Incidence and outcomes of kidney replacement therapy for end-stage kidney disease due to primary glomerular disease in Europe: findings from the ERA Registry.

BACKGROUND AND HYPOTHESIS: Primary glomerular disease (PGD) is a major cause of end-stage kidney disease (ESKD) leading to kidney replacement therapy (KRT). We aimed to describe incidence (trends) in individuals starting KRT for ESKD due to PGD and to examine their survival and causes of death. METHODS: We used data from the European Renal Association (ERA) Registry on 69 854 patients who started KRT for ESKD due to PGD between 2000 and 2019. ERA primary renal disease codes were used to define six PGD subgroups. We examined age and sex standardized incidence, trend of the incidence, and survival. RESULTS: The standardized incidence of KRT for ESKD due to PGD was 16.6 per million population (pmp), ranging from 8.6 pmp in Serbia to 20.0 pmp in France. IgA nephropathy (IgAN) and focal segmental glomerulosclerosis (FSGS) had the highest incidence of 4.6 pmp and 2.6 pmp, respectively. Histologically non-examined PGDs represented over 50% of cases in Serbia, Bosnia and Herzegovina, and Romania and were also common in Greece, Estonia, Belgium, and Sweden. The incidence declined from 18.6 pmp in 2000 to 14.5 pmp in 2013, after which it stabilized. All PGD subgroups had five-year survival probabilities above 50%, with crescentic glomerulonephritis having the highest risk of death (adjusted hazard ratio: 1.8 [95% confidence interval: 1.6-1.9]) compared with IgAN. Cardiovascular disease was the most common cause of death (33.9%). CONCLUSION: The incidence of KRT for ESKD due to PGD showed large differences between countries and was highest and increasing for IgAN and FSGS. Lack of kidney biopsy facilities in some countries may have affected accurate assignment of the cause of ESKD. The recognition of the incidence and outcomes of KRT among different PGD subgroups may contribute to a more individualized patient care approach.

Technical requirements and devices available for long-term hemodialysis in children-mind the gap!

Children requiring long-term kidney replacement therapy are a "rare disease" cohort. While the basic technical requirements for hemodialysis (HD) are similar in children and adults, key aspects of the child's cardiovascular anatomy and hemodynamic specifications must be considered. In this article, we describe the technical requirements for long-term HD therapy for children and the devices that are currently available around the world. We highlight the characteristics and major technical shortcomings of permanent central venous catheters, dialyzers, dialysis machines, and software available to clinicians who care for children. We show that currently available HD machines are not equipped with appropriately small circuits and sensitive control mechanisms to perform safe and effective HD in the youngest patients. Manufacturers limit their liability, and health regulatory agencies permit the use of devices, only in children according to the manufacturers' pre-specified weight limitations. Although registries show that 6-23% of children starting long-term HD weigh less than 15 kg, currently, there is only one long-term HD device that is cleared for use in children weighing 10 to 15 kg and none is available and labelled for use in children weighing less than 10 kg anywhere in the world. Thus, many children are being treated "off-label" and are subject to interventions delivered by medical devices that lack pediatric safety and efficacy data. Moreover, recent improvements in dialysis technology offered to adult patients are denied to most children. We, in turn, advocate for concerted action by pediatric nephrologists, industry, and health regulatory agencies to increase the development of dedicated HD machines and equipment for children.

Factors influencing circuit lifetime in paediatric continuous kidney replacement therapies - results from the EurAKId registry.

BACKGROUND: Continuous kidney replacement therapy (CKRT) has recently become the preferred kidney replacement modality for children with acute kidney injury (AKI). We hypothesise that CKRT technical parameters and treatment settings in addition to the clinical characteristics of patients may influence the circuit lifetime in children. METHODS: The study involved children included in the EurAKId registry (NCT02960867), who underwent CKRT treatment. We analysed patient characteristics and CKRT parameters. The primary end point was mean circuit lifetime (MCL). Secondary end points were number of elective circuit changes and occurrence of dialysis-related complications. RESULTS: The analysis was composed of 247 children who underwent 37,562 h of CKRT (median 78, IQR 37-165 h per patient). A total of 1357 circuits were utilised (3, IQR 2-6 per patient). MCL was longer in regional citrate anticoagulation (RCA), compared to heparin (HA) and no anticoagulation (NA) (42, IQR 32-58 h; 24, IQR 14-34 h; 18, IQR 12-24 h, respectively, p < 0.001). RCA was associated with longer MCL regardless of the patient's age or dialyser surface. In multivariate analysis, MCL correlated with dialyser surface area (beta = 0.14, p = 0.016), left internal jugular vein vascular access site (beta = -0.37, p = 0.027), and the use of HA (beta = -0.14, p = 0.038) or NA (beta = -0.37, p < 0.001) vs. RCA. RCA was associated with the highest ratio of elective circuit changes and the lowest incidence of complications. CONCLUSION: Anticoagulation modality, dialyser surface, and vascular access site influence MCL. RCA should be considered when choosing first-line anticoagulation for CKRT in children. Further efforts should focus on developing guidelines and clinical practice recommendations for paediatric CKRT.

Pediatric kidney transplantation: is it safe to perform during night-time or day-off?

PURPOSE: To investigate the impact of after-hours surgery on the outcomes of pediatric kidney transplantation (KT). METHODS: Medical records of pediatric KTs performed at a single institution between 2013 and 2021 were retrospectively reviewed. The population was split into three groups according to the incision time and calendar: ordinary day (8.00 AM - 6.30 PM), day-off, and night-time (6.30 PM - 8.00 AM). The following endpoints were compared: ischemia times, length of surgery, complications, delayed graft function (DGF), primary graft non-function (PGNF), and eGFR at three-month follow-up. RESULTS: Ninety-six non-living donor KTs were performed, median age 11 (IQR 4.3-14) years and median body weight 26 (IQR 13-50) kg. Forty-one (43%) were performed during night-time and 28 (29%) during day-off. Ischemia times were similar (p = 0.769, p = 0.536). Day-off KTs presented an extended length of surgery (p = 0.011). Thirty-two complications were reported in 31 KTs. No difference in the overall rate of complications, DGF, PNGF, and three-month eGFR was found (p = 0.669, p = 0.383, p = 0.949, p = 0.093). Post-operative bleedings were more common in days-off (p = 0.003). CONCLUSION: The number of pediatric KTs performed during after-hours was considerable. Even though similar outcomes were reported, more caution should be focused on the KTs performed in days-off to avoid severe complications.

Diagnosis and management of mineral and bone disorders in infants with CKD: clinical practice points from the ESPN CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce.

BACKGROUND: Infants with chronic kidney disease (CKD) form a vulnerable population who are highly prone to mineral and bone disorders (MBD) including biochemical abnormalities, growth retardation, bone deformities, and fractures. We present a position paper on the diagnosis and management of CKD-MBD in infants based on available evidence and the opinion of experts from the European Society for Paediatric Nephrology (ESPN) CKD-MBD and Dialysis working groups and the Pediatric Renal Nutrition Taskforce. METHODS: PICO (Patient, Intervention, Comparator, Outcomes) questions were generated, and relevant literature searches performed covering a population of infants below 2 years of age with CKD stages 2-5 or on dialysis. Clinical practice points (CPPs) were developed and leveled using the American Academy of Pediatrics grading matrix. A Delphi consensus approach was followed. RESULTS: We present 34 CPPs for diagnosis and management of CKD-MBD in infants, including dietary control of calcium and phosphate, and medications to prevent and treat CKD-MBD (native and active vitamin D, calcium supplementation, phosphate binders). CONCLUSION: As there are few high-quality studies in this field, the strength of most statements is weak to moderate, and may need to be adapted to individual patient needs by the treating physician. Research recommendations to study key outcome measures in this unique population are suggested. A higher resolution version of the Graphical abstract is available as Supplementary information.

Associations of longitudinal height and weight with clinical outcomes in pediatric kidney replacement therapy: results from the ESPN/ERA Registry.

BACKGROUND: Associations between anthropometric measures and patient outcomes in children are inconsistent and mainly based on data at kidney replacement therapy (KRT) initiation. We studied associations of height and body mass index (BMI) with access to kidney transplantation, graft failure, and death during childhood KRT. METHODS: We included patients < 20 years starting KRT in 33 European countries from 1995-2019 with height and weight data recorded to the ESPN/ERA Registry. We defined short stature as height standard deviation scores (SDS) < -1.88 and tall stature as height SDS > 1.88. Underweight, overweight and obesity were calculated using age and sex-specific BMI for height-age criteria. Associations with outcomes were assessed using multivariable Cox models with time-dependent covariates. RESULTS: We included 11,873 patients. Likelihood of transplantation was lower for short (aHR: 0.82, 95% CI: 0.78-0.86), tall (aHR: 0.65, 95% CI: 0.56-0.75), and underweight patients (aHR: 0.79, 95%CI: 0.71-0.87). Compared with normal height, patients with short and tall statures showed higher graft failure risk. All-cause mortality risk was higher in short (aHR: 2.30, 95% CI: 1.92-2.74), but not in tall stature. Underweight (aHR: 1.76, 95% CI: 1.38-2.23) and obese (aHR: 1.49, 95% CI: 1.11-1.99) patients showed higher all-cause mortality risk than normal weight subjects. CONCLUSIONS: Short and tall stature and being underweight were associated with a lower likelihood of receiving a kidney allograft. Mortality risk was higher among pediatric KRT patients with a short stature or those being underweight or obese. Our results highlight the need for careful nutritional management and multidisciplinary approach for these patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Sodium intake and urinary losses in children on dialysis: a European multicenter prospective study.

BACKGROUND: Sodium (Na) balance is unexplored in dialyzed children. We assessed a simplified sodium balance (sNaB) and its correlates in pediatric patients receiving maintenance dialysis. METHODS: Patients < 18 years old on hemodialysis (HD) or peritoneal dialysis (PD) in six European Pediatric Dialysis Working Group centers were recruited. sNaB was calculated from enteral Na, obtained by a 3-day diet diary, Na intake from medications, and 24-h urinary Na (uNa). Primary outcomes were systolic blood pressure and diastolic blood pressure standard deviation scores (SBP and DBP SDS), obtained by 24-h ambulatory blood pressure monitoring or office BP according to age, and interdialytic weight gain (IDWG). RESULTS: Forty-one patients (31 HD), with a median age of 13.3 (IQR 5.2) years, were enrolled. Twelve patients (29.3%) received Na-containing drugs, accounting for 0.6 (0.7) mEq/kg/day. Median total Na intake was 1.5 (1.1) mEq/kg/day, corresponding to 60.6% of the maximum recommended daily intake for healthy children. Median uNa and sNaB were 0.6 (1.8) mEq/kg/day and 0.9 (1.7) mEq/kg/day, respectively. The strongest independent predictor of sNaB in the cohort was urine output. In patients receiving HD, sNaB correlated with IDWG, pre-HD DBP, and first-hour refill index, a volume index based on blood volume monitoring. sNaB was the strongest predictor of IDWG in multiple regression analysis (ß = 0.63; p = 0.005). Neither SBP SDS nor DBP SDS correlated with sNaB. CONCLUSIONS: Na intake is higher than uNa in children on dialysis, and medications may be an important source of Na. sNaB is best predicted by urine output in the population, and it is a significant independent predictor of IDWG in children on HD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Expanding the Spectrum of Extracorporeal Strategies in Small Infants with Hyperammonemia.

Hyperammonemia is a life-threatening condition mainly due to the neurotoxicity of ammonia. Ammonia scavengers may be insufficient, and extracorporeal treatment may be required. Continuous treatments are preferred, and a high-dose continuous renal replacement therapy (CRRT) must be prescribed to ensure a fast ammonia depletion. Many of the children with hyperammonemia are newborns, with lower blood volume than older children. The majority of the CRRT systems are adult-based, with large extracorporeal priming volumes and inadequate UF control. Recent strides have been made in the development of CRRT systems more suitable for young children with smaller sets to use in adult machines and dedicated monitors for neonates and infants. The main advantage of the machines for adults is the higher dialysis fluid flows, however with greater hemodynamic risks. Pediatric monitors have been designed to reduce the extracorporeal volume and to increase the precision of the treatment. However, they have substantial limitation in clearance performances. In this review, we discuss on current strategies to provide CRRT in newborns and small infants with hyperammonemia. We also presented our experience with the use of CARPEDIEM™ implemented in a CVVHDF modality, boosting the diffusive clearance with a post-replacement convective mechanism.

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.

Acute paediatric kidney replacement therapies in Europe: demographic results from the EurAKId Registry.

BACKGROUND: Acute kidney injury (AKI), particularly that requiring dialysis, is a severe complication in hospitalized children that is associated with high morbidity and mortality. A prospective European AKI registry (EurAKId registry, NCT02960867) was created to describe the epidemiology and outcomes of paediatric patients treated with acute dialysis. METHODS: Children were recruited who were between 0 and 18 years of age and were treated both in and outside the paediatric intensive care unit (PICU) with peritoneal dialysis (PD), haemodialysis (HD) or continuous kidney replacement therapy (CKRT) for AKI or metabolic derangement, fluid overload (FO), sepsis or respiratory distress. Five age groups and 12 categories of primary diseases were defined. RESULTS: Data on 340 patients were analysed, of whom 86% received dialysis for AKI and 14% for reasons other than AKI. Boys accounted for 60% of the patients. Illness severity was greater in children with cardiac and haematologic diseases than those with kidney diseases. Most patients received dialysis in the PICU (84%). The most frequently used dialysis modality was CKRT (64%), followed by PD (14%) and HD (14%). The overall survival rate was 65%. Survival was significantly lower in children with three comorbidities than in children with no comorbidities (41% and 83%; P < 0.001). CONCLUSIONS: The EurAKId registry is the first prospective registry considering paediatric acute kidney replacement therapies (KRTs) in both critical and non-critical care settings, focusing on the three dialysis modalities in Europe. The clinical indications for KRT have expanded; our population was characterized by critically ill patients, primarily boys, who frequently received dialysis in the PICU with CKRT.

Survival of infants treated with CKRT: comparing adapted adult platforms with the Carpediem™.

BACKGROUND: The most severely ill neonates and infants with AKI who need kidney replacement therapy have had to rely upon peritoneal dialysis, or adaptations of veno-venous continuous kidney replacement therapy (CKRT) devices for adults. Data from the Prospective Pediatric CRRT (ppCRRT) registry observed children < 10 kg had a lower survival rate than children > 10 kg (44% vs. 64%, p < 0.001). A CKRT device designed specifically for small children could improve outcomes. The Cardio-Renal Pediatric Dialysis Emergency Machine (CARPEDIEM™) is specifically dedicated to providing CKRT for newborns and small infants. METHODS: We performed a retrospective cohort analysis comparing patient severity of illness and outcomes between the ppCRRT and CARPEDIEM registries, involving 6 Italian pediatric intensive care units. Thirty-eight subjects from the CARPEDIEM registry and 84 subjects from the ppCRRT registry < 10 kg were screened for comparison. We compared patient outcomes with a weight-matched cohort (< 5 kg) of 34 patients from the CARPEDIEM registry and 48 patients from the ppCRRT registry. RESULTS: The ppCRRT subjects had higher rates of vasoactive medication at CKRT initiation. Survival to CKRT termination was higher for CARPEDIEM subjects (33/34 vs. 21/48, p < 0.0001). Multivariable logistic regression showed that CARPEDIEM registry cohort was the only variable to retain an association with survival to CKRT discontinuation. CONCLUSIONS: We suggest children receiving CKRT using CARPEDIEM have excellent survival. Our data should be interpreted with caution given the retrospective comparison across two eras more than a decade apart.

How Covid-19 changed the epidemiology of febrile urinary tract infections in children in the emergency department during the first outbreak.

BACKGROUND: The first Covid-19 pandemic affected the epidemiology of several diseases. A general reduction in the emergency department (ED) accesses was observed during this period, both in adult and pediatric contexts. METHODS: This retrospective study was conducted on the behalf of the Italian Society of Pediatric Nephrology (SINePe) in 17 Italian pediatric EDs in March and April 2020, comparing them with data from the same periods in 2018 and 2019. The total number of pediatric (age 0-18 years) ED visits, the number of febrile urinary tract infection (UTI) diagnoses, and clinical and laboratory parameters were retrospectively collected. RESULTS: The total number of febrile UTI diagnoses was 339 (73 in 2020, 140 in 2019, and 126 in 2018). During the first Covid-19 pandemic, the total number of ED visits decreased by 75.1%, the total number of febrile UTI diagnoses by 45.1%, with an increase in the UTI diagnosis rate (+ 121.7%). The data collected revealed an increased rate of patients with two or more days of fever before admission (p = 0.02), a significant increase in hospitalization rate (+ 17.5%, p = 0.008) and also in values of C reactive protein (CRP) (p = 0.006). In 2020, intravenous antibiotics use was significantly higher than in 2018 and 2019 (+ 15%, p = 0.025). Urine cultures showed higher Pseudomonas aeruginosa and Enterococcus faecalis percentages and lower rates of Escherichia coli (p = 0.02). CONCLUSIONS: The first wave of the Covid-19 pandemic had an essential impact on managing febrile UTIs in the ED, causing an absolute reduction of cases referring to the ED but with higher clinical severity. Children with febrile UTI were more severely ill than the previous two years, probably due to delayed access caused by the fear of potential hospital-acquired Sars-Cov-2 infection. The possible increase in consequent kidney scarring in this population should be considered.

Extraperitoneal kidney transplantation: a comparison between children weighting ≤15 kg and >15 kg. Experience of a single institution.

Extraperitoneal approach is sometimes recommended for kidney transplantation (KT) in children weighting <15 kg. We hypothesized that this approach might be as successful as in patients with normal weight. Data of all consecutive KTs performed between 2013 and 2019 were retrospectively reviewed. Early outcomes and surgical complications were compared between children weighing ≤15 kg (low-weight (LW) group) and those weighing >15 kg (Normal-weight (NW) group). All the 108 KTs were performed through an extraperitoneal approach. The LW group included 31 patients (mean age 3.5 ± 1.4 years), whose mean weight was 11.1 ± 2.0 kg. In the LW group,-a primary graft nonfunction (PNGF) occurred in one patient (3.2%), surgical complications occurred in nine (29%), with four venous thrombosis. In the NW group, PNGF occurred in one case (1.3%), delayed graft function (DGF) in eight (10%), surgical complications in 11 (14%) with only one case of venous thrombosis. In both groups, no need for patch during wound closure and no wound dehiscence were reported. The extraperitoneal approach can be effectively used in LW children. No differences were observed in the overall complication rate (P = 0.10), except for the occurrence of venous thrombosis (P = 0.02). This might be related to patients' characteristics of the LW group.

Bench thrombolysis and "autotransplantation" as a rescue treatment for venous thrombosis after living-donor kidney transplantation.

BACKGROUND: Allograft venous thrombosis is a severe complication after kidney transplantation (KT). Early diagnosis and prompt treatment are crucial in preserving the survival of the allograft. In this study, we aimed to describe an emergent strategy for the management of acute allograft venous thrombosis. CASE PRESENTATION: A 4-year-old girl, weighing 13.5 kg, was diagnosed with bilateral congenital renal hypodysplasia, urogenital sinus and anorectal malformation. The patient was referred to our department for living-donor KT. Her mother was eligible as a donor, presenting a body weight ratio of 1:4.5. Thrombosis of the inferior vena cava (ICV) was also identified, without any predisposing factor for thrombophilia. KT was performed by an extraperitoneal approach without complications. Venous anastomosis required a human vascular graft sutured to the ICV, and renal artery was anastomosed to the aorta. On postoperative day (POD) 8, acute abdominal pain and hematuria led to the diagnosis of an allograft venous thrombosis. An emergent laparotomy was required to explant the allograft, followed by bench surgery. The allograft was irrigated with thrombolytic agents and lactated Ringer's solution and then after removing the venous vascular graft, it was reimplanted through vascular anastomosis with the ICV and aorta. The recovery of perfusion and function was good with diuresis since day 4 after re-surgery. At 2-year follow-up, the child presented normal allograft function with an estimated GFR of 65 ml/min/1.73 m2 . CONCLUSION: According to our experience, explantation of the kidney allograft, followed by irrigation with thrombolytics in bench surgery, and reimplantation resulted in unexpected optimal outcomes in the case of allograft venous thrombosis.

Growth in children on kidney replacement therapy: a review of data from patient registries.

Growth retardation is a major complication in children with chronic kidney disease (CKD) and on kidney replacement therapy (KRT). Conversely, better growth in childhood CKD is associated with an improvement in several hard morbidity-mortality endpoints. Data from pediatric international registries has demonstrated that improvements in the overall conservative management of CKD, the search for optimal dialysis, and advances in immunosuppression and kidney transplant techniques have led to a significant improvement of final height over time. Infancy still remains a critical period for adequate linear growth, and the loss of stature during the first years of life influences final height. Preliminary new original data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry confirm an association between the final height and the height attained at 2 years in children on KRT.

Returning to dialysis after kidney allograft failure: the experience of the Italian Registry of Paediatric Chronic Dialysis.

BACKGROUND: The need for dialysis after kidney allograft failure (DAGF) is among the top five reasons for dialysis initiation, making this an important topic in clinical nephrology. However, data are scarce on dialysis choice after transplantation and clinical outcomes for DAGF in children. METHODS: Patients receiving chronic dialysis < 18 years were recorded from January 1991 to January 2019 by the Italian Registry of Pediatric Chronic Dialysis (IRPCD). We investigated factors influencing choice of dialysis modality, patient outcome in terms of mortality, switching dialysis modality, and kidney transplantation. RESULTS: Among 118 patients receiving DAGF, 41 (35%) were treated with peritoneal dialysis (PD), and 77 (65%) with haemodialysis (HD). Significant predictors for treatment with PD were younger age at dialysis start (OR 0.85 per year increase [95%CI 0.72-1.00]) and PD use before kidney transplantation (OR 8.20 [95%CI 1.82-37.01]). Patients entering DAGF in more recent eras (OR 0.87 per year increase [95%CI 0.80-0.94]) and with more than one dialysis modality before kidney transplantation (OR 0.56 for being treated with PD [0.12-2.59]) were more likely to be initiated on HD. As compared to patients on HD, those treated with PD exhibited increased but non-significant mortality risk (HR 2.15 [95%CI 0.54-8.6]; p = 0.28) and higher prevalence of dialysis-related complications during DAGF (p = 0.002) CONCLUSIONS: Patients entering DAGF in more recent years are more likely to be initiated on HD. In this specific population of children, use of PD seems associated with a more complicated course. A higher resolution version of the Graphical abstract is available as Supplementary information.

Oral steroids for reducing kidney scarring in young children with febrile urinary tract infections: the contribution of Bayesian analysis to a randomized trial not reaching its intended sample size.

BACKGROUND: This study aimed to evaluate the effect of oral dexamethasone in reducing kidney scars in infants with a first febrile urinary tract infection (UTI). METHODS: Children aged between 2 and 24 months with their first presumed UTI, at high risk for kidney scarring based on procalcitonin levels (≥1 ng/mL), were randomly assigned to receive dexamethasone in addition to routine care or routine care only. Kidney scars were identified by kidney scan at 6 months after initial UTI. Projections of enrollment and follow-up completion showed that the intended sample size could not be reached before funding and time to complete the study ran out. An amendment to the protocol was approved to conduct a Bayesian analysis. RESULTS: We randomized 48 children, of whom 42 had a UTI and 18 had outcome kidney scans (instead of 128 planned). Kidney scars were found in 0/7 and 2/11 patients in the treatment and control groups respectively. The probability that dexamethasone could prevent kidney scarring was 99% in the setting of an informative prior probability distribution (which fully incorporated in the final inference the information on treatment effect provided by previous studies) and 98% in the low-informative scenario (which discounted the prior literature information by 50%). The probabilities that dexamethasone could reduce kidney scar formation by up to 20% were 61% and 53% in the informative and low-informative scenario, respectively. CONCLUSIONS: Dexamethasone is highly likely to reduce kidney scarring, with a more than 50% probability to reduce kidney scars by up to 20%. TRIAL REGISTRATION NUMBER: EudraCT number: 2013-000388-10; registered in 2013 (prospectively registered) A higher resolution version of the Graphical abstract is available as Supplementary information.

Ten-year trends in epidemiology and outcomes of pediatric kidney replacement therapy in Europe: data from the ESPN/ERA-EDTA Registry.

BACKGROUND: For 10 consecutive years, the ESPN/ERA-EDTA Registry has included data on children with stage 5 chronic kidney disease (CKD 5) receiving kidney replacement therapy (KRT) in Europe. We examined trends in incidence and prevalence of KRT and patient survival. METHODS: We included all children aged <15 years starting KRT 2007-2016 in 22 European countries participating in the ESPN/ERA-EDTA Registry since 2007. General population statistics were derived from Eurostat. Incidence and prevalence were expressed per million age-related population (pmarp) and time trends studied with JoinPoint regression. We analyzed survival trends using Cox regression. RESULTS: Incidence of children commencing KRT <15 years remained stable over the study period, varying between 5.5 and 6.6 pmarp. Incidence by treatment modality was unchanged over time: 2.0 for hemodialysis (HD) and peritoneal dialysis (PD) and 1.0 for transplantation. Prevalence increased in all age categories and overall rose 2% annually from 26.4 pmarp in 2007 to 32.1 pmarp in 2016. Kidney transplantation prevalence increased 5.1% annually 2007-2009, followed by 1.5% increase/year until 2016. Prevalence of PD steadily increased 1.4% per year over the entire period, and HD prevalence started increasing 6.1% per year from 2011 onwards. Five-year unadjusted patient survival on KRT was around 94% and similar for those initiating KRT 2007-2009 or 2010-2012 (adjusted HR: 0.98, 95% CI:0.71-1.35). CONCLUSIONS: We found a stable incidence and increasing prevalence of European children on KRT 2007-2016. Five-year patient survival was good and was unchanged over time. These data can inform patients and healthcare providers and aid health policy makers on future resource planning of pediatric KRT in Europe.

Resident foreign patients receive adequate dialysis but fewer preemptive transplantations: data from the Italian pediatric dialysis registry.

BACKGROUND: Sociocultural issues play a key role in children needing kidney replacement therapy (KRT). METHODS: Data of incident patients < 18 years treated with chronic dialysis or preemptive kidney transplantation (pTx) between 2007 and 2016 were retrospectively collected from the Italian Pediatric Dialysis Registry; KRT modality and outcome were compared between patients with at least one non-Italian parent ("resident foreign patients," RFPs) and those from native parents ("domestic patients," DPs) and between the quinquennium 2007-2011 (period 1) and 2012-2016 (period 2). RESULTS: We included 448 children (26.8% RFPs). The percentage of RFPs increased from 23 to 30.3% (p = 0.08) from periods 1 to 2. They were younger (6.7 vs. 9.4 years, p = 0.025) and less often treated with pTx (3.3 vs. 13.4%, p = 0.009) than DPs. The percentage of pTx increased from period 1 to 2 in RFPs only (8.4-18.6%, p = 0.006). Independent predictors of a lower probability of pTx were lower age, belonging to RFPs group, starting KRT in period 1 and focal segmental glomerulosclerosis or glomerulopathy as primary kidney disease. Peritoneal dialysis was the preferred dialysis modality in both groups. Age, primary kidney disease, and center size were independently associated with dialysis modality choice. Patient survival, waiting time to Tx, and dialysis modality survival were not different between the two groups. CONCLUSIONS: The proportion of patients receiving KRT born from immigrant families increased in recent years in Italy. They were younger and less often treated with pTx than domestic patients. In case of dialysis, the outcome was not different between the two groups. Graphical abstract.

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.