Significance Statement: Although studies suggest that hemodiafiltration (HDF) may reduce cardiovascular mortality in adults, data in children are sparse. In this observational multicenter study, the authors compared HDF and hemodialysis (HD) in children with ESKD, finding that annualized changes in well validated subclinical markers of cardiovascular disease, including carotid intima-media thickness SD scores, were lower in HDF and associated with lower 24-hour ambulatory BP and intradialytic weight gain. Height increased only in the HDF cohort. Compared with the HD cohort, the HDF cohort also had better self-reported outcomes, with fewer headaches, less dizziness or cramps, and shorter recovery time after dialysis sessions. The study provides proof-of-concept data that HDF is a safe treatment that may have benefits over conventional HD in children. A randomized trial is required to confirm these findings. Background: Hypertension and cardiovascular disease are common in children undergoing dialysis. Studies suggest that hemodiafiltration (HDF) may reduce cardiovascular mortality in adults, but data for children are scarce. Methods: The HDF, Heart and Height study is a nonrandomized observational study comparing outcomes on conventional hemodialysis (HD) versus postdilution online HDF in children. Primary outcome measures were annualized changes in carotid intima-media thickness (cIMT) SD score and height SD score. Results: We enrolled 190 children from 28 centers; 78 on HD and 55 on HDF completed 1-year follow-up. The groups were comparable for age, dialysis vintage, access type, dialysis frequency, blood flow, and residual renal function. At 1 year, cIMT SD score increased significantly in children on HD but remained static in the HDF cohort. On propensity score analysis, HD was associated with a +0.47 higher annualized cIMT SD score compared with HDF. Height SD score increased in HDF but remained static in HD. Mean arterial pressure SD score increased with HD only. Factors associated with higher cIMT and mean arterial pressure SD-scores were HD group, higher ultrafiltration rate, and higher β2-microglobulin. The HDF cohort had lower β2-microglobulin, parathyroid hormone, and high-sensitivity C-reactive protein at 1 year; fewer headaches, dizziness, or cramps; and shorter postdialysis recovery time. Conclusions: HDF is associated with a lack of progression in vascular measures versus progression with HD, as well as an increase in height not seen in the HD cohort. Patient-related outcomes improved among children on HDF correlating with improved BP control and clearances. Confirmation through randomized trials is required.

Background: Currently used pediatric kidney length normative values are based on small single-center studies, do not include kidney function assessment, and focus mostly on newborns and infants. We aimed to develop ultrasound-based kidney length normative values derived from a large group of European Caucasian children with normal kidney function. Methods: Out of 1,782 children aged 0–19 years, 1,758 individuals with no present or past kidney disease and normal estimated glomerular filtration rate had sonographic assessment of kidney length. The results were correlated with anthropometric parameters and estimated glomerular filtration rate. Kidney length was correlated with age, height, body surface area, and body mass index. Height-related kidney length curves and table were generated using the LMS method. Multivariate regression analysis with collinearity checks was used to evaluate kidney length predictors. Results: There was no significant difference in kidney size in relation to height between boys and girls. We found significant (p < 0.001), but clinically unimportant (Cohen’s D effect size = 0.04 and 0.06) differences between prone vs. supine position (mean paired difference = 0.64 mm, 95% CI = 0.49–0.77) and left vs. right kidneys (mean paired difference = 1.03 mm, 95% CI = 0.83–1.21), respectively. For kidney length prediction, the highest coefficient correlation was observed with height (adjusted R² = 0.87, p < 0.0001). Conclusions: We present height-related LMS-percentile curves and tables of kidney length which may serve as normative values for kidney length in children from birth to 19 years of age. The most significant predictor of kidney length was statural height. Graphic

Background Central systolic and pulse pressures are stronger predictors of cardiovascular risk and hypertensive organ damage than brachial blood pressure. It is suggested that isolated systolic hypertension typically seen in adolescents is associated with normal central blood pressure and does not lead to organ damage and this phenomenon is called spurious hypertension. Methods We assessed the prevalence of spurious hypertension and analyzed utility of pulse wave analysis as determinant of hypertensive organ damage in 294 children (62 girls; 15.0 ± 2.4 years) diagnosed as primary hypertension. White coat hypertension, ambulatory prehypertension, ambulatory hypertension, and severe ambulatory hypertension were diagnosed in 127, 29, 41, and 97 patients, respectively. Results Normal central blood pressure was found in 100% in patients with white coat hypertension, 93% in pre-hypertensives, 51.2% in those with ambulatory hypertension, and 27.8% with severe ambulatory hypertension (p = 0.0001). Children with severe ambulatory hypertension had higher central systolic and pulse pressure, pulse wave velocity, and greater prevalence of left ventricular hypertrophy than white coat and prehypertensive children (p < 0.05). Left ventricular mass index and carotid intima-media thickness correlated with central systolic and pulse pressure (p < 0.05 for all). Receiver operating curve area was similar for augmentation pressure (0.5836), 24-h ambulatory systolic blood pressure (0.5841), central systolic blood pressure (0.6090), and central pulse pressure (0.5611) as predictors of left ventricular hypertrophy. Conclusions These findings suggest that pulse wave analysis is complementary to ambulatory blood pressure monitoring in assessment of risk of organ damage in hypertensive adolescents.

Although the importance of office prehypertension/high normal blood pressure (BP) has been well documented, the significance of ambulatory prehypertension (AmbPreHT) has not been determined. We analyzed markers of target organ damage and hemodynamics in adolescents with AmbPreHT in comparison with hypertensive and normotensive subjects. Out of 304 white patients aged 15.0±2.5 years with office hypertension, 30 children had AmbPreHT and were compared with 66 normotensive healthy children and 92 children with true hypertension (elevated office, ambulatory, and central BP), 22 had ambulatory hypertension (AmbHT), and 70 had severe AmbHT (SevAmbHT). Stroke volume and cardiac output were greater in AmbPreHT compared with patients with normotension but did not differ between AmbPreHT, AmbHT, and SevAmbHT. Similarly, AmbPreHT, AmbHT, and SevAmbHT had similar total peripheral resistance, lower than patients with normotension ( P <0.05). Central systolic BP was higher in patients with AmbPreHT, AmbHT, and SevAmbHT compared with normotensives ( P <0.01). In all 3 groups, the carotid intima-media thickness Z scores were significantly higher than in normotensive ( P <0.001). AmbPreHT and AmbHT patients had higher left ventricular mass index and prevalence of left ventricular hypertrophy compared with normotensive but lower compared with SevAmbHT ( P <0.001). Pulse wave velocity Z scores were increased in patients with AmbPreHT, AmbHT, and SevAmbHT compared with patients with normotension ( P <0.01). Multiple regression analysis showed that body mass index Z score, central systolic BP, and uric acid levels were significant independent predictors of left ventricular mass index. In conclusion, patients with AmbPreHT presented similar cardiovascular adaptations to those observed in patients with hypertensive and may be at risk of developing cardiovascular events.

Protein-bound uremic toxins (PBUTs) play a role in the multisystem disease that children on hemodialysis (HD) are facing, but little is known about their levels and protein binding (%PB). In this study, we evaluated the levels and %PB of six PBUTs cross-sectionally in a large pediatric HD cohort (n = 170) by comparing these with healthy and non-dialysis chronic kidney disease (CKD) stage 4–5 (n = 24) children. In parallel β2-microglobulin (β2M) and uric acid (UA) were evaluated. We then explored the impact of age and residual kidney function on uremic toxin levels and %PB using analysis of covariance and Spearman correlation coefficients (r_s). We found higher levels of β2M, p-cresyl glucuronide (pCG), hippuric acid (HA), indole acetic acid (IAA), and indoxyl sulfate (IxS) in the HD compared to the CKD4–5 group. In the HD group, a positive correlation between age and pCG, HA, IxS, and pCS levels was shown. Residual urine volume was negatively correlated with levels of β2M, pCG, HA, IAA, IxS, and CMPF (r_s −0.2 to −0.5). In addition, we found overall lower %PB of PBUTs in HD versus the CKD4–5 group, and showed an age-dependent increase in %PB of IAA, IxS, and pCS. Furhtermore, residual kidney function was overall positively correlated with %PB of PBUTs. In conclusion, residual kidney function and age contribute to PBUT levels and %PB in the pediatric HD population.

Background: The relationship between circulating regulatory T-cell (Tregs) subset distribution and hypertension severity in children with primary hypertension is not known. We aimed to find out if target organ damage (TOD) in children with primary hypertension is related to defects in Tregs distribution reflected by their phenotype characteristics. Methods: The study constituted 33 nontreated hypertensive children and 35 sex-matched and age-matched controls. Using multicolor flow cytometry technique, we assessed a distribution of the total Tregs (CD4⁺CD25^highCD127^low/−) and their subsets (CD45RA⁺-naive Tregs, CD45RA⁻ memory/activated Tregs, CD45RA⁺CD31⁺ recent thymic emigrants Tregs and mature naive CD45RA⁺CD31⁻ Tregs) in the whole blood. Results: Hypertensive children showed decreased percentage of the total Tregs, the CD45RA⁺-naive Tregs, the total CD31⁺ Tregs and the recent thymic emigrants Tregs but elevation of the CD45RA⁻ memory/activated Treg and mature naive CD45RA⁺CD31⁻ Tregs. Decreased frequency of the total Tregs, naive Tregs and CD31⁺-bearing Treg cell subsets (CD31⁺ total Tregs, CD45RA⁺CD31⁺ recent thymic emigrants Tregs) negatively correlated to TOD markers, arterial stiffness and blood pressure elevation. In contrast, increased percentage of memory Tregs and CD31⁻ Tregs subsets positively correlated to organ damage markers, arterial stiffness and blood pressure values. These changes were independent of BMI, age, sex and hsCRP. Conclusion: Both diagnosis of hypertension, TOD and arterial stiffness in hypertensive children were associated with decreased population of total CD4⁺ Tregs, limited output of recent thymic emigrants Tregs, and increased pool of activated/memory Tregs. Hypertension was an independent predictor of the circulating Treg subsets distribution irrespective of hsCRP.