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.

Naturally occurring stable calcium isotope ratios are a novel biomarker of bone calcium balance in chronic kidney disease.

Dysregulated calcium homeostasis is common in chronic kidney disease and causally associated with disorders of bone mineralization. However, radiological measures and biomarkers do not allow accurate evaluation of bone calcium balance. Non-radioactive calcium isotopes, 42Ca and 44Ca, are present in our diet and sequestered into body compartments following principles of kinetic isotope fractionation. Isotopically light 42Ca is preferentially incorporated into bone, while heavier 44Ca is excreted. The ratio (44/42Caserum) increases when bone formation exceeds resorption and vice versa, reflecting bone calcium balance. We measured these calcium isotopes by inductively coupled plasma mass-spectrometry in blood, urine and feces of 42 children with chronic kidney disease and 92 receiving dialysis therapy. We compared the isotope ratios with bone biomarkers and determined total bone mineral content by dual-energy x-ray absorptiometry and peripheral quantitative CT expressed as age-adjusted z-scores. The 44/42Caserum ratio positively correlated with serum calcium, 25-hydroxyvitamin D and alkaline phosphatases and inversely with serum parathyroid hormone and other bone resorption markers. The 44/42Caserum ratio positively correlated with age-adjusted z-scores of tibial trabecular bone mineral density and total bone mineral content measured by peripheral quantitative CT, and hip bone mineral density measured by dual-energy X-ray absorptiometry. Significant and independent predictors of total bone mineral content, measured by, were the 44/42Caserum ratio and parathyroid hormone. The 44/42Caserum ratio, repeated after four weeks, highly correlated with baseline values. When adjusted for calcium-containing medications and kidney impairment, the 44/42Caserum ratio in patients receiving dialysis was 157% lower than that of age-matched children and 29% lower than levels in elderly women with osteoporosis, implying significantly lower bone mineral content. Thus, calcium isotope ratios may provide a novel, sensitive and non-invasive method of assessing bone calcium balance in chronic kidney disease.

The immunopathogenesis of idiopathic nephrotic syndrome: a narrative review of the literature.

Idiopathic nephrotic syndrome (INS) is a common glomerular disease in childhood, and the immunological involvement in the pathogenesis of non-genetic INS, although not fully elucidated, is evident. This narrative review aims to offer a concise and in-depth view of the current knowledge on the immunological mechanisms of the development of INS as well as the role of the immunological components of the disease in the responsiveness to treatment. T cell immunity appears to play a major role in the INS immunopathogenesis and has been the first to be linked to the disease. Various T cell immunophenotypes are implicated in INS, including T-helper-1, T-helper-2, T-helper-17, and T regulatory cells, and various cytokines have been proposed as surrogate biomarkers of the disease; however, no distinct T helper or cytokine profile has been conclusively linked to the disease. More recently, the recognition of the role of B cell mediated immunity and the various B cell subsets that are dysregulated in patients with INS have led to new hypotheses on the underlying immunological causes of INS. Finally, the disambiguation of the exact mechanisms of the INS development in the future may be the key to the development of more targeted personalized approaches in managing INS. CONCLUSIONS: INS demonstrates particularly interesting immunopathogenetic pathways, in which multiple interactions between T cell and B cell immunity and the podocyte are involved. The disambiguation of these pathways will provide promising novel therapeutic targets in INS. WHAT IS KNOWN: • INS is the most common glomerular disease in the paediatric population, and its onset and relapses have been linked to various immunological triggers. • Multiple immunological mechanisms have been implicated in the pathogenesis of INS; however, no single distinct immunological profile has been recognized. WHAT IS NEW: • Th17 cells and Treg cells play an important role in the immune dysregulation in INS. • Transitional B cell levels as well as the transitional/memory B cell ratio have been correlated to nephrotic relapses and have been proposed as biomarkers of INS relapses in SSNS patients.

Routine serum biomarkers, but not dual-energy X-ray absorptiometry, correlate with cortical bone mineral density in children and young adults with chronic kidney disease.

BACKGROUND: Biomarkers and dual-energy X-ray absorptiometry (DXA) are thought to be poor predictors of bone mineral density (BMD). The Kidney Disease: Improving Global Outcomes guidelines suggest using DXA if the results will affect patient management, but this has not been studied in children or young adults in whom bone mineral accretion continues to 30 years of age. We studied the clinical utility of DXA and serum biomarkers against tibial cortical BMD (CortBMD) measured by peripheral quantitative computed tomography, expressed as Z-score CortBMD, which predicts fracture risk. METHODS: This was a cross-sectional multicentre study in 26 patients with CKD4 and 5 and 77 on dialysis. RESULTS: Significant bone pain that hindered activities of daily living was present in 58%, and 10% had at least one low-trauma fracture. CortBMD and cortical mineral content Z-scores were lower in dialysis compared with CKD patients (P = 0.004 and P = 0.02). DXA BMD hip and lumbar spine Z-scores did not correlate with CortBMD or biomarkers. CortBMD was negatively associated with parathyroid hormone (PTH; r = -0.44, P < 0.0001) and alkaline phosphatase (ALP; r = -0.22, P = 0.03) and positively with calcium (Ca; r = 0.33, P = 0.001). At PTH <3 times upper limit of normal, none of the patients had a CortBMD below -2 SD (odds ratio 95% confidence interval 7.331 to infinity). On multivariable linear regression PTH (ß = -0.43 , P < 0.0001), ALP (ß = -0.36, P < 0.0001) and Ca (ß = 0.21, P = 0.005) together predicted 57% of variability in CortBMD. DXA measures did not improve this model. CONCLUSIONS: Taken together, routinely used biomarkers, PTH, ALP and Ca, but not DXA, are moderate predictors of cortical BMD. DXA is not clinically useful and should not be routinely performed in children and young adults with CKD 4-5D.

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

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 (ß = +0.83 [95%CI +0.51 - +1.15] HD vs. HDF, p < 0.0001) and higher inter-dialytic-weight-gain (IDWG)% (ß = 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.

Influenza and pneumococcus vaccination rates in pediatric dialysis patients in Europe: recommendations vs reality A European Pediatric Dialysis Working Group and European Society for Pediatric Nephrology Dialysis Working Group study

Background/aim: Children on dialysis are under increased risk of influenza and invasive pneumococcal disease. Although vaccination against these microorganisms are recommended in dialysis patients and despite the fact that these vaccines can reduce disease burden and rates of hospitalization due to infection, vaccination rates are below expected and desired. We aimed to evaluate influenza and pneumococcal vaccination and infection rates in European pediatric dialysis centers. Materials and methods: In 16 centers from 11 countries, 357 pediatric dialysis patients were evaluated retrospectively during 1 year of observation period between 01.01.2014 and 01.01.2015. Results: In all centers, vaccination policy included immunization of dialysis patients with inactive influenza vaccine and pneumococcal conjugate vaccine (PCV). Fifty percent of the centers recommended pneumococcal polysaccharide vaccine following routine PCV series. A significantly higher pneumococcal vaccination rate (43.9%) was seen in peritoneal dialysis (PD) patients compared to those on hemodialysis (HD) (32.9%) (p = 0.035), while the rates for influenza were similar (42.4% and 46.1% respectively, p = 0.496). Among all dialysis patients, 2.2% (n = 8) developed pneumonia and 6.4% (n = 23) was infected by Influenza. Pneumococcic pneumonia rate was 5% for 140 patients who received antipneumococcal vaccine, while only one pneumonia episode was recorded out of 217 unvaccinated patients (p = 0.007). The influenza virus infection rates were similar for patients vaccinated and nonvaccinated (7 % and 6 %, respectively). Conclusions: Although influenza and pneumococcal vaccines are highly recommended in pediatric dialysis patients, vaccination rates were lower than expected. Pneumococcal vaccination rates were higher in PD compared to the patients on HD. The rate of children with influenza infection was higher than pneumonia. The efficacy of influenza and pneumococcal vaccines was highlighted by the low infection rates. Higher pneumonia rates in patients vaccinated against pneumococcus compared to unvaccinated ones might be due to coexisting risk factors.

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

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 ß2-microglobulin (ß2M) 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 ß2M 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 ß2M 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 ß2M levels remained steady in the hf-HD and lf-HD group, a decrease in ß2M was demonstrated for children on post-HDF (P<0.01). CONCLUSIONS: While post-HDF successfully decreased ß2M, 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.

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

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 ß2-microglobulin. The HDF cohort had lower ß2-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.

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

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/m2; 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.

Plasma Urotensin II levels in children and adolescents with chronic kidney disease: a single-centre study.

BACKGROUND: Increased plasma Urotensin II (UII) levels have been found in adults with renal diseases. Studies in children are scarce. The objective of the study is to estimate plasma UII levels in subjects with chronic kidney disease (CKD) stages 3 to 5 and renal transplant recipients (RTR). In addition, the correlation of UII with anthropometric features and biochemical parameters was assessed. METHODS: Fifty-four subjects, aged 3 to 20 years old, 23 with CKD, 13 with end-stage kidney disease (ESKD) undergoing hemodialysis (HD) and 18 RTR were enrolled. A detailed clinical evaluation was performed. Biochemical parameters of renal and liver function were measured. Plasma UII levels were measured in all patients and in 117 healthy controls, using a high sensitive enzyme immunoassay (EIA) kit. All data were analyzed using STATA™ (Version 10.1). RESULTS: Median UII and mean log-transformed UII levels were significantly higher in CKD and RTR patients compared to healthy subjects (p < 0.001). HD patients had higher but not statistically significant UII and log-UII levels than controls. UII levels increased significantly at the end of the HD session and were higher than controls and in line to those of other patients. The geometric scores of UII in HD (before dialysis), CKD and RTR patients increased respectively by 42, 136 and 164% in comparison with controls. Metabolic acidosis was associated with statistical significant change in log-UII levels (p = 0.001). Patients with metabolic acidosis had an increase in UII concentration by 76% compared to those without acidosis. CONCLUSIONS: Children and adolescents with CKD, particularly those who are not on HD and RTR, have significantly higher levels of UII than healthy subjects. UII levels increase significantly at the end of the HD session. The presence of metabolic acidosis affects significantly plasma UII levels.

Immunogenicity, Immunological Memory and Monitoring of Disease Activity Following an Anamnestic Immunization With the 13-Valent Pneumococcal Conjugate Vaccine in Children With Idiopathic Nephrotic Syndrome.

Anamnestic 13-valent pneumococcal conjugate vaccine immunization did not affect the relapse risk in pediatric idiopathic nephrotic syndrome. Pneumococcal serotype (PS)-specific antibody titers increased significantly in all groups. Children receiving immunomodulatory treatments (IMTs) displayed significantly lower levels of PS-specific antibodies for 3/8 serotypes tested. PS-specific B-cell counts significantly increased only in healthy controls and patients receiving corticosteroids.

Encapsulating peritoneal sclerosis in children on chronic PD: a survey from the European Paediatric Dialysis Working Group.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis (PD) that is associated with significant morbidity and mortality in adults. There are scarce data for children. We performed a 10-year survey to determine the prevalence, risk factors and outcome for EPS in children. METHODS: Chronic PD patients in 14 dialysis units participating in the European Paediatric Dialysis Working Group between January 2001 and December 2010 were included in this study. RESULTS: Twenty-two cases of EPS were reported (prevalence 1.5%; 8.7 per 1000 patient-years on PD). Median PD vintage was 5.9 (1.6-10.2) in EPS and 1.7 (0.7-7.7) years in the remainder of the PD population (P<0.0001). EPS patients had a significantly higher peritonitis rate than non-EPS patients (P=0.2). EPS was diagnosed while the child was on PD in 17 (77%), after conversion to haemodialysis (HD) in 3 and after transplantation in 2. Fifteen of 17 (88%) developed ultrafiltration (UF) failure. The median interval between UF failure and presentation with bowel obstruction was 2.8 (0.02-5.8) months. Twenty (91%) had clinical and radiological signs of bowel obstruction. Enterolysis was performed in 14 and 19 received immunosuppression or tamoxifen. Nine required parenteral nutrition. At final follow-up 4.8 (1.3-8.7) years after EPS diagnosis, 3 patients died, 11 had a functioning transplant and 8 were on HD. CONCLUSIONS: The prevalence of EPS in European children on PD is comparable with that of adult PD patients, but mortality from paediatric EPS is significantly lower. A high index of suspicion is required for the diagnosis of EPS in children with longer dialysis duration, a high peritonitis rate and UF failure.

Effect of Leflunomide on Treatment of Pediatric Renal Transplant Recipients With BK Virus Infection.

OBJECTIVES: Infection with the BK virus is a significant complication after renal transplant and can progress to BK virus nephropathy and graft dysfunction. There is no consensus on the management of BK virus infection in pediatric renal transplant recipients. The most common therapeutic option is immunosuppression reduction, which can increase rejection risk. We aimed to examine the effect of leflunomide, an agent with antiviral and immunosuppressive actions, in a case series of pediatric renal transplant recipients with BK virus infection. MATERIALS AND METHODS: Routine screening with blood BK virus DNA polymerase chain reaction was performed regularly in all of our renal transplant patients. When BK virus was detected, we reduced tacrolimus levels, discontinued mycophenolate mofetil, and started active treatment with leflunomide. Treatment with leflunomide was continued until BK virus was undetectable by polymerase chain reaction in at least 2 blood samples 2 weeks apart. RESULTS: All pediatric patients developed BK virus infection in a mean period of 3.9 months after transplant. Graft dysfunction was evident in all patients with 20% to 100% elevation of creatinine from baseline. Afterleflunomide initiation, all patients had undetectable levels of BK virus by plasma polymerase chain reaction in at least 2 different samples within a mean period of 3.4 months, and renal function had normalized back to the baseline. None of our patients had evidence of hepatotoxicity or anemia on regular monitoring, with no other adverse events. Renal function remained stable in the follow-up period with no reoccurrence of BK viremia up to the date of this writing. CONCLUSIONS: Treatment with leflunomide resulted in rapid BK virus clearance and preservation of renal function with no adverse effects.

Plasma Brain Natriuretic Peptide Levels in Children with Chronic Kidney Disease and Renal Transplant Recipients: A Single Center Study.

Pediatric chronic kidney disease (CKD) patients, as well as kidney transplant patients, are at an increased risk of developing cardiovascular disease. BNP measurement, as a biomarker of cardiovascular risk, has been recommended to this high-risk population. Plasma BNP levels were measured in 56 CKD children in either pre-dialysis stage, hemodialysis (HD) or renal transplant recipients (RTRs) and in 76 sex- and age-matched healthy controls. BNP levels were investigated in HD children, before and after the completion of their HD session. BNP levels in total CKD population, in pre-dialysis stage patients and on HD were significantly higher, compared to the respective controls. HD children had higher BNP levels compared to CKD patients in the pre-dialysis stage. Moreover, post-HD BNP concentration was slightly higher than pre-HD, with the difference being marginally statistically significant. BNP was positively correlated with eGFR, creatinine, cystatin-C and parathormone and negatively with albumin and 25-hydroxyvitamin D. A positive correlation between BNP concentration and the ratio of E/A in pulse-wave Doppler echocardiography was also observed. In conclusion, CKD pediatric patients, mainly those undergoing HD, have high plasma BNP levels which do not decrease after the HD session. This is indicative of a greater risk for future cardiovascular disease.

The burden of subclinical cardiovascular disease in children and young adults with chronic kidney disease and on dialysis.

BACKGROUND: Cardiovascular disease (CVD) is a common cause of morbidity and mortality even in young people with chronic kidney disease (CKD). We examined structural and functional CV changes in patients ˂30 years of age with CKD Stages 4 and 5 and on dialysis. METHODS: A total of 79 children and 21 young adults underwent cardiac computed tomography for coronary artery calcification (CAC), ultrasound for carotid intima-media thickness (cIMT), carotid-femoral pulse wave velocity (cfPWV) and echocardiography. Differences in structural (CAC, cIMT z-score, left ventricular mass index) and functional (carotid distensibility z-score and cfPWV z-score) measures were examined between CKD Stages 4 and 5 and dialysis patients. RESULTS: Overall, the cIMT z-score was elevated [median 2.17 (interquartile range 1.14-2.86)] and 10 (10%) had CAC. A total of 16/23 (69.5%) patients with CKD Stages 4 and 5 and 68/77 (88.3%) on dialysis had at least one structural or functional CV abnormality. There was no difference in the prevalence of structural abnormalities in CKD or dialysis cohorts, but functional abnormalities were more prevalent in patients on dialysis (P < 0.05). The presence of more than one structural abnormality was associated with a 4.5-fold increased odds of more than one functional abnormality (95% confidence interval 1.3-16.6; P < 0.05). Patients with structural and functional abnormalities [cIMT z-score >2 standard deviation (SD) or distensibility <-2 SD) had less carotid dilatation (lumen:wall cross-sectional area ratio) compared with those with normal cIMT and distensibility. CONCLUSIONS: There is a high burden of subclinical CVD in young CKD patients, with a greater prevalence of functional abnormalities in dialysis compared with CKD patients. Longitudinal studies are required to test these hypothesis-generating data and define the trajectory of CV changes in CKD.

Hemodiafiltration Is Associated With Reduced Inflammation and Increased Bone Formation Compared With Conventional Hemodialysis in Children: The HDF, Hearts and Heights (3H) Study.

BACKGROUND: Patients on dialysis have a high burden of bone-related comorbidities, including fractures. We report a post hoc analysis of the prospective cohort study HDF, Hearts and Heights (3H) to determine the prevalence and risk factors for chronic kidney disease-related bone disease in children on hemodiafiltration (HDF) and conventional hemodialysis (HD). METHODS: The baseline cross-sectional analysis included 144 children, of which 103 (61 HD, 42 HDF) completed 12-month follow-up. Circulating biomarkers of bone formation and resorption, inflammatory markers, fibroblast growth factor-23, and klotho were measured. RESULTS: Inflammatory markers interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein were lower in HDF than in HD cohorts at baseline and at 12 months (P < .001). Concentrations of bone formation (bone-specific alkaline phosphatase) and resorption (tartrate-resistant acid phosphatase 5b) markers were comparable between cohorts at baseline, but after 12-months the bone-specific alkaline phosphatase/tartrate-resistant acid phosphatase 5b ratio increased in HDF (P = .004) and was unchanged in HD (P = .44). On adjusted analysis, the bone-specific alkaline phosphatase/tartrate-resistant acid phosphatase 5b ratio was 2.66-fold lower (95% confidence interval, -3.91 to -1.41; P < .0001) in HD compared with HDF. Fibroblast growth factor-23 was comparable between groups at baseline (P = .52) but increased in HD (P < .0001) and remained unchanged in HDF (P = .34) at 12 months. Klotho levels were similar between groups and unchanged during follow-up. The fibroblast growth factor-23/klotho ratio was 3.86-fold higher (95% confidence interval, 2.15-6.93; P < .0001) after 12 months of HD compared with HDF. CONCLUSION: Children on HDF have an attenuated inflammatory profile, increased bone formation, and lower fibroblast growth factor-23/klotho ratios compared with those on HD. Long-term studies are required to determine the effects of an improved bone biomarker profile on fracture risk and cardiovascular health.

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

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 ß2-microglobulin (ß2M) 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 (rs). We found higher levels of ß2M, 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 ß2M, pCG, HA, IAA, IxS, and CMPF (rs -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.

Vaccination Practices in Pediatric Dialysis Patients Across Europe. A European Pediatric Dialysis Working Group and European Society for Pediatric Nephrology Dialysis Working Group Study.

BACKGROUND: Data on the immunization practices in pediatric chronic kidney disease (CKD) patients are scarce. The purpose of this study was to evaluate current vaccination practices for children on dialysis across European pediatric nephrology centers. METHODS: A total of 18 tertiary pediatric nephrology centers from 12 European countries were included in the study. The data on universal national immunization programs and immunization practices for children with chronic disease or risk were recorded from European Center for Disease Prevention and Control and the World Health Organization. The immunization practices and center protocols for monitoring antibody titers after vaccination in dialysis patients were obtained through a questionnaire. RESULTS: All centers included in the study recommended immunization against hepatitis B virus (HBV), diphtheria, tetanus, pertussis, Hemophilus influenzae type b (Hib), poliomyelitis, measles, mumps, rubella (MMR), and streptococcus pneumonia in dialysis patients. In 16 centers, dialysis patients were vaccinated against influenza virus annually. HBV protective antibody titers were measured in 17 centers (during dialysis period in 14 centers, during pre-renal transplantation preparations in 14 centers or in both times in 11 centers). Hepatitis A virus (HAV) was reported to be followed in 13 centers, in 8 centers during dialysis period, and in 11 centers during pre-RTx preparations. MMR and varicella-zoster virus (VZV) protective antibody titers were measured during the dialysis period or before renal transplantation (RTx) in 12 and 15 centers, respectively, and in 6 centers both titers were checked both times. CONCLUSION: There are variations in vaccination practice across Europe. Children with CKD, those undergoing dialysis, and transplant candidates should receive age-appropriate vaccinations before RTx as well as before the transition to adult nephrology clinics and antibody levels should be monitored to evaluate the immunization status before and after RTx.

Safety and immunogenicity of booster immunization with 7-valent pneumococcal conjugate vaccine in children with idiopathic nephrotic syndrome.

Safety and immunogenicity of a booster dose of 7-valent pneumococcal conjugate vaccine (PCV7) were evaluated in 29 patients with idiopathic nephrotic syndrome (INS), who had been primed 12 months earlier with one dose of PCV7. PCV7 was not associated with increased risk of INS relapse (RR=0.77, p=0.8) and serotype-specific antibodies increased in all subjects at 1 month (p<0.01). The quantitative characteristics of immune response and the effect of treatment with mycophenolate mofetil and/or cyclosporine A following booster PCV7 were similar with primary response. Additional PCV7 doses could be safely given in children with INS to increase circulating antibodies above the protective threshold.

Safety, immunogenicity and kinetics of immune response to 7-valent pneumococcal conjugate vaccine in children with idiopathic nephrotic syndrome.

Safety, immunogenicity and kinetics of 7-valent pneumococcal-conjugate vaccine (PCV7) immune response were evaluated in 33 children with idiopathic nephrotic syndrome (INS) and 16 controls. PCV7 was not associated with increased risk of relapse (RR=0.80, p=0.61). Serotype (PS)-specific antibodies increased in all subjects at 1 month (p<0.01) with inferior immunogenicity for 3/7 PS in patients on immunomodulators (p<0.02). Most patients retained protective antibodies at 12-14 months although at lower levels for 4/7 PS (p<0.08). Different PS kinetics in INS suggests antibody monitoring and revaccination when necessary for protection from pneumococcal infections.