Publications by authors named "Mieczyslaw Litwin"

113 Publications

Hemodiafiltration maintains a sustained improvement in blood pressure compared to conventional hemodialysis in children-the HDF, heart and height (3H) study.

Pediatr Nephrol 2021 Feb 24. Epub 2021 Feb 24.

University College London Great Ormond Street Hospital for Children and Institute of Child Health, London, UK.

Background: Hypertension is prevalent in children on dialysis and associated with cardiovascular disease. We studied the blood pressure (BP) trends and the evolution of BP over 1 year in children on conventional hemodialysis (HD) vs. hemodiafiltration (HDF).

Methods: This is a post hoc analysis of the "3H - HDF-Hearts-Height" dataset, a multicenter, parallel-arm observational study. Seventy-eight children on HD and 55 on HDF who had three 24-h ambulatory BP monitoring (ABPM) measures over 1 year were included. Mean arterial pressure (MAP) was calculated and hypertension defined as 24-h MAP standard deviation score (SDS) ≥95th percentile.

Results: Poor agreement between pre-dialysis systolic BP-SDS and 24-h MAP was found (mean difference - 0.6; 95% limits of agreement -4.9-3.8). At baseline, 82% on HD and 44% on HDF were hypertensive, with uncontrolled hypertension in 88% vs. 25% respectively; p < 0.001. At 12 months, children on HDF had consistently lower MAP-SDS compared to those on HD (p < 0.001). Over 1-year follow-up, the HD group had mean MAP-SDS increase of +0.98 (95%CI 0.77-1.20; p < 0.0001), whereas the HDF group had a non-significant increase of +0.15 (95%CI -0.10-0.40; p = 0.23). Significant predictors of MAP-SDS were dialysis modality (β = +0.83 [95%CI +0.51 - +1.15] HD vs. HDF, p < 0.0001) and higher inter-dialytic-weight-gain (IDWG)% (β = 0.13 [95%CI 0.06-0.19]; p = 0.0003).

Conclusions: Children on HD had a significant and sustained increase in BP over 1 year compared to a stable BP in those on HDF, despite an equivalent dialysis dose. Higher IDWG% was associated with higher 24-h MAP-SDS in both groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-021-04930-2DOI Listing
February 2021

Remodeling of Retinal Microcirculation Is Associated With Subclinical Arterial Injury in Hypertensive Children.

Hypertension 2021 Feb 15:HYPERTENSIONAHA12016734. Epub 2021 Feb 15.

Department of Nephrology and Arterial Hypertension, The Children's Memorial Health Institute, Warsaw, Poland. (L.O., C.K., M.L.).

The aim of the study was to assess the relationship between hypertensive target organ damage and vessel density (VD), foveal thickness, thickness of retinal nerve fiber layer, ganglion cell complex, and foveal avascular zone (FAZ) using optical coherence tomography angiography in a nonselected group of hypertensive children. One hundred fifty-seven children (56 girls) in mean age 14.9±2.9 years, in whom arterial hypertension was ultimately diagnosed were included in the study. FAZ, whole, fovea, parafovea superficial VD, whole, fovea, parafovea deep VD, foveal thickness, retinal nerve fiber layer, and ganglion cell complex were taken into analysis. Both absolute and standardized values of carotid intima-media thickness correlated with the larger FAZ area (=0.035, =0.17; =0.01, =0.2, respectively). Subjects with increased carotid intima-media thickness had significantly larger FAZ (=0.024), reduced fovea superficial VD (=0.039), and foveal thickness (=0.007). Left ventricular hypertrophy and increased carotid-femoral pulse wave velocity were not associated with optical coherence tomography angiography parameters. Multiple linear regression revealed that the only determinant of FAZ and foveal thickness was higher carotid intima-media thickness-SD score, and for fovea superficial VD, the only determinant was central systolic blood pressure. In conclusion, hypertensive children present with signs of remodeling of microcirculation and decreased neural layer of retina associated with hypertensive macrocirculation remodeling expressed as increased carotid intima-media thickness and elevated central systolic blood pressure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16734DOI Listing
February 2021

Analysis of vitamin D metabolites in survivors of infantile idiopathic hypercalcemia caused by CYP24A1 mutation or SLC34A1 mutation.

J Steroid Biochem Mol Biol 2021 Jan 28;208:105824. Epub 2021 Jan 28.

Department of Nephrology and Arterial Hypertension, The Children's Memorial Health Institute, Warsaw, Poland. Electronic address:

Infantile hypercalcemia (IH), is a rare disorder caused by CYP24A1 or SLC34A1 variants which lead to disturbed catabolism of 25(OH)D and 125(OH)D or increased generation of 125(OH)D.

Aim Of Study: To assess the status of 2425(OH)D and other markers of vitamin D in IH survivors, in whom variants of CYP24A1 or SLC34A1 gene were found and to compare these unique biochemical features with those obtained from subjects who were diagnosed in the first year of life with hypercalcemia, elevated 25(OH)D and low PTH but in whom neither CYP24A1 nor SLC34A1 variant was found.

Patients And Methods: 16 IH survivors in whom CYP24A1 (n = 13) or SLC34A1 (n = 3) variants were found and 41 subjects in whom hypercalcemia was diagnosed in the first year of life but in whom CYP24A1 or SLC34A1 variants were not found were included in the study. 25(OH)D, 3-epi-25(OH)D, 25(OH)D, 2425(OH)D were assessed by liquid chromatography coupled with tandem mass spectrometry. 125(OH)D concentrations were assessed by chemiluminescence.

Results: Subjects with CYP24A1 variants, despite normal 25(OH)D levels, had higher 25(OH)D/2425(OH)D ratio values (487; 265-1073 ng/mL) when compared to subjects with SLC34A1 variants (16; 16-23 ng/mL) and with subjects in whom CYP24A1 or SLC34A1 were not found (56; 9-56 ng/mL) (p = 0.00003). Separation of interfering metabolite further increased differences between subjects with and without CYP24A1 mutation.

Conclusions: Survivors of IH with CYP24A1 variant, despite being normocalcemic, still presented extremely high 25(OH)D/2425(OH)D ratio values. Separation of interfering compound further increased differences between subjects with CYP24A1 mutation and without this mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsbmb.2021.105824DOI Listing
January 2021

Long-term outcome of the survivors of infantile hypercalcaemia with CYP24A1 and SLC34A1 mutations.

Nephrol Dial Transplant 2020 Oct 25. Epub 2020 Oct 25.

Department of Nephrology, Kidney Transplantation and Arterial Hypertension, Children's Memorial Health Institute, Warsaw, Poland.

Background: Infantile hypercalcaemia (IH) is a vitamin D3 metabolism disorder. The molecular basis for IH is biallelic mutations in the CYP24A1 or SLC34A1 gene. These changes lead to catabolism disorders (CYP24A1 mutations) or excessive generation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (SLC34A1 mutations). The incidence rate of IH in children and the risk level for developing end-stage renal disease (ESRD) are still unknown. The aim of this study was to analyse the long-term outcome of adolescents and young adults who suffered from IH in infancy.

Design: Forty-two children (23 girls; average age 10.7 ± 6.3 years) and 26 adults (14 women; average age 24.2 ± 4.4 years) with a personal history of hypercalcaemia with elevated 1,25(OH)2D3 levels were included in the analysis. In all patients, a genetic analysis of possible IH mutations was conducted, as well as laboratory tests and renal ultrasonography.

Results: IH was confirmed in 20 studied patients (10 females). CYP24A1 mutations were found in 16 patients (8 females) and SLC34A1 in 4 patients (2 females). The long-term outcome was assessed in 18 patients with an average age of 23.8 years (age range 2-34). The average glomerular filtration rate (GFR) was 72 mL/min/1.73 m2 (range 15-105). Two patients with a CYP24A1 mutation developed ESRD and underwent renal transplantation. A GFR <90 mL/min/1.73 m2 was found in 14 patients (77%), whereas a GFR <60 mL/min/1.73 m2 was seen in 5 patients (28%), including 2 adults after renal transplantation. Three of 18 patients still had serum calcium levels >2.6 mmol/L. A renal ultrasound revealed nephrocalcinosis in 16 of 18 (88%) patients, however, mild hypercalciuria was detected in only one subject.

Conclusions: Subjects who suffered from IH have a greater risk of progressive chronic kidney disease and nephrocalcinosis. This indicates that all survivors of IH should be closely monitored, with early implementation of preventive measures, e.g. inhibition of active metabolites of vitamin D3 synthesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfaa178DOI Listing
October 2020

Cardiovascular Risk Assessment in Children With Chronic Cholestatic Liver Diseases.

J Pediatr Gastroenterol Nutr 2020 11;71(5):647-654

Department of Gastroenterology, Hepatology, Nutritional Disorders and Pediatrics.

Objectives: Chronic cholestatic liver diseases are often associated with disturbed lipid metabolism, which may potentially increase cardiovascular (CV) risk but the evidence is scarce. The aim of the study was to assess factors associated with increased CV risk in children with Alagille syndrome (AGS) and biliary atresia (BA).

Methods: We investigated 17 patients with AGS, ages 11.0 years (8.4-13.4) and 19 with BA, ages 13.5 years (10.4-15.1) in whom we performed thorough biochemical assessment including lipid profiles and oxidative stress biomarkers, blood pressure (BP)-systolic, diastolic and mean, carotid intima-media thickness (cIMT), and pulse wave velocity (PWV).

Results: There were abnormal lipid profiles in 82% of children with AGS and 52.6% with BA. In AGS group, we observed significantly higher levels of TC, LDL C, APO B, lower glutathione concentration and glutathione peroxidase activity and lower blood pressure, lower cIMT (P = 0.02), cIMT-SDS (P = 0.04), and PWV (P = 0.04). We, however, observed elevated blood pressure in 2/19 patients with BA and none-with AGS (BA vs AGS: P = 0.12), whereas cIMT-SDS was increased only in 2/17 patients with AGS and in 6/19 with BA (P = 0.24), and abnormal PWV-SDS values were detected in 3/17 of AGS and 8/19 of BA patients (P = 0.15). Neither presence of dyslipidemia nor Lp-X correlated with vascular parameters.

Conclusions: Children with BA and AGS may present with increased cardiovascular risk factors but vascular parameters are not directly related to lipid abnormalities. cIMT and BP should be considered for clinical practice in these cholestatic disorders so as to determine individuals with potential CV risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MPG.0000000000002874DOI Listing
November 2020

Origins of Primary Hypertension in Children: Early Vascular or Biological Aging?

Hypertension 2020 Nov 28;76(5):1400-1409. Epub 2020 Sep 28.

Division of Nephrology, Department of Pediatrics (J.F.), The Children's Memorial Health Institute, Warsaw, Poland.

Although relatively rare in childhood, primary hypertension (PH) is thought to have originated in childhood and may be even determined perinatally. PH prevalence increases in school-age children and affects 11% of 18-year-old adolescents. Associated with metabolic risk factors, elevated blood pressure in childhood is carried into adulthood. Analysis of the phenotype of hypertensive children has revealed that PH is a complex of anthropometric and neuro-immuno-metabolic abnormalities, typically found in hypertensive adults. Children with elevated blood pressure have shown signs of accelerated biological development, which are closely associated with further development of PH, metabolic syndrome, and cardiovascular disease in adulthood. At the time of diagnosis, hypertensive children were reported to have significant arterial remodelling expressed as significantly increased carotid intima-media thickness, increased stiffness of large arteries, lower area of microcirculation, and decreased endothelial function. These changes indicate that their biological age is 4 to 5 years older than their normotensive peers. All these abnormalities are typical features of early vascular aging described in adults with PH. However, as these early vascular changes in hypertensive children are closely associated with features of accelerated biological development and neuro-immuno-metabolic abnormalities observed in older subjects, it seems that PH in childhood is not only an early vascular aging event, but also an early biological maturation phenomenon.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14586DOI Listing
November 2020

Evolution of isolated systolic hypertension with normal central blood pressure in adolescents-prospective study.

Pediatr Nephrol 2021 Feb 3;36(2):361-371. Epub 2020 Sep 3.

Department of Nephrology, Kidney Transplantation and Hypertension, The Children's Memorial Health Institute, Aleja Dzieci Polskich 20, 04-730, Warsaw, Poland.

Background: The clinical significance of isolated systolic hypertension with normal central blood pressure known as spurious hypertension (sHT) in adolescents and its evolution over time is not known.

Methods: The aim of this study was to analyze changes in office, ambulatory blood pressure (ABPM), central systolic blood pressure (cSBP), hemodynamic parameters, and target organ damage (TOD) over a 1-year follow-up in a group of non-obese children with sHT.

Results: Of 294 patients referred for primary hypertension, 138 patients (31 girls; 22%) had hypertension confirmed by ABPM. 48/138 (35%) patients (7 girls; 15%) were diagnosed with sHT (elevated office and ambulatory systolic BP, but normal cSBP); 43 of them (6 girls; 14%) were followed for 12 ± 3 months during non-pharmacological therapy. At baseline 7 (16%) patients had borderline values of cIMT or LVMi indicating mild TOD. After 12 months, 10/43 (3 girls; 23%) patients developed sustained HT (elevated office, ambulatory BP and cSBP), 11/43 (1 girl; 26%) maintained sHT, and 22/43 (2 girls; 51%) evolved to white coat hypertension or normotension. The cSBP values increased in 27 patients (4 girls; 63%), but the group average remained in the normal range. Prevalence of TOD did not change during observation. The multivariate regression analysis showed that the only predictor of cSBP change over time was a change in serum uric acid level.

Conclusions: In conclusion, after 1 year of non-pharmacological treatment, 23% of adolescents with sHT developed sustained hypertension, with the main predictor of cSBP change being the change in serum uric acid.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-020-04731-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815547PMC
February 2021

It Is Time for Microcirculation.

Hypertension 2020 Aug 8;76(2):327-329. Epub 2020 Jul 8.

From the Department of Nephrology and Arterial Hypertension, The Children's Memorial Health Institute, Warsaw, Poland.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15471DOI Listing
August 2020

Prevalence of arterial hypertension, hemodynamic phenotypes, and left ventricular hypertrophy in children after coarctation repair: a multicenter cross-sectional study.

Pediatr Nephrol 2020 11 11;35(11):2147-2155. Epub 2020 Jun 11.

Department of Nephrology and Arterial Hypertension, The Children's Memorial Health Institute, Warsaw, Poland.

Background: This study aimed to evaluate hemodynamic phenotypes and prevalence of left ventricular hypertrophy in children after coarctation repair with right arm and leg blood pressure difference < 20 mmHg. Secondary objectives were analysis of effects of age at intervention, residual gradient across the descending aorta, and type of correction.

Methods: Blood pressure status and left ventricular hypertrophy were diagnosed according to European Society of Hypertension 2016 guidelines.

Results: Of 90 patients with a median age 12.5 (8.9-15.8) years, 8.5 (6.0-11.8) years after coarctation repair who were included, 42 (46.7%) were hypertensive. Isolated systolic hypertension dominated among 29 hypertensive patients with uncontrolled or masked hypertension (25 of 29; 86.2%). Of the 48 patients with office normotension, 14.6% (7) had masked hypertension, 8.3% (4) had ambulatory prehypertension, and 54.2% (26) were truly normotensive. Left ventricular hypertrophy was diagnosed in 29 patients (32.2%), including 14 of 42 (33.3%) hypertensive and 15 of 48 (31.3%) normotensive patients. The peak systolic gradient across the descending aorta was greater in hypertensive subjects (33.3 ± 12.7 mmHg) compared with normotensive subjects (25 ± 8.2 mmHg, p = 0.0008). Surgical correction was performed earlier than percutaneous intervention (p < 0.0001) and dominated in 40 of 48 (83.3%) normotensive versus 24 of 42 (57.1%) hypertensive patients (p = 0.006).

Conclusions: Arterial hypertension with isolated systolic hypertension as the dominant phenotype and left ventricular hypertrophy are prevalent even after successful coarctation repair. Coarctation correction from the age of 9 years and older was associated with a higher prevalence of hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-020-04645-wDOI Listing
November 2020

Use of Static Cutoffs of Hypertension to Determine High cIMT in Children and Adolescents: An International Collaboration Study.

Can J Cardiol 2020 Sep 4;36(9):1467-1473. Epub 2020 Mar 4.

Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China. Electronic address:

Background: Pediatric hypertension is typically defined as blood pressure ≥ sex-, age-, and height-specific 95th percentile (high) cutoffs. Given the number of strata, there are hundreds of cutoffs for defining elevated and high blood pressure that make it cumbersome to use in clinical practice. This study aimed to evaluate the utility of the static cutoffs for pediatric hypertension (120/80 mm Hg for children and 130/80 mm Hg for adolescents) in determining high carotid intimamedia thickness (cIMT) in children and adolescents.

Methods: Data were from 6 population-based cross-sectional studies in Brazil, China, Greece, Italy, Spain, and the United Kingdom. A total of 4280 children and adolescents, aged 6 to 17 years, were included. High cIMT was defined as cIMT ≥ sex-, age- and cohort-specific 90th percentile cutoffs.

Results: Compared with normal blood pressure, hypertension defined using the percentile-based cutoffs from 2017 American Academy of Pediatrics guideline, and the static cutoffs were associated with similar higher odds for high cIMT (percentile-based cutoffs: odds ratio [OR], 1.46, 95% confidence interval [CI], 1.15-1.86; static cutoffs: OR, 1.65, 95% CI, 1.25-2.17), after adjustment for sex, age, race/ethnicity, body mass index, high-density lipoprotein-cholesterol, triglyceride, and fasting blood glucose. The similar utility of 2 definitions in determining high cIMT was further confirmed by area under the receiver operating characteristic curve and net reclassification improvement methods (P for difference > 0.05).

Conclusion: Static cutoffs (120/80 mm Hg for children, 130/80 mm Hg for adolescents) performed similarly compared with percentile-based cutoffs in determining high cIMT, supporting the use of static cutoffs in identifying pediatric hypertension in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cjca.2020.02.093DOI Listing
September 2020

Obesity, metabolic syndrome, and primary hypertension.

Pediatr Nephrol 2021 Apr 9;36(4):825-837. Epub 2020 May 9.

Department of Public Health, The Children's Memorial Health Institute, Warsaw, Poland.

Primary hypertension is the dominant form of arterial hypertension in adolescents. Disturbed body composition with, among other things, increased visceral fat deposition, accelerated biological maturation, metabolic abnormalities typical for metabolic syndrome, and increased adrenergic drive constitutes the intermediary phenotype of primary hypertension. Metabolic syndrome is observed in 15-20% of adolescents with primary hypertension. These features are also typical of obesity-related hypertension. Metabolic abnormalities and metabolic syndrome are closely associated with both the severity of hypertension and the risk of target organ damage. However, even though increased body mass index is the main determinant of blood pressure in the general population, not every hypertensive adolescent is obese and not every obese patient suffers from hypertension or metabolic abnormalities typical for metabolic syndrome. Thus, the concepts of metabolically healthy obesity, normal weight metabolically unhealthy, and metabolically unhealthy obese phenotypes have been developed. The risk of hypertension and hypertensive target organ damage increases with exposure to metabolic risk factors which are determined by disturbed body composition and visceral obesity. Due to the fact that both primary hypertension and obesity-related hypertension present similar pathogenesis, the principles of treatment are the same and are focused not only on lowering blood pressure, but also on normalizing body composition and metabolic abnormalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-020-04579-3DOI Listing
April 2021

Systematic and Multidisciplinary Evaluation of Fibromuscular Dysplasia Patients Reveals High Prevalence of Previously Undetected Fibromuscular Dysplasia Lesions and Affects Clinical Decisions: The ARCADIA-POL Study.

Hypertension 2020 Apr 9;75(4):1102-1109. Epub 2020 Mar 9.

From the Departments of Hypertension (E.W.-C., A.P., P.D., E.F., K.J.-P., M.K., M.P., K.H., P.T., M.S., K.K., A.J.), Institute of Cardiology, Warsaw, Poland.

Fibromuscular dysplasia (FMD), regarded as a generalized vascular disease, may affect all vascular beds and may result in arterial stenosis, occlusion, aneurysm, or dissection. It has been proposed to systematically evaluate all vascular beds in patients with FMD, regardless of initial FMD involvement. However, the impact of this approach on clinical decisions and on management is unknown. Within the prospective ARCADIA-POL study (Assessment of Renal and Cervical Artery Dysplasia-Poland), we evaluated 232 patients with FMD lesions confirmed in at least one vascular bed, out of 343 patients included in the registry. All patients underwent a detailed clinical evaluation including computed tomography angiography of intracranial and cervical arteries, as well as computed tomography angiography of the abdominal aorta, its branches, and upper and lower extremity arteries. In the study group, FMD lesions were most frequently found in renal arteries (87.5%). FMD was also found in cerebrovascular (24.6%), mesenteric (13.8%), and upper (3.0%) and lower extremity (9.9 %) arteries. Newly diagnosed FMD lesions were found in 34.1% of the patients, and previously undetected vascular complications were found in 25% of the patients. Among all FMD patients included in the study, one out of every 4 evaluated patients qualified for interventional treatment due to newly diagnosed FMD lesions or vascular complications. The ARCADIA-POL study shows for the first time that the systematic and multidisciplinary evaluation of patients with FMD based on a whole-body computed tomography angiography scan has an impact on their clinical management. This proved the necessity of the systematic evaluation of all vascular beds in patients with FMD, regardless of initial FMD involvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13239DOI Listing
April 2020

Dissecting visceral fibromuscular dysplasia reveals a new vascular phenotype of the disease: a report from the ARCADIA-POL study.

J Hypertens 2020 04;38(4):737-744

Department of Hypertension, Institute of Cardiology, Warsaw.

Objective: Visceral artery fibromuscular dysplasia (VA FMD) manifestations range from asymptomatic to life-threatening. The aim of the study is to evaluate the prevalence and clinical characteristics of VA FMD.

Methods: A total of 232 FMD patients enrolled into ongoing ARCADIA-POL study were included in this analysis. All patients underwent detailed clinical evaluation including ambulatory blood pressure monitoring, biobanking, duplex Doppler of carotid and abdominal arteries and whole body angio-computed tomography. Three control groups (patients with renal FMD without visceral involvement, healthy normotensive patients and resistant hypertensive patients) matched for age and sex were included.

Results: VA FMD was present in 32 patients (13.8%). Among these patients (women: 84.4%), FMD lesions were more frequent in celiac trunk (83.1%), 62.5% of patients showed at least one visceral aneurysm, and five patients presented with severe complications related to VA FMD. No demographic differences were found between patients with VA FMD and individuals from the three control groups, with the exception of lower weight (P < 0.001) and BMI (P < 0.001) in VA FMD patients. Patients with FMD (with or without visceral artery involvement) showed significantly smaller visceral arterial diameters compared with controls without FMD.

Conclusion: Patients with FMD showed smaller visceral arterial diameters when compared with patients without FMD. This may reflect a new phenotype of FMD, as a generalized arteriopathy, what needs further investigation. Lower BMI in patients with VA FMD might be explained by chronic mesenteric ischemia resulting from FMD lesions. FMD visceral involvement and visceral arterial aneurysms in patients with renal FMD are far to be rare. This strengthens the need for a systematic evaluation of all vascular beds, including visceral arteries, regardless of initial FMD involvement.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002327DOI Listing
April 2020

Hemodynamic Patterns and Target Organ Damage in Adolescents With Ambulatory Prehypertension.

Hypertension 2020 03 30;75(3):826-834. Epub 2019 Dec 30.

From the Department of Nephrology, Kidney Transplantation and Hypertension (L.O., M.L.), The Children's Memorial Health Institute, Warsaw, Poland.

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 (<0.05). Central systolic BP was higher in patients with AmbPreHT, AmbHT, and SevAmbHT compared with normotensives (<0.01). In all 3 groups, the carotid intima-media thickness scores were significantly higher than in normotensive (<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 (<0.001). Pulse wave velocity scores were increased in patients with AmbPreHT, AmbHT, and SevAmbHT compared with patients with normotension (<0.01). Multiple regression analysis showed that body mass index 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14149DOI Listing
March 2020

Regulatory T-cell subset distribution in children with primary hypertension is associated with hypertension severity and hypertensive target organ damage.

J Hypertens 2020 04;38(4):692-700

Department of Nephrology, Kidney Transplantation and Arterial Hypertension.

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 (CD4CD25CD127) and their subsets (CD45RA-naive Tregs, CD45RA memory/activated Tregs, CD45RACD31 recent thymic emigrants Tregs and mature naive CD45RACD31 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 CD45RACD31 Tregs. Decreased frequency of the total Tregs, naive Tregs and CD31-bearing Treg cell subsets (CD31 total Tregs, CD45RACD31 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002328DOI Listing
April 2020

Metabolic syndrome, clustering of cardiovascular risk factors and high carotid intima-media thickness in children and adolescents.

J Hypertens 2020 04;38(4):618-624

Department of Epidemiology, School of Public Health, Shandong University, Jinan, China.

Objective: The clinical utility of screening for pediatric metabolic syndrome (MetS) in children and adolescents is still controversial. We examined the performance of pediatric MetS vs. clustering of cardiovascular risk factors (which are the components of MetS) for predicting high carotid intima-media thickness (cIMT) in children and adolescents.

Methods: Participants included 2427 children and adolescents aged 6-17 years from population-based studies in three countries (Brazil, China and Italy). Pediatric MetS was defined using either the modified National Cholesterol Education Program Adult Treatment Panel III criteria or the modified International Diabetes Federation criteria. Clustering of cardiovascular risk factors was calculated as the sum of five components of MetS (i.e. central obesity, elevated blood pressure, elevated triglycerides, reduced HDL-cholesterol and elevated fasting blood glucose). High cIMT was defined as cIMT at least 95th percentile values for sex and age developed from European children.

Results: Presence of one, two or at least three cardiovascular risk factors (using the National Cholesterol Education Program Adult Treatment Panel III criteria), as compared with none, was associated with gradually increasing odds of high cIMT [odds ratios (95% confidence intervals): 1.60 (1.29-1.99), 2.89 (2.21-3.78) and 4.24 (2.81-6.39), respectively]. High cIMT was also associated with presence (vs. absence) of MetS (odds ratio = 2.88, 95% confidence interval = 1.95-4.26). However, clustering of cardiovascular risk factors predicted high cIMT markedly better than MetS (area under the curve of 0.66 vs. 0.54, respectively). Findings were similar using the International Diabetes Federation criteria for pediatric MetS.

Conclusion: In children and adolescents, a graded score based on five cardiovascular risk factors (used to define MetS) predicted high cIMT markedly better than MetS. These findings do not support the clinical utility of MetS for screening youth at increased cardiovascular risk, as expressed in this study by high cIMT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000002318DOI Listing
April 2020

International Waist Circumference Percentile Cutoffs for Central Obesity in Children and Adolescents Aged 6 to 18 Years.

J Clin Endocrinol Metab 2020 04;105(4)

Department of Epidemiology and Health Services, Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland.

Context: No universal waist circumference (WC) percentile cutoffs used have been proposed for screening central obesity in children and adolescents.

Objective: To develop international WC percentile cutoffs for children and adolescents with normal weight based on data from 8 countries in different global regions and to examine the relation with cardiovascular risk.

Design And Setting: We used pooled data on WC in 113,453 children and adolescents (males 50.2%) aged 4 to 20 years from 8 countries in different regions (Bulgaria, China, Iran, Korea, Malaysia, Poland, Seychelles, and Switzerland). We calculated WC percentile cutoffs in samples including or excluding children with obesity, overweight, or underweight. WC percentiles were generated using the general additive model for location, scale, and shape (GAMLSS). We also estimated the predictive power of the WC 90th percentile cutoffs to predict cardiovascular risk using receiver operator characteristics curve analysis based on data from 3 countries that had available data (China, Iran, and Korea). We also examined which WC percentiles linked with WC cutoffs for central obesity in adults (at age of 18 years).

Main Outcome Measure: WC measured based on recommendation by the World Health Organization.

Results: We validated the performance of the age- and sex-specific 90th percentile WC cutoffs calculated in children and adolescents (6-18 years of age) with normal weight (excluding youth with obesity, overweight, or underweight) by linking the percentile with cardiovascular risk (area under the curve [AUC]: 0.69 for boys; 0.63 for girls). In addition, WC percentile among normal weight children linked relatively well with established WC cutoffs for central obesity in adults (eg, AUC in US adolescents: 0.71 for boys; 0.68 for girls).

Conclusion: The international WC cutoffs developed in this study could be useful to screen central obesity in children and adolescents aged 6 to 18 years and allow direct comparison of WC distributions between populations and over time.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgz195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059990PMC
April 2020

Haemodiafiltration does not lower protein-bound uraemic toxin levels compared with haemodialysis in a paediatric population.

Nephrol Dial Transplant 2020 04;35(4):648-656

Department of Internal Medicine & Pediatrics, Ghent University, Ghent, Belgium.

Background: Haemodiafiltration (HDF) is accepted to effectively lower plasma levels of middle molecules in the long term, while data are conflicting with respect to the additive effect of convection on lowering protein-bound uraemic toxins (PBUTs). Here we compared pre-dialysis β2-microglobulin (β2M) and PBUT levels and the percentage of protein binding (%PB) in children on post-dilution HDF versus conventional high- (hf) or low-flux (lf) haemodialysis (HD) over 12 months of treatment.

Methods: In a prospective multicentre, non-randomized parallel-arm intervention study, pre-dialysis levels of six PBUTs and β2M were measured in children (5-20 years) on post-HDF (n = 37), hf-HD (n = 42) and lf-HD (n = 18) at baseline and after 12 months. Analysis of variance was used to compare levels and %PB in post-HDF versus conventional hf-HD and lf-HD cross-sectionally at 12 months and longitudinal from baseline to 12 months.

Results: For none of the PBUTs, no difference was found in either total and free plasma levels or %PB between post-HDF versus the hf-HD and lf-HD groups. Children treated with post-HDF had lower pre-dialysis β2M levels [median 23.2 (21.5; 26.6) mg/dL] after 12 months versus children on hf-HD [P<0.01; 35.2 (29.3; 41.2) mg/dL] and children on lf-HD [P<0.001; 47.2 (34.3; 53.0) mg/dL]. While β2M levels remained steady in the hf-HD and lf-HD group, a decrease in β2M was demonstrated for children on post-HDF (P<0.01).

Conclusions: While post-HDF successfully decreased β2M, no additive effect on PBUT over 12 months of treatment was found. PBUT removal is complex and hampered by several factors. In children, these factors might be different from adults and should be explored in future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfz132DOI Listing
April 2020

Association of intrarenal blood flow with renal function and target organ damage in hypertensive patients with fibromuscular dysplasia: the ARCADIA-POL study.

Pol Arch Intern Med 2019 04 7;129(4):234-241. Epub 2019 Mar 7.

Department of Hypertension, Institute of Cardiology, Warsaw, Poland

INTRODUCTION Data on the assessment of intrarenal blood flow parameters in patients with renal fibromuscular dysplasia (FMD) are scarce. OBJECTIVES The aim of the study was to evaluate intrarenal blood flow parameters in patients with FMD and significant or nonsignificant renal artery stenosis (RAS). PATIENTS AND METHODS We evaluated intrarenal blood flow parameters by Doppler ultrasonography in 153 patients with renal FMD enrolled in the ARCADIA‑POL study: 32 and 121 patients with and without significant RAS, respectively, compared with 60 matched patients with essential hypertension and 60 healthy controls. RESULTS Patients with FMD and significant RAS had a lower renal resistive index (RRI) compared with patients with FMD without significant RAS, patients with essential hypertension, and normotensive controls (mean [SD], 0.51 [0.08] vs 0.60 [0.07], 0.62 [0.06], and 0.61 [0.06], respectively; P <0.001). In patients with nonsignificant RAS, RRI correlated significantly with carotid intima-media thickness, 24‑hour diastolic blood pressure, 24‑hour pulse pressure, left ventricular diastolic function, known duration time of hypertension, and age. In patients with significant RAS, there was a significant correlation between RRI and known duration time of hypertension, left ventricular diastolic function, and age. In a separate, "per‑kidney" analysis, renal arteries with FMD and significant RAS were characterized by lower RRI values, higher maximal blood flow velocity, higher renal aortic ratio, and longer acceleration time compared with renal arteries with FMD and nonsignificant RAS as well as renal arteries without FMD. CONCLUSIONS In contrast to atherosclerotic RAS, intrarenal blood flow in patients with FMD and RAS is preserved, confirming that renal vasculature is relatively intact in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20452/pamw.4479DOI Listing
April 2019

Uremic Toxin Concentrations are Related to Residual Kidney Function in the Pediatric Hemodialysis Population.

Toxins (Basel) 2019 04 24;11(4). Epub 2019 Apr 24.

Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.

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 ( = 170) by comparing these with healthy and non-dialysis chronic kidney disease (CKD) stage 4-5 ( = 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 (). 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 ( -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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/toxins11040235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521157PMC
April 2019

Leukocyte matrix metalloproteinase and tissue inhibitor gene expression patterns in children with primary hypertension.

J Hum Hypertens 2020 05 29;34(5):355-363. Epub 2019 Mar 29.

Department of Nephrology and Arterial Hypertension, The Children's Memorial Health Institute, Warsaw, Poland.

Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play an important role in cardiovascular remodeling. The aim of the study was to analyze MMP/TIMP genes expression in peripheral blood leukocytes of 80 hypertensive children (15.1 ± 2.0 years) in comparison with age-matched 78 normotensive children (14.6 ± 2.0 years; n.s.). TIMP and MMP expression in peripheral blood leukocytes was assessed by quantitative real-time PCR. Hypertensive children independently of age, sex, and body mass index had greater expression of MMP-2 than normotensive controls (p = 0.0001). Patients with left ventricular hypertrophy had greater expression of MMP-14 than patients with normal left ventricular mass (p = 0.006) and TIMP-2 expression correlated with carotid wall cross-sectional area (p = 0.03; r = 0.238). MMP-14 expression correlated with BMI-SDS (p = 0.001; r = 0.371), waist circumference-SDS (p = 0.016; r = 0.290), hsCRP (p = 0.003; r = 0.350), serum HDL-cholesterol (p = 0.008; r = -0.304), and serum uric acid (p = 0.0001; r = 0.394). In conclusion, hypertensive adolescents presented significant alterations of MMP/TIMP expression pattern in comparison with normotensive peers. Moreover, altered MMP/TIMP expression was associated with hypertensive target organ damage and metabolic abnormalities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41371-019-0197-8DOI Listing
May 2020

Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study.

J Am Soc Nephrol 2019 04 7;30(4):678-691. Epub 2019 Mar 7.

Nephrology Unit, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.

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 2-microglobulin. The HDF cohort had lower 2-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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2018100990DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442347PMC
April 2019

Height-specific blood pressure cutoffs for screening elevated and high blood pressure in children and adolescents: an International Study.

Hypertens Res 2019 06 26;42(6):845-851. Epub 2018 Dec 26.

Department of Epidemiology, School of Public Health, Shandong University, Jinan, China.

Pediatric blood pressure (BP) reference tables are generally based on sex, age, and height and tend to be cumbersome to use in routine clinical practice. In this study, we aimed to develop a new, height-specific simple BP table according to the international child BP reference table based on sex, age and height and to evaluate its performance using international data. We validated the simple table in a derivation cohort that included 58,899 children and adolescents aged 6-17 years from surveys in 7 countries (China, India, Iran, Korea, Poland, Tunisia, and the United States) and in a validation cohort that included 70,072 participants from three other surveys (China, Poland and Seychelles). The BP cutoff values for the simple table were calculated for eight height categories for both the 90th ("elevated BP") and 95th ("high BP") percentiles of BP. The simple table had a high performance to predict high BP compared to the reference table, with high values (boys/girls) of area under the curve (0.94/0.91), sensitivity (88.5%/82.9%), specificity (99.3%/99.7%), positive predictive values (93.9%/97.3%), and negative predictive values (98.5%/97.8%) in the pooled data from 10 studies. The simple table performed similarly well for predicting elevated BP. A simple table based on height only predicts elevated BP and high BP in children and adolescents nearly as well as the international table based on sex, age, and height. This has important implications for simplifying the detection of pediatric high BP in clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41440-018-0178-2DOI Listing
June 2019

A 21-year-old woman with neurofibromatosis type 1, mid-aortic syndrome, and hypertension.

Pol Arch Intern Med 2019 02 13;129(2):131-132. Epub 2018 Dec 13.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.20452/pamw.4393DOI Listing
February 2019

Bacterial Microbiota and Fatty Acids in the Faeces of Overweight and Obese Children.

Pol J Microbiol 2018;67(3):339-345

Institute of Chemistry, Environmental Protection and Biotechnology, Jan Długosz University in Częstochowa, Częstochowa, Poland.

The growing number of children with overweight and obesity constitutes a major health problem of the modern world and it has been suggested that intestinal microbiota may influence energy intake from food. The objectives of this study were to determine quantity and proportions of dominant genera of Bacteroides, Prevotella (phylum Bacteroidetes ); Clostridium , Lactobacillus (phylum Firmicutes ) and Bifidobacterium (phylum Actinobacteria ) in the intestines and to determine the content of short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) in the stool of 20 obese children and 20 children with normal body weight. Strains classified as Firmicutes ( Clostridium and Lactobacillus ) predominated in stool microbiota of obese children, while those of Bacteroidetes ( Prevotella and Bacteroides ) were in minority ( p < 0.001). Concentration of SCFAs in the stool of obese children was lower in comparison to the stool of normal weight children ( p = 0.04). However, these differences were significant only in obese children, not in overweight children in comparison with the lean ones. Therefore, in our study obesity was associated with intestinal dysbiosis and a predominance of phylum Firmicutes . Secondly, stool of obese children contained lower amounts of SCFAs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21307/pjm-2018-041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256813PMC
June 2019

Central systolic blood pressure and central pulse pressure predict left ventricular hypertrophy in hypertensive children.

Pediatr Nephrol 2019 04 13;34(4):703-712. Epub 2018 Nov 13.

Department of Public Health, The Children's Memorial Health Institute, Warsaw, Poland.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-018-4136-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394668PMC
April 2019

Effect of haemodiafiltration vs conventional haemodialysis on growth and cardiovascular outcomes in children - the HDF, heart and height (3H) study.

BMC Nephrol 2018 08 10;19(1):199. Epub 2018 Aug 10.

Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany.

Background: Cardiovascular disease is prevalent in children on dialysis and accounts for almost 30% of all deaths. Randomised trials in adults suggest that haemodiafiltration (HDF) with high convection volumes is associated with reduced cardiovascular mortality compared to high-flux haemodialysis (HD); however paediatric data are scarce. We designed the haemodiafiltration, heart and height (3H) study to test the hypothesis that children on HDF have an improved cardiovascular risk profile, growth and nutritional status and quality of life, compared to those on conventional HD. We performed a non-randomised parallel-arm intervention study within the International Paediatric Haemodialysis Network Registry comparing children on HDF and conventional HD to determine annualised change in cardiovascular end-points and growth. Here we present the 3H study design and baseline characteristics of the study population.

Methods: 190 children were screened and 177 (106 on HD and 71 on HDF) recruited from 28 centres in 10 countries. There was no difference in age, underlying diagnosis, comorbidities, previous dialysis therapy, dialysis vintage, residual renal function, type of vascular access or blood flow between HD and HDF groups. High flux dialysers were used in 63% of HD patients and ultra-pure water was available in 52%. HDF patients achieved a median convection volume of 13.3 L/m; this was associated with the blood flow rate only ((p = 0.0004, r = 0.42) and independent of access type (p = 0.38).

Discussion: This is the largest study on dialysis outcomes in children that involves deep phenotyping across a wide range of cardiovascular, anthropometric, nutritional and health-related quality of life measures, to test the hypothesis that HDF leads to improved cardiovascular and growth outcomes compared to conventional HD.

Trial Registration: ClinicalTrials.gov: NCT02063776 . The trial was prospectively registered on the 14 Feb 2014.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12882-018-0998-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086045PMC
August 2018

Loss of CD31 receptor in CD4+ and CD8+ T-cell subsets in children with primary hypertension is associated with hypertension severity and hypertensive target organ damage.

J Hypertens 2018 11;36(11):2148-2156

Department of Nephrology, Kidney Transplantation and Arterial Hypertension.

Background: Primary hypertension is associated with still poorly known T-cell dependent immunity defects that participate in the disease development. However, the relationship between peripheral T-cell subset distribution and disease severity in humans is not known. The aim of the study was to find out if target organ damage in adolescents with primary hypertension is associated with thymus-dependent lymphocytes renewal reflected by changes in the T-cell subset phenotype characteristics.

Methods: Using seven-color flow cytometry technique, we assessed CD31, CCR7 and CD28 receptors expression in CD45RA and CD45RO bearing peripheral CD4 and CD8 T-cell subsets. The study included 32 hypertensive children/adolescents and 35 sex-matched and age-matched controls.

Results: Children with primary hypertension had slightly increased CD4 T-cell pool but decreased population of CD31 expressing CD4 T-cell subsets (recent thymic emigrants). Frequency of the CD4 and CD4/CD45RA+ T cells lacking CD31 correlated positively with the hypertensive organ damage markers (pulse wave velocity, central blood pressure, left ventricular mass index). Left ventricular hypertrophy was associated with decreased CD4/CD45RA:CD4/CD45RO ratio, loss of the CD31 receptor in the CD4 and CD8 T-cell subsets and increased population of effector/memory T cells bearing CD8/CD28 and CD8/CD45RA+/CCR7 phenotype. Regression analysis revealed that these associations were independent of age, sex, and BMI.

Conclusion: The results suggest that subclinical arterial injury and left ventricular hypertrophy in adolescents with primary hypertension is associated with declined thymic function and increased pool of T cells bearing effector/memory phenotype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/HJH.0000000000001811DOI Listing
November 2018

Risk Factors for Early Dialysis Dependency in Autosomal Recessive Polycystic Kidney Disease.

J Pediatr 2018 08 9;199:22-28.e6. Epub 2018 May 9.

Department of Pediatrics, University Hospital of Cologne, Cologne, Germany; Center for Molecular Medicine, University Hospital of Cologne, Cologne, Germany.

Objective: To identify prenatal, perinatal, and postnatal risk factors for dialysis within the first year of life in children with autosomal recessive polycystic kidney disease (ARPKD) as a basis for parental counseling after prenatal and perinatal diagnosis.

Study Design: A dataset comprising 385 patients from the ARegPKD international registry study was analyzed for potential risk markers for dialysis during the first year of life.

Results: Thirty-six out of 385 children (9.4%) commenced dialysis in the first year of life. According to multivariable Cox regression analysis, the presence of oligohydramnios or anhydramnios, prenatal kidney enlargement, a low Apgar score, and the need for postnatal breathing support were independently associated with an increased hazard ratio for requiring dialysis within the first year of life. The increased risk associated with Apgar score and perinatal assisted breathing was time-dependent and vanished after 5 and 8 months of life, respectively. The predicted probabilities for early dialysis varied from 1.5% (95% CI, 0.5%-4.1%) for patients with ARPKD with no prenatal sonographic abnormalities to 32.3% (95% CI, 22.2%-44.5%) in cases of documented oligohydramnios or anhydramnios, renal cysts, and enlarged kidneys.

Conclusions: This study, which identified risk factors associated with onset of dialysis in ARPKD in the first year of life, may be helpful in prenatal parental counseling in cases of suspected ARPKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpeds.2018.03.052DOI Listing
August 2018