single time point. We further describe the process of its integration into a hospital's information system (HIS) and the results of a pilot feasibility study in adult patients with kidney and hematological diseases. We developed an instrument consisting of original PREM and generic EQ-5D-5L questionnaires. E-questionnaires were handled with REDCap software (version 12.5.14) and integrated into the HIS. Patients refusing to use e-questionnaires (48%) were offered paper administration and were older (64 vs. 50 years). The overall response rate for e-questionnaires was 57.1% with a median completion time of 2.0 and 3.7 min for PROM and PREM, respectively. Psychological and social services and primary care setting (diagnosis establishment and involvement in continuous care) were identified as most problematic. The majority of PREM dimensions encompassing different levels of care significantly correlated with PROM responses. Our data indicate the feasibility and potential relevance of the proposed approach, although wider-scale studies in diverse settings are needed.

Integrated Collection of Patient-Reported Outcomes and Experiences in Children with Kidney and Hematological Diseases: A Pilot Study.

We aimed to explore the feasibility and potential relevance of integrated electronic collection of patient-reported outcome and experience measures (PROM and PREM) in children with special healthcare needs (CSHCN) by using the example of children with kidney and hematological diseases. We performed a cross-sectional, single-center study of children <18 years of age. Children (≥10 years) and their parents received Generic PedsQL Core Scale 4.0 and custom PREM surveys to their email addresses via the REDCap platform, and the results were integrated into the hospital's electronic health records system. A total of 192 patients (98 with kidney diseases and 94 with hematological diseases) were enrolled. The overall response rate was 51%, and the median time for completion of each proxy questionnaire was approximately three minutes. The lowest PROM scores were observed in the emotional and school functioning dimensions. More favorable experiences in the diagnosis establishment process were associated with higher scores in physical, social, school functioning, and total PROM scores. A better evaluation of the hospital's environment was associated with higher social functioning, while better information provision correlated with higher physical functioning and total PROM scores. Our data indicates that integrated electronic collection of PROMs and PREMs in the population of CSHCN is feasible, but efforts to increase the response rate are needed. The associations between PROMs and PREMs suggest that future studies exploring targeted interventions at the healthcare service level to improve subjective patient outcomes are needed.

Stricter Blood Pressure Control Is Associated With Lower Left Ventricular Mass in Children After Kidney Transplantation: A Longitudinal Analysis of the 4C-T Study.

BACKGROUND: We assessed the effect of blood pressure (BP) control on left ventricular mass index (LVMI) and left ventricular hypertrophy (LVH). METHODS: Ninety-six patients (64 males) ≥9 months post-kidney transplantation from the 4C-T (Cardiovascular Comorbidity in Children with Chronic Kidney Disease and Transplantation) study were analyzed longitudinally (mean follow-up, 2.6±1.3 years). Cumulative systolic blood pressure (SBP)/diastolic BP exposure was calculated as a time-averaged area under the curve and categorized: ≤50th, 50th to ≤75th, 75th to ≤90th, and >90th percentile (pct). We performed adjusted linear and logistic mixed models for LVMI and LVH, respectively. RESULTS: At baseline, LVMI was 49.7±12.7g/m2.16 with 64% (n=61) kidney transplantation recipients displaying LVH. Compared with patients with cumulative SBP exposure >90th pct, patients with cumulative SBP of 50th to ≤75th showed a significant LVMI reduction of -5.24g/m2.16 (P=0.007). A similar tendency was seen for cumulative SBP≤50th (ß=-3.70 g/m2.16; P=0.067), but patients with cumulative SBP of 75th to ≤90th pct showed no reduction. A post hoc analysis in patients with cumulative SBP≤75th revealed that median SBP exposure was at 57.5th pct. For cumulative diastolic BP, a significant LVMI reduction was seen in all 3 categories ≤90th pct compared with patients >90th pct. Patients with cumulative SBP of ≤50th or 50th to ≤75th pct showed 79% or 83% lower odds of developing LVH, respectively. Patients with cumulative diastolic BP ≤50th showed a tendency of 82% lower odds for LVH (95% CI, 0.03-1.07). CONCLUSIONS: Stricter BP control led to regression of LVMI and LVH. Our data suggest a BP target below the 60th pct, which needs to be substantiated in a randomized controlled trial.

Shift from severe hypotension to salt-dependent hypertension in a child with autosomal recessive polycystic kidney disease after bilateral nephrectomies: a case report.

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is a significant cause of morbidity and mortality in infants and children. In severe cases bilateral nephrectomies are considered but may be associated with significant neurological complications and life-threatening hypotension. CASE PRESENTATION: We describe a case of a 17 months old boy with genetically confirmed ARPKD who underwent sequential bilateral nephrectomies at the age of 4 and 10 months. Following the second nephrectomy the boy was started on continuous cycling peritoneal dialysis with blood pressure on the lower range. At the age of 12 months after a few days of poor feeding at home the boy experienced a severe episode of hypotension and coma of Glasgow Come Scale of three. Brain magnetic-resonance imaging (MRI) showed signs of hemorrhage, cytotoxic cerebral edema and diffuse cerebral atrophy. During the subsequent 72 h he developed seizures requiring anti-epileptic drug therapy, gradually regained consciousness but remained significantly hypotensive after discontinuation of vasopressors. Thus, he received high doses of sodium chloride orally and intraperitoneally as well as midodrine hydrochloride. His ultrafiltration (UF) was targeted to keep him in mild-to-moderate fluid overload. After two months of stable condition the patient started to develop hypertension requiring four antihypertensive medications. After optimizing peritoneal dialysis to avoid fluid overload and discontinuation of sodium chloride the antihypertensives were discontinued, but hyponatremia with hypotensive episodes reoccurred. Sodium chloride was reintroduced resulting in recurrent salt-dependent hypertension. CONCLUSIONS: Our case report illustrates an unusual course of blood pressure changes following bilateral nephrectomies in an infant with ARPKD and the particular importance of tight regulation of sodium chloride supplementation. The case adds to the scarce literature about clinical sequences of bilateral nephrectomies in infants, and as well highlights the challenge of managing blood pressure in these patients. Further research on the mechanisms and management of blood pressure control is clearly needed.

Urinary DKK3 as a biomarker for short-term kidney function decline in children with chronic kidney disease: an observational cohort study.

BACKGROUND: Childhood-onset chronic kidney disease is a progressive condition that can have a major effect on life expectancy and quality. We evaluated the usefulness of the kidney tubular cell stress marker urinary Dickkopf-related protein 3 (DKK3) in determining the short-term risk of chronic kidney disease progression in children and identifying those who will benefit from specific nephroprotective interventions. METHODS: In this observational cohort study, we assessed the association between urinary DKK3 and the combined kidney endpoint (ie, the composite of 50% reduction of the estimated glomerular filtration rate [eGFR] or progression to end-stage kidney disease) or the risk of kidney replacement therapy (ie, dialysis or transplantation), and the interaction of the combined kidney endpoint with intensified blood pressure reduction in the randomised controlled ESCAPE trial. Moreover, urinary DKK3 and eGFR were quantified in children aged 3-18 years with chronic kidney disease and urine samples available enrolled in the prospective multicentre ESCAPE (NCT00221845; derivation cohort) and 4C (NCT01046448; validation cohort) studies at baseline and at 6-monthly follow-up visits. Analyses were adjusted for age, sex, hypertension, systolic blood pressure SD score (SDS), BMI SDS, albuminuria, and eGFR. FINDINGS: 659 children were included in the analysis (231 from ESCAPE and 428 from 4C), with 1173 half-year blocks in ESCAPE and 2762 in 4C. In both cohorts, urinary DKK3 above the median (ie, >1689 pg/mg creatinine) was associated with significantly greater 6-month eGFR decline than with urinary DKK3 at or below the median (-5·6% [95% CI -8·6 to -2·7] vs 1·0% [-1·9 to 3·9], p<0·0001, in ESCAPE; -6·2% [-7·3 to -5·0] vs -1·5% [-2·9 to -0·1], p<0·0001, in 4C), independently of diagnosis, eGFR, and albuminuria. In ESCAPE, the beneficial effect of intensified blood pressure control was limited to children with urinary DKK3 higher than 1689 pg/mg creatinine, in terms of the combined kidney endpoint (HR 0·27 [95% CI 0·14 to 0·55], p=0·0003, number needed to treat 4·0 [95% CI 3·7 to 4·4] vs 250·0 [66·9 to ∞]) and the need for kidney replacement therapy (HR 0·33 [0·13 to 0·85], p=0·021, number needed to treat 6·7 [6·1 to 7·2] vs 31·0 [27·4 to 35·9]). In 4C, inhibition of the renin-angiotensin-aldosterone system resulted in significantly lower urinary DKK3 concentrations (least-squares mean 12 235 pg/mg creatinine [95% CI 10 036 to 14 433] in patients not on angiotensin-converting enzyme inhibitors or angiotensin 2 receptor blockers vs 6861 pg/mg creatinine [5616 to 8106] in those taking angiotensin-converting enzyme inhibitors or angiotensin 2 receptor blockers, p<0·0001). INTERPRETATION: Urinary DKK3 indicates short-term risk of declining kidney function in children with chronic kidney disease and might allow a personalised medicine approach by identifying those who benefit from pharmacological nephroprotection, such as intensified blood pressure lowering. FUNDING: None.

Determinants of Patient-Perceived Primary Healthcare Quality in Lithuania.

Patient-centered care is considered to be one of the essential pillars of a modern healthcare system. Thus, quality assessment based on patients' perceptions, views and experiences in their journey through the healthcare system is recognized as one of the key principles for quality improvement initiatives. Measuring patient satisfaction can be confounded by expectations and prior experiences, which can be at least partly overcome by evaluating patient-perceived healthcare quality (PPHQ). Understanding the principal constituents of PPHQ may aid healthcare professionals and decision makers in the healthcare management process and help in creating instruments to meaningfully measure patient feedback. Herein, we aimed to analyze the primary determinants of PPHQ and their interactions, with a focus on patient experiences and healthcare accessibility, using the example of Lithuanian primary healthcare. For this purpose, we conducted a cross-sectional representative telephone survey that included a total of 1033 respondents (48% male) who had encountered primary healthcare during last 3 years. Survey questions consisted of sociodemographic characteristics, patient perceptions of healthcare service provision, patient experiences, self-reported health status and overall PPHQ ranked with a 5-point Likert scale as the primary outcome. The classification-regression tree (CRT) technique was used to analyze the relationship between different explanatory variables and PPHQ, as well as their relative importance and interactions. The majority of respondents (89%) evaluated PPHQ as acceptable or good. CRT analysis identified staff behavior, organizational accessibility and financial accessibility as the most important factors affecting PPHQ. Importantly, the latter factors surpassed the effect of other known PPHQ determinants, such as sociodemographic characteristics or health status. Further analysis has revealed that the relative importance of staff behavior, including understanding, attention and empathy, increased when more problems with organizational accessibility were encountered. In conclusion, our study suggests that PPHQ in primary healthcare may primarily be determined by organizational and financial accessibility and staff behavior, which may also act as an important mediating factor.

Systolic and diastolic left ventricular function in children with primary hypertension: a systematic review and meta-analysis.

OBJECTIVE: Evaluation of left ventricular function provides early evidence of target-organ damage in children with primary hypertension. We performed a systematic review and meta-analysis of left ventricular systolic and diastolic function in children and adolescents with primary hypertension. METHODS: Literature search was performed in PubMed database and out of 718 articles (published between 2000 and 2021) 22 studies providing comparison of left ventricular function parameters between children with primary hypertension and normotensive controls were selected. RESULTS: Overall, 3460 children (5-21 years) with primary hypertension were analyzed. Meta-analysis showed that hypertensive patients when compared with normotensives, had an increased heart rate (mean difference [MD] 5.59; 95% confidence interval [CI] 3.28, 7.89; 10 studies) and increased fractional shortening (MD 1.04; 95% CI 0.48, 1.60; 9 studies) but did not differ in ejection fraction (MD -0.03; 95% CI -1.07, 1.02; 12 studies). Stroke volume was higher in one out of three studies, whereas no differences in cardiac output were found in two studies with available data. Hypertensive children had also lower E/A values (MD -0.21; -0.33, -0.09; 14 studies), greater values of E/e' (MD 0.59; 0.36, 0.82; 8 studies) and greater global longitudinal stress (MD 2.50; 2.03, 2.96; 4 studies) when compared to those with normotension. CONCLUSION: Our results indicate that hypertensive children and adolescents present with signs of hyperkinetic function of the left ventricle, demonstrate evidence of increased left ventricular strain and impaired diastolic function compared to normotensive controls.

Nutritional and Anthropometric Indices in Children Receiving Haemodiafiltration vs Conventional Haemodialysis - The HDF, Heart and Height (3H) Study.

BACKGROUND: The "HDF-Heart-Height" study showed that haemodiafiltration (HDF) is associated with improved growth compared to conventional haemodialysis (HD). We report a post-hoc analysis of this study assessing the effect of extracorporeal dialysis therapies on nutritional indices. METHODS: 107 children were included in the baseline cross-sectional analysis, of whom 79 (43 HD, 36 HDF) completed the 12-month follow-up. Height (Ht), optimal 'dry' weight (Wt), and body mass index (BMI) standard deviations scores (SDS), waist-to-hip ratio, des-acyl ghrelin (DAG), adiponectin, leptin, insulin-like growth factor-1 (IGF-1)-SDS and insulin were measured. RESULTS: The levels of nutritional indices were comparable between HDF and HD patients at baseline and 12-month. On univariable analyses Wt-SDS positively correlated with leptin and IGF-1-SDS, and negatively with DAG, while Ht-SDS of the overall cohort positively correlated with IGF1-SDS and inversely with DAG and adiponectin. On multivariable analyses, higher 12-month Ht-SDS was inversely associated with baseline DAG (beta = -0.13 per 500 higher; 95%CI -0.22, -0.04; P = .004). Higher Wt-SDS at 12-month was positively associated with HDF modality (beta = 0.47 vs HD; 95%CI 0.12-0.83; P = .01) and inversely with baseline DAG (beta = -0.18 per 500 higher; 95%CI -0.32, -0.05; P = .006). Growth Hormone (GH) treated patients receiving HDF had higher annualized increase in Ht SDS compared to those on HD. CONCLUSIONS: In children on HD and HDF both Wt- and Ht-SDS independently correlated with lower baseline levels of the anorexygenic hormone DAG. HDF may attenuate the resistance to GH, but further studies are required to examine the mechanisms linking HDF to improved growth.

Kidney length normative values - new percentiles by age and body surface area in Central European children and adolescents.

BACKGROUND: Kidney size evaluation is an essential examination in pediatric nephrology. While body length/height is the best predictor of kidney length, age-based and body surface area (BSA)-based normative values may be useful in clinical practice or research. This study aimed to establish ultrasound-based kidney length lambda-mu-sigma (LMS) percentiles by age and BSA in healthy children. METHODS: In 1758 Polish and Lithuanian children (868 boys, 49%) aged 0-19 years, kidney length was measured using ultrasonography. In all participants, anthropometric measurements were taken and kidney function was evaluated based on serum creatinine concentration. Participants with chronic or kidney diseases, abnormal kidney function, or pathologies in sonographic examination were excluded from the analysis. RESULTS: Kidney length (median kidney length) increased progressively from infancy to the age of 18 years, from 60.1 to 114.2 mm in males, and from 57.3 to 105.2 mm in females. A gradual increase of kidney length (50th percentile) in relation to BSA (from 46.1 mm in infants with a BSA of 0-1.2 m2 to 118.3 mm in adolescents with a BSA of 2.6-2.8 m2) was also observed. LMS percentiles by age (stratified by sex) and BSA were determined and presented as graphs and tables of percentiles and LMS parameters by 1-year age intervals and 0.2 m2 of BSA, respectively. CONCLUSIONS: We present the first age- and BSA-based kidney length LMS normative values based on the largest pediatric cohort to date, which can be used in both clinical practice and research studies. A higher resolution version of the Graphical abstract is available as Supplementary information.

Knowledge gaps and future directions in cognitive functions in children and adolescents with primary arterial hypertension: A systematic review.

Arterial hypertension (AH) among adults is known to be associated with worse cognitive outcomes. Similarly, children and adolescents with AH could be expected to underperform during neuropsychological evaluations when compared with healthy peers. Our aims were to review the existing literature on cognitive functioning among children and adolescents with primary AH and to identify what additional evidence may be needed to substantiate the impact of hypertension on poor cognitive outcomes in this population. We conducted a systematic review of articles in PubMed and Web of Science published before 17 January 2022, reporting on cognitive testing among children and adolescents with primary AH. From 1,316 records, 13 were included in the review-7 used battery-testing while other employed indirect measures of cognitive functions. Most of the studies reported worse results among individuals with AH. Results of two prospective trials suggested that cognitive functioning may improve after starting antihypertensive treatment. Ambulatory blood pressure monitoring was shown to be more strongly related to cognitive testing results than office measures of blood pressure. Significant confounders, namely obesity and sleep apnea, were identified throughout the studies. Our review indicates that evidence relating AH with poor cognitive functioning among youth is usually based on indirect measures of executive functions (e.g., questionnaires) rather than objective neuropsychological tests. Future prospective trials set to test different cognitive domains in children and adolescents undergoing treatment for AH are endorsed and should consider using standardized neuropsychological batteries as well as adjust the assessing results for obesity and sleep disorders.

Pharmacological Treatment of Arterial Hypertension in Children and Adolescents in Lithuania.

The global prevalence of arterial hypertension (AH) in the pediatric population is increasing, but therapeutic approaches and the choice of the most suitable antihypertensive medications remains challenging. The study aimed to estimate the prevalence, treatment rates, and pharmacological treatment patterns of children and adolescents with AH in Lithuania during 2019 using real-world data. The study population consisted of citizens of Lithuania aged 0 to 17 years, who were diagnosed with AH according to the International Classification of Diseases (ICD). The analysis of reimbursed antihypertensive medication prescriptions was performed according to AH etiology and age. The overall prevalence of AH by diagnostic ICD codes in 2019 was 0.29%:0.24% for primary and 0.05% for secondary. Treatment rates were 39.8% for primary AH and 66.3% for secondary AH. Angiotensin-converting enzyme inhibitors (ACEi) were the most popular medications irrespective of the etiology of AH or age. Beta-blockers were in the second place and used more often in older children. Calcium channel blockers were the third and angiotensin receptor blockers were the fourth most frequent choices. Enalapril was the most popular agent in the ACEi group and metoprolol in the beta-blocker group. Nearly forty percent of Lithuanian children with primary AH receive pharmacological therapy compared to two-thirds with secondary AH. Although ACEi are the predominant class of antihypertensive medications, discordances with available guidelines are evident, particularly in the overuse of beta-blockers and underuse of diuretics.

Prevalence of left ventricular hypertrophy in children and young people with primary hypertension: Meta-analysis and meta-regression.

Background: Left ventricular hypertrophy (LVH) is the main marker of HMOD in children and young people (CYP). We aimed to assess the prevalence of LVH and its determinants in CYP with primary hypertension (PH). Methods: A meta-analysis of prevalence was performed. A literature search of articles reporting LVH in CYP with PH was conducted in Medline, Embase, and Cochrane databases. Studies with a primary focus on CYP (up to 21 years) with PH were included. Meta-regression was used to analyze factors explaining observed heterogeneity. Results: The search yielded a total of 2,200 articles, 153 of those underwent full-text review, and 47 reports were included. The reports evaluated 51 study cohorts including 5,622 individuals, 73% male subjects, and a mean age of 13.6 years. LVH was defined as left ventricle mass index (LVMI) ≥ 95th percentile in 22 (47%), fixed cut-off ≥38.6 g/m2.7 in eight (17%), sex-specific fixed cut-off values in six (13%), and miscellaneously in others. The overall prevalence of LVH was 30.5% (95% CI 27.2-33.9), while heterogeneity was high (I 2 = 84%). Subgroup analysis including 1,393 individuals (76% male subjects, mean age 14.7 years) from pediatric hypertension specialty clinics and LVH defined as LVMI ≥95th percentile only (19 study cohorts from 18 studies), reported prevalence of LVH at 29.9% (95% CI 23.9 to 36.3), and high heterogeneity (I 2 = 84%). Two studies involving patients identified through community screening (n = 1,234) reported lower LVH prevalence (21.5%). In the meta-regression, only body mass index (BMI) z-score was significantly associated with LVH prevalence (estimate 0.23, 95% CI 0.08-0.39, p = 0.004) and accounted for 41% of observed heterogeneity, but not age, male percentage, BMI, or waist circumference z-score. The predominant LVH phenotype was eccentric LVH in patients from specialty clinics (prevalence of 22% in seven studies with 779 participants) and one community screening study reported the predominance of concentric LVH (12%). Conclusion: Left ventricular hypertrophy is evident in at least one-fifth of children and young adults with PH and in nearly a third of those referred to specialty clinics with a predominant eccentric LVH pattern in the latter. Increased BMI is the most significant risk association for LVH in hypertensive youth.

Arterial Stiffness and Chronic Kidney Disease Progression in Children.

BACKGROUND AND OBJECTIVES: CKD has been linked to increased arterial stiffness in adults, but data in children with CKD remain conflicting. We aimed to investigate the longitudinal dynamics and determinants of pulse wave velocity in children with CKD and its association with CKD progression. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed an analysis of the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study, which prospectively followed children aged 6-17 years with CKD stages 3-5. Follow-up was censored at the time of KRT initiation. Two separate analyses were performed: with absolute pulse wave velocity (primary outcome) and with pulse wave velocity standardized to height (z score; restricted to participants ≤17 years) as a sensitivity analysis. RESULTS: In total, 667 patients with a mean baseline eGFR of 27 ml/min per 1.73 m2 were included. Pulse wave velocity above the 95th percentile was observed in 124 (20%) patients at baseline. Absolute pulse wave velocity increased gradually over the median follow-up of 2.7 (interquartile range, 0.7-4.4) years, whereas pulse wave velocity z score remained relatively stable. Absolute pulse wave velocity over time associated with time; older age; higher mean arterial pressure, LDL cholesterol, and albuminuria; and lower ferritin. Pulse wave velocity z score (n=628) was associated with the same variables and additionally, with higher diastolic BP z score, lower height z score, younger age, and girls. Of 628 patients, 369 reached the composite end point of CKD progression (50% eGFR loss, eGFR <10 ml/min per 1.73 m2, or the start of KRT) during a median follow-up of 2.4 (interquartile range, 0.9-4.6) years. Pulse wave velocity z score did not associate with CKD progression by univariable or multivariable proportional hazard analysis correcting for the established predictors eGFR, proteinuria, and BP. CONCLUSIONS: Pulse wave velocity is increased in children with CKD but does not associate with eGFR or CKD progression.

Disparities between determinants of impaired vascular structure and function in young people with primary hypertension: a systematic review.

OBJECTIVE: Early effects of primary hypertension on arterial structure and function in children and young people (CYP) and their determinants remain elusive. We aimed to review independent determinants of carotid intima-media thickness (cIMT), carotid wall cross-sectional area (WCSA) and carotid-femoral pulse wave velocity (cfPWV) in CYP with primary hypertension. METHODS: We performed a systematic review of studies reporting multivariable analysis of cfPWV, cIMT and WCSA in CYP (up to 25 years of age) with primary hypertension. Literature search was performed in PubMed database and 13, 12 and two articles including 3860 (age range 4-25 years, 50% male individuals), 2038 children (5-25 years, 55% male individuals) and 136 children (5-17 years, 85% male individuals) were selected for final analysis of cfPWV, cIMT and WCSA, respectively. RESULTS: Ninety and 86% of the studies reported higher cfPWV and cIMT in CYP with elevated blood pressure (BP) compared with normotensive controls. Different indices of BP were positively associated with cfPWV in 92% of studies, whereas BMI showed association in 31%. Carotid IMT associated with BP indices in 50% and with BMI in 25% of the studies. WCSA was studied longitudinally and its improvement associated with decrease in measures of central obesity. CONCLUSION: We found a disparity between the determinants of structural and functional impairment of arterial tree in CYP with primary hypertension. In contrast to cIMT and WCSA, increase of cfPWV is almost exclusively determined by BP.