Multicenter Long-Term Real World Data on Treatment With Lumasiran in Patients With Primary Hyperoxaluria Type 1.

Introduction: The RNA interference (RNAi) medication lumasiran reduces hepatic oxalate production in primary hyperoxaluria type 1 (PH1). Data outside clinical trials are scarce. Methods: We report on retrospectively and observationally obtained data in 33 patients with PH1 (20 with preserved kidney function, 13 on dialysis) treated with lumasiran for a median of 18 months. Results: Among those with preserved kidney function, mean urine oxalate (Uox) decreased from 1.88 (baseline) to 0.73 mmol/1.73 m2 per 24h after 3 months, to 0.72 at 12 months, and to 0.65 at 18 months, but differed according to vitamin B6 (VB6) medication. The highest response was at month 4 (0.55, -70.8%). Plasma oxalate (Pox) remained stable over time. Glomerular filtration rate increased significantly by 10.5% at month 18. Nephrolithiasis continued active in 6 patients, nephrocalcinosis ameliorated or progressed in 1 patient each. At last follow-up, Uox remained above 1.5 upper limit of normal (>0.75 mmol/1.73 m2 per 24h) in 6 patients. Urinary glycolate (Uglyc) and plasma glycolate (Pglyc) significantly increased in all, urine citrate decreased, and alkali medication needed adaptation. Among those on dialysis, mean Pox and Pglyc significantly decreased and increased, respectively after monthly dosing (Pox: 78-37.2, Pglyc: 216.4-337.4 µmol/l). At quarterly dosing, neither Pox nor Pglyc were significantly different from baseline levels. An acid state was buffered by an increased dialysis regimen. Systemic oxalosis remained unchanged. Conclusion: Lumasiran treatment is safe and efficient. Dosage (interval) adjustment necessities need clarification. In dialysis, lack of Pox reduction may relate to dissolving systemic oxalate deposits. Pglyc increment may be a considerable acid load requiring careful consideration, which definitively needs further investigation.

Diversity of kidney care referral pathways in national child health systems of 48 European countries.

Background: Primary, secondary and tertiary healthcare services in Europe create complex networks covering pediatric subspecialties, sociology, economics and politics. Two surveys of the European Society for Paediatric Nephrology (ESPN) in 1998 and 2017 revealed substantial disparities of kidney care among European countries. The purpose of the third ESPN survey is to further identify national differences in the conceptualization and organization of European pediatric kidney health care pathways during and outside normal working hours. Methods: In 2020, a questionnaire was sent to one leading pediatric nephrologist from 48 of 53 European countries as defined by the World Health Organization. In order to exemplify care pathways in pediatric primary care nephrology, urinary tract infection (UTI) was chosen. Steroid sensitive nephrotic syndrome (SSNS) was chosen for pediatric rare disease nephrology and acute kidney injury (AKI) was analyzed for pediatric emergency nephrology. Results: The care pathways for European children and young people with urinary tract infections were variable and differed during standard working hours and also during night-time and weekends. During daytime, UTI care pathways included six different types of care givers. There was a shift from primary care services outside standard working hours to general outpatient polyclinic and hospital services. Children with SNSS were followed up by pediatric nephrologists in hospitals in 69% of countries. Patients presenting with community acquired AKI were admitted during regular working hours to secondary or tertiary care hospitals. During nights and weekends, an immediate shift to University Children's Hospitals was observed where treatment was started by intensive care pediatricians and pediatric nephrologists. Conclusion: Gaps and fragmentation of pediatric health services may lead to the risk of delayed or inadequate referral of European children with kidney disease to pediatric nephrologists. The diversity of patient pathways outside of normal working hours was identified as one of the major weaknesses in the service chain.

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.

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.

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.

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.

Countermeasures against COVID-19: how to navigate medical practice through a nascent, evolving evidence base - a European multicentre mixed methods study.

OBJECTIVES: In a previously published Delphi exercise the European Pediatric Dialysis Working Group (EPDWG) reported widely variable counteractive responses to COVID-19 during the first week of statutory public curfews in 12 European countries with case loads of 4-680 infected patients per million. To better understand these wide variations, we assessed different factors affecting countermeasure implementation rates and applied the capability, opportunity, motivation model of behaviour to describe their determinants. DESIGN: We undertook this international mixed methods study of increased depth and breadth to obtain more complete data and to better understand the resulting complex evidence. SETTING: This study was conducted in 14 paediatric nephrology centres across 12 European countries during the COVID-19 pandemic. PARTICIPANTS: The 14 participants were paediatric nephrologists and EPDWG members from 12 European centres. MAIN OUTCOME MEASURES: 52 countermeasures clustered into eight response domains (access control, patient testing, personnel testing, personal protective equipment policy, patient cohorting, personnel cohorting, suspension of routine care, remote work) were categorised by implementation status, drivers (expert opinion, hospital regulations) and resource dependency. Governmental strictness and media attitude were independently assessed for each country and correlated with relevant countermeasure implementation factors. RESULTS: Implementation rates varied widely among response domains (median 49.5%, range 20%-71%) and centres (median 46%, range 31%-62%). Case loads were insufficient to explain response rate variability. Increasing case loads resulted in shifts from expert opinion-based to hospital regulation-based decisions to implement additional countermeasures despite increased resource dependency. Higher governmental strictness and positive media attitude towards countermeasure implementation were associated with higher implementation rates. CONCLUSIONS: COVID-19 countermeasure implementation by paediatric tertiary care centres did not reflect case loads but rather reflected heterogeneity of local rules and of perceived resources. These data highlight the need of ongoing reassessment of current practices, facilitating rapid change in 'institutional behavior' in response to emerging evidence of countermeasure efficacy.

Update on the creation and maintenance of arteriovenous fistulas for haemodialysis in children.

Arteriovenous fistulas (AVFs) are widely used for haemodialysis (HD) in adults with stage 5 chronic kidney disease (CKD 5) and are generally considered the best form of vascular access (VA). The 'Fistula First' initiative in 2003 helped to change the culture of VA in adults. However, this cultural change has not yet been adopted in children despite the fact that a functioning AVF is associated with lower complication rates and longer access survival than a central venous line (CVL). For children with CKD 5, especially when kidney failure starts early in life, there is a risk that all VA options will be exhausted. Therefore, it is essential to develop long-term strategies for optimal VA creation and maintenance. Whilst AVFs are the preferred VA in the paediatric population on chronic HD, they may not be suitable for every child. Recent guidelines and observational data in the paediatric CKD 5 population recommend switching from a 'Catheter First' to 'Catheter Last' approach. In this review, recent evidence is summarized in order to promote change in current practices.

Antibody-mediated rejection with the presence of glomerular crescents in a pediatric kidney transplant recipient: A case report.

Glomerular crescents in kidney transplantation are indicative of severe glomerular injury and constitute a hallmark of RPGN. Their concurrence with ABMR has been rarely described only in adult patients. We report a case of 10-year-old boy with compound heterozygous Fin-major Finnish-type congenital nephrotic syndrome, who had received a deceased-donor kidney transplant 5 years before onset of acute kidney injury and nephrotic range proteinuria without hematuria. Kidney allograft biopsy illustrated 6 glomeruli with global sclerosis and 6 with remarkable circumferential or segmental cellular crescents. Negative glomerular immunofluorescence for immune-complex deposits and the absence of serum ANCA eliminated the presence of immune-mediated and ANCA-positive pauci-immune crescentic glomerulonephritis. Diagnosis of ABMR was based on the high levels of HLA class II DSA and the histological evidence of glomerulitis, peritubular capillaritis, and acute tubular injury with positive linear peritubular capillary C4d staining. The patient despite plasmapheresis and enhanced immunosuppressive treatment progressed to end-stage renal disease. We conclude that glomerular crescents may represent a finding of AMBR and possibly a marker of poor allograft prognosis in pediatric patients.

Rapid response in the COVID-19 pandemic: a Delphi study from the European Pediatric Dialysis Working Group.

BACKGROUND: COVID-19 was declared a global health emergency. Since children are less than 1% of reported cases, there is limited information to develop evidence-based practice recommendations. The objective of this study was to rapidly gather expert knowledge and experience to guide the care of children with chronic kidney disease during the COVID-19 pandemic. METHODS: A four-round multi-center Delphi exercise was conducted among 13 centers in 11 European countries of the European Pediatric Dialysis Working Group (EPDWG) between March, 16th and 20th 2020. Results were analyzed using a mixed methods qualitative approach and descriptive statistics. RESULTS: Thirteen COVID-19 specific topics of particular need for guidance were identified. Main themes encompassed testing strategies and results (n = 4), changes in use of current therapeutics (n = 3), preventive measurements of transmission and management of COVID-19 (n = 3), and changes in standard clinical care (n = 3). Patterns of center-specific responses varied according to regulations and to availability of guidelines. CONCLUSIONS: As limited quantitative evidence is available in real time during the rapid spread of the COVID-19 pandemic, qualitative expert knowledge and experience represent the best evidence available. This Delphi exercise demonstrates that use of mixed methodologies embedded in an established network of experts allowed prompt analysis of pediatric nephrologists' response to COVID-19 during this fast-emerging public health crisis. Such rapid sharing of knowledge and local practices is essential to timely and optimal guidance for medical management of specific patient groups in multi-country health care systems such as those of Europe and the US.

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.

Vascular access in children requiring maintenance haemodialysis: a consensus document by the European Society for Paediatric Nephrology Dialysis Working Group

There are three principle forms of vascular access available for the treatment of children with end stage kidney disease (ESKD) by haemodialysis: tunnelled catheters placed in a central vein (central venous lines, CVLs), arteriovenous fistulas (AVF), and arteriovenous grafts (AVG) using prosthetic orbiological material. Compared with the adult literature, there are few studies in children to provide evidence based guidelines for optimal vascular access type or its management and outcomes in children with ESKD.

Association between timing of dialysis initiation and clinical outcomes in the paediatric population: an ESPN/ERA-EDTA registry study.

BACKGROUND: There is no consensus regarding the timing of dialysis therapy initiation for end-stage kidney disease (ESKD) in children. As studies investigating the association between timing of dialysis initiation and clinical outcomes are lacking, we aimed to study this relationship in a cohort of European children who started maintenance dialysis treatment. METHODS: We used data on 2963 children from 21 different countries included in the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry who started renal replacement therapy before 18 years of age between 2000 and 2014. We compared two groups according to the estimated glomerular filtration rate (eGFR) at start: eGFR ≥8 mL/min/1.73 m2 (early starters) and eGFR <8 mL/min/1.73 m2 (late starters). The primary outcomes were patient survival and access to transplantation. Secondary outcomes were growth and cardiovascular risk factors. Sensitivity analyses were performed to account for selection- and lead time-bias. RESULTS: The median eGFR at the start of dialysis was 6.1 for late versus 10.5 mL/min/1.73 m2 for early starters. Early starters were older [median: 11.0, interquartile range (IQR): 5.7-14.5 versus 9.4, IQR: 2.6-14.1 years]. There were no differences observed between the two groups in mortality and access to transplantation at 1, 2 and 5 years of follow-up. One-year evolution of height standard deviation scores was similar among the groups, whereas hypertension was more prevalent among late initiators. Sensitivity analyses resulted in similar findings. CONCLUSIONS: We found no evidence for a clinically relevant benefit of early start of dialysis in children with ESKD. Presence of cardiovascular risk factors, such as high blood pressure, should be taken into account when deciding to initiate or postpone dialysis in children with ESKD, as this affects the survival.

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.

Vascular Access Choice, Complications, and Outcomes in Children on Maintenance Hemodialysis: Findings From the International Pediatric Hemodialysis Network (IPHN) Registry.

RATIONALE & OBJECTIVE: Arteriovenous fistulas (AVFs) have been recommended as the preferred vascular access for pediatric patients on maintenance hemodialysis (HD), but data comparing AVFs with other access types are scant. We studied vascular access choice, placement, complications, and outcomes in children. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 552 children and adolescents from 27 countries on maintenance HD followed up prospectively by the International Pediatric HD Network (IPHN) Registry between 2012 and 2017. PREDICTOR: Type of vascular access: AVF, central venous catheter (CVC), or arteriovenous graft. OUTCOME: Infectious and noninfectious vascular access complication rates, dialysis performance, biochemical and hematologic parameters, and clinical outcomes. ANALYTICAL APPROACH: Univariate and multivariable linear mixed models, generalized linear mixed models, and proportional hazards models; cumulative incidence functions. RESULTS: During 314 cumulative patient-years, 628 CVCs, 225 AVFs, and 17 arteriovenous grafts were placed. One-third of the children with an AVF required a temporary CVC until fistula maturation. Vascular access choice was associated with age and expectations for early transplantation. There was a 3-fold higher living related transplantation rate and lower median time to transplantation of 14 (IQR, 6-23) versus 20 (IQR, 14-36) months with CVCs compared with AVFs. Higher blood flow rates and Kt/Vurea were achieved with AVFs than with CVCs. Infectious complications were reported only with CVCs (1.3/1,000 catheter-days) and required vascular access replacement in 47%. CVC dysfunction rates were 2.5/1,000 catheter-days compared to 1.2/1,000 fistula-days. CVCs required 82% more revisions and almost 3-fold more vascular access replacements to a different site than AVFs (P<0.001). LIMITATIONS: Clinical rather than population-based data. CONCLUSIONS: CVCs are the predominant vascular access choice in children receiving HD within the IPHN. Age-related anatomical limitations and expected early living related transplantation were associated with CVC use. CVCs were associated with poorer dialysis efficacy, higher complication rates, and more frequent need for vascular access replacement. Such findings call for a re-evaluation of pediatric CVC use and practices.

Vascular access in children requiring maintenance haemodialysis: a consensus document by the European Society for Paediatric Nephrology Dialysis Working Group.

BACKGROUND: There are three principle forms of vascular access available for the treatment of children with end stage kidney disease (ESKD) by haemodialysis: tunnelled catheters placed in a central vein (central venous lines, CVLs), arteriovenous fistulas (AVF), and arteriovenous grafts (AVG) using prosthetic or biological material. Compared with the adult literature, there are few studies in children to provide evidence based guidelines for optimal vascular access type or its management and outcomes in children with ESKD. METHODS: The European Society for Paediatric Nephrology Dialysis Working Group (ESPN Dialysis WG) have developed recommendations for the choice of access type, pre-operative evaluation, monitoring, and prevention and management of complications of different access types in children with ESKD. RESULTS: For adults with ESKD on haemodialysis, the principle of "Fistula First" has been key to changing the attitude to vascular access for haemodialysis. However, data from multiple observational studies and the International Paediatric Haemodialysis Network registry suggest that CVLs are associated with a significantly higher rate of infections and access dysfunction, and need for access replacement. Despite this, AVFs are used in only ∼25% of children on haemodialysis. It is important to provide the right access for the right patient at the right time in their life-course of renal replacement therapy, with an emphasis on venous preservation at all times. While AVFs may not be suitable in the very young or those with an anticipated short dialysis course before transplantation, many paediatric studies have shown that AVFs are superior to CVLs. CONCLUSIONS: Here we present clinical practice recommendations for AVFs and CVLs in children with ESKD. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system has been used to develop and GRADE the recommendations. In the absence of high quality evidence, the opinion of experts from the ESPN Dialysis WG is provided, but is clearly GRADE-ed as such and must be carefully considered by the treating physician, and adapted to local expertise and individual patient needs as appropriate.

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.

Management of children with congenital nephrotic syndrome: challenging treatment paradigms.

BACKGROUND: Management of children with congenital nephrotic syndrome (CNS) is challenging. Bilateral nephrectomies followed by dialysis and transplantation are practiced in most centres, but conservative treatment may also be effective. METHODS: We conducted a 6-year review across members of the European Society for Paediatric Nephrology Dialysis Working Group to compare management strategies and their outcomes in children with CNS. RESULTS: Eighty children (50% male) across 17 tertiary nephrology units in Europe were included (mutations in NPHS1, n = 55; NPHS2, n = 1; WT1, n = 9; others, n = 15). Excluding patients with mutations in WT1, antiproteinuric treatment was given in 42 (59%) with an increase in S-albumin in 70% by median 6 (interquartile range: 3-8) g/L (P < 0.001). Following unilateral nephrectomy, S-albumin increased by 4 (1-8) g/L (P = 0.03) with a reduction in albumin infusion dose by 5 (2-9) g/kg/week (P = 0.02). Median age at bilateral nephrectomies (n = 29) was 9 (7-16) months. Outcomes were compared between two groups of NPHS1 patients: those who underwent bilateral nephrectomies (n = 25) versus those on conservative management (n = 17). The number of septic or thrombotic episodes and growth were comparable between the groups. The response to antiproteinuric treatment, as well as renal and patient survival, was independent of NPHS1 mutation type. At final follow-up (median age 34 months) 20 (80%) children in the nephrectomy group were transplanted and 1 died. In the conservative group, 9 (53%) remained without dialysis, 4 (24%; P < 0.001) were transplanted and 2 died. CONCLUSION: An individualized, stepwise approach with prolonged conservative management may be a reasonable alternative to early bilateral nephrectomies and dialysis in children with CNS and NPHS1 mutations. Further prospective studies are needed to define indications for unilateral nephrectomy.

Fever duration during treated urinary tract infections and development of permanent renal lesions.

OBJECTIVE: To assess the effect of the duration of fever after the initiation of treatment (FAT) of febrile urinary tract infections (UTI) on the development of permanent renal lesions based on dimercaptosuccinic acid (DMSA) scintigraphy findings. To evaluate the FAT contribution to permanent renal lesion formation in relation to fever before treatment initiation (FBT), the presence of vesicourinary reflux (VUR), age and severity of infection. METHODS: The inpatient records of 148 children (median age: 2.4 months (11 days to 24 months)) with a first episode of UTI during a 3-year period were analysed. DMSA findings, and clinical and laboratory parameters were evaluated. RESULTS: Among the study population, 34/148 (22.97%) children had permanent renal lesions on the DMSA scan 6 months after a single episode of UTI. Twenty-three children (15.5%) had mild, 10 (6.7%) had moderate and 1 (0.6%) child had severe lesions on the DMSA. FAT prolongation >/48 hours was associated with older age (p=0.01) and increased absolute neutrophil count (p=0.042). The likelihood of lesions was significantly increased when FAT was ≥48 hours (R2=0.043, p=0.021). On multiple regression analysis, with the addition of FBT>/72 hours (0.022), the presence of VUR (p<0.001), C-reactive protein (p=0.027) and age (p=0.031), the effect of FAT on lesion development disappeared (p=0.15). CONCLUSIONS: Prolongation of FAT≥48 hours of febrile UTI in children <2 years significantly contributes to the development of permanent renal lesions. However, delay in treatment initiation >/72 hours, the presence of VUR, older age and infection severity seem to be more significant predictors of the development of renal lesions.

Factors affecting mortality in children requiring continuous renal replacement therapy in pediatric intensive care unit.

BACKGROUND: Acute kidney injury (AKI) occurs in up to 30% of pediatric intensive care unit (PICU) patients and is associated with a high mortality rate. OBJECTIVES: The objective of the study was to evaluate factors associated with the outcome and to identify the prognostic factors in children receiving continuous renal replacement therapy (CRRT). MATERIAL AND METHODS: This was a retrospective, single-center study, including 46 patients. RESULTS: Logistic regression analysis demonstrated significant effects on patient survival exerted by the percentage of fluid overload (FO%) (odds ratio (OR): 1.030; p = 0.044). In the group of patients with FO% < 25%, the mortality was 33.3%, and in the FO% ≥ 25% group, the mortality was 67.9% (p < 0.001). The probability of death without multi-organ failure (MOF) was 13%, while with MOF it was 74%. There was no difference in the duration of hospitalization between the CRRT patients (mean: 21.9 days) and the general population of children hospitalized in PICU in the same period (n = 3,255; mean: 25.4 days); however, a significant difference was noted in mortality between the 2 groups of patients (54% vs 6.5%; p < 0.001). CONCLUSIONS: The mortality of PICU CRRT patients is more than 8-fold higher than the mortality of the total PICU population. Coexisting MOF increases the mortality almost 6 times. The mortality of children with FO% ≥ 25% was more than 2-fold higher than the mortality of children with FO% < 25%.