KEY POINTS:Among 72 patients with childhood-onset ANCA-associated vasculitis, kidney transplant survival was good (86%). ANCA-associated vasculitis relapse occurred in 8 patients (11%), a median of 71 months after transplantation and resulted in graft failure in only one case. Positive ANCA at the time of transplantation did not predict graft failure but was associated with a higher risk of relapse and worse graft function. BACKGROUND:ANCA-associated vasculitis (AAV) is rare in children, and results in kidney failure in up to one third of cases. There is very limited knowledge on kidney transplantation in childhood-onset AAV. We assessed kidney transplantation outcomes and prognostic factors in a multicenter cohort of patients with childhood-onset AAV. METHODS:Patients diagnosed with AAV during childhood (≤18 years) who received a kidney transplant were included in this retrospective study. We determined patient and graft survival, rates of chronic graft dysfunction (defined as eGFR <60 ml/min per 1.73 m 2 for ≥3 months) and AAV relapse, and assessed determinants of outcome with logistic regression models. Patients were matched 1:2 for age, sex, and era of transplantation with non-AAV recipients from the Hospital for Sick Children in Toronto, Canada, and their graft survival was compared. RESULTS:We included 72 patients, of whom 53 (74%) had microscopic polyangiitis and 19 (26%) granulomatosis with polyangiitis. Their median age (interquartile range at the time of diagnosis and transplantation was 12 (9-14) and 14 (12-16) years, respectively. After a median post-transplant follow-up of 53 months (interquartile range, 25-97), 70 patients (97%) were alive, 62 (86%) had a functioning graft, 28 (39%) had developed chronic graft dysfunction, and 8 (11%) had experienced AAV relapse. Graft survival was comparable between AAV and non-AAV recipients. Acute rejection was the only independent predictor of graft failure (hazard ratio [HR], 12.11; 95% confidence interval [CI], 1.19 to 122.49). Positive ANCA at the time of transplantation was significantly associated with a chronic graft dysfunction (HR, 4.16; 95% CI, 1.71 to 10.13) and AAV relapse (HR, 23.1; 95% CI, 2.67 to 200.28). CONCLUSIONS:Patients with childhood-onset AAV show good overall and graft survival after kidney transplantation and a low rate of post-transplant relapse. Further studies are warranted to confirm whether positive ANCA at the time of transplantation is associated with poorer graft outcomes.

Key Points Among 72 patients with childhood-onset ANCA-associated vasculitis, kidney transplant survival was good (86%). ANCA-associated vasculitis relapse occurred in 8 patients (11%), a median of 71 months after transplantation and resulted in graft failure in only one case. Positive ANCA at the time of transplantation did not predict graft failure but was associated with a higher risk of relapse and worse graft function. Background ANCA-associated vasculitis (AAV) is rare in children, and results in kidney failure in up to one third of cases. There is very limited knowledge on kidney transplantation in childhood-onset AAV. We assessed kidney transplantation outcomes and prognostic factors in a multicenter cohort of patients with childhood-onset AAV. Methods Patients diagnosed with AAV during childhood (≤18 years) who received a kidney transplant were included in this retrospective study. We determined patient and graft survival, rates of chronic graft dysfunction (defined as eGFR <60 ml/min per 1.73 m 2 for ≥3 months) and AAV relapse, and assessed determinants of outcome with logistic regression models. Patients were matched 1:2 for age, sex, and era of transplantation with non-AAV recipients from the Hospital for Sick Children in Toronto, Canada, and their graft survival was compared. Results We included 72 patients, of whom 53 (74%) had microscopic polyangiitis and 19 (26%) granulomatosis with polyangiitis. Their median age (interquartile range at the time of diagnosis and transplantation was 12 (9–14) and 14 (12–16) years, respectively. After a median post-transplant follow-up of 53 months (interquartile range, 25–97), 70 patients (97%) were alive, 62 (86%) had a functioning graft, 28 (39%) had developed chronic graft dysfunction, and 8 (11%) had experienced AAV relapse. Graft survival was comparable between AAV and non-AAV recipients. Acute rejection was the only independent predictor of graft failure (hazard ratio [HR], 12.11; 95% confidence interval [CI], 1.19 to 122.49). Positive ANCA at the time of transplantation was significantly associated with a chronic graft dysfunction (HR, 4.16; 95% CI, 1.71 to 10.13) and AAV relapse (HR, 23.1; 95% CI, 2.67 to 200.28). Conclusions Patients with childhood-onset AAV show good overall and graft survival after kidney transplantation and a low rate of post-transplant relapse. Further studies are warranted to confirm whether positive ANCA at the time of transplantation is associated with poorer graft outcomes.

BACKGROUND:Continuous kidney replacement therapy (CKRT) has emerged as a valuable treatment option in critically ill neonates and infants with acute kidney injury (AKI) requiring dialysis. In this population, we apply artificial intelligence (AI) to identify factors influencing mortality and short-term adverse kidney outcomes. METHODS:The study involved neonates and infants included in the EurAKId Registry (NCT02960867), who underwent CKRT treatment. Using the AI XGBoost models, we identified key clinical factors associated with short-term outcomes: mortality before hospital discharge, as well as proteinuria at discharge. We considered the patients' clinical characteristics, anthropometric features, and CKRT technical settings. RESULTS:The study comprised 95 patients: 31.6% neonates and 68.4% infants with a median age at hospital admission of 1 month (interquartile range, IQR 0-7 months). Ten children were born prematurely. The overall mortality rate was 47.3% and did not differ significantly between neonates and infants (53.3% vs 44.4%, respectively, P = .422). The XGBoost model for predicting mortality had the accuracy of 59.53% ± 0.96% and AUC of 0.64 ± 0.11. Lower urine output at CKRT initiation, a greater rise in serum creatinine (SCr), longer time to dialysis initiation, and lower blood pressure were associated with increased risk of mortality. Proteinuria at hospital discharge was present in 30.6% of survivors. The XGBoost model for predicting proteinuria had the accuracy of 79.11% ± 2.46% and AUC (0.74 ± 0.04). Higher SCr concentrations at hospital admission and at CKRT start, as well as primary kidney disease were the most important risk factors for proteinuria. CONCLUSION:We propose the XGBoost models for identifying factors associated with short-term outcomes of CKRT in neonates and infants. Lower urine output at CKRT start, more severe AKI progression and longer time to CKRT initiation might be important risk factors for mortality in infants and neonates. Primary kidney disease and related biochemical parameters are strong predictors of proteinuria at hospital discharge.

The choice of vascular access (VA) plays a key role in the success of hemodialysis (HD). Despite their widespread use, central venous catheters (CVCs) are associated with higher rates of dysfunction, thrombosis, and catheter-related bloodstream infections (CRBSI). We investigated current practices in pediatric HD across European pediatric nephrology centers, focusing on VA choices, infection control measures, and CRBSI management. An online questionnaire was e-mailed to 119 members of the European Society for Pediatric Nephrology (ESPN) Dialysis Working Group and European Pediatric Dialysis Working Group (EPDWG). Descriptive statistics were used to summarize practices across centers, comparative analyses between centers in countries with Human Development Index (HDI) > 0.90 and < 0.90. Thirty-one centers across Europe participated in the survey. CVCs were the primary VA in 73.1

Objectives: Children may present with acute kidney injury (AKI) and polyuria under certain conditions which can complicate diagnosis and management. This review seeks to synthesize AKI presentations in children with polyuria. Methods: Publications for this systematic review were searched using Embase, PubMed, and Scopus. Methodological quality assessment of the included study and case reports was performed. Results: From the selected studies, we obtained data on 32 patients with a mean age of 11.02 ± 2.82 years, including 13 males and 19 females. Among them, 26 presented with polyuria: 19 with diabetic ketoacidosis (DKA), 5 with new-onset type 1 diabetes mellitus (T1DM) without DKA, 1 with Bartter syndrome, and 1 with neuroblastoma. In 12 patients with DKA, data to calculate AKI prevalence were not available. Among the remaining 20 patients (all with polyuria), 9 (45%) developed AKI. AKI stage 3 was observed in 4 patients and stage 2 in 1 patient. For the remaining 5 patients with AKI, no information about the AKI stage was available. Conclusions: AKI can present with polyuria as part of its pathophysiological mechanism. A relationship between polyuria and AKI (with KDIGO stage ≥ 2) was found in metabolic disorders (DKA), nephrological diseases (Bartter syndrome), and oncological conditions (neuroblastoma).

Children receiving kidney replacement therapy frequently face complications resulting in recurrent hospitalizations. This nationwide retrospective observational study, conducted using data from the Italian Registry of Pediatric Chronic Dialysis (IRPCD), aimed to compare hospitalization rates and causes between children treated with chronic peritoneal dialysis (PD) and hemodialysis (HD). The study included children (< 18 years) on chronic PD or HD recorded between January 2000 and December 2019. Hospitalizations were defined as admissions involving at least one overnight stay, excluding those for dialysis initiation or kidney transplantation. Hospitalization causes were categorized as infectious and non-infectious dialysis-related complications, other infections, non-infectious conditions, diagnostic procedures, and complications related to kidney failure. A total of 847 dialysis patients (493 on PD, 354 on HD) were included. Among 813 patients, 420 (51.7

INTRODUCTION:Hypothermic machine perfusion currently represents the gold standard preservation modality for kidneys retrieved from adult deceased donors, with reduced delayed graft function (DGF) rates and improved early transplant survival compared to static cold storage (SCS). To date, clinical experience with hypothermic oxygenated machine perfusion (HOPE) in pediatric kidney transplants (KT) setting remains extremely limited. METHODS:We conducted a single-center retrospective analysis of pediatric KT recipients preserved using HOPE. Between November 2019 and December 2023, 129 pediatric kidney transplants were performed at our institution. After exclusion of living donor transplants (n = 37), 92 recipients were included: 40 grafts preserved using HOPE and 52 using SCS. Clinical outcomes, graft function, and survival were compared between groups. RESULTS:The study cohort consisted mainly of male (59.8%), with a mean recipient age of 12.6 ± 5.9 years. Baseline donor and recipient characteristics were comparable between groups. Despite a significantly longer total cold preservation time (CPT) in the HOPE group (23.7 ± 4.1 vs. 13.3 ± 3.7 h; p < 0.001), no significant differences were observed in the incidence of DGF, biopsy-proven acute rejection, postoperative length of stay, or graft function up to 1 year. One-year death-censored graft survival was 97% in the HOPE group and 98% in the SCS group, with no significant difference between preservation strategies. CONCLUSION:In this first clinical experience with HOPE in pediatric KT, oxygenated hypothermic perfusion proved to be safe and feasible, even in the setting of prolonged CPT. The implementation of HOPE programs could improve the logistical management of pediatric donors and recipients without compromising transplant results.

The medical management of failing kidney allografts is poorly understood even in adult patients with wide variations in practice. We studied failing kidney allografts in European children and provided insights into their management, including cardiovascular, CKD management, and changes to immunosuppression. A 3-year (2020–2023) retrospective study of current practices in the management of children with failing kidney allografts (with at least 1 year of follow-up) was conducted. A failing kidney allograft was defined as an eGFR < 30 mL/min/1.73 m2 for 3 consecutive months, as agreed through an iterative Delphi process. All children who had a kidney transplant performed at < 18 years of age with a failing kidney allograft were included. Data were collected through the CERTAIN (Cooperative European Pediatric Renal Transplant Initiative) registry. Pearson correlation and Spearman’s rank were used for continuous variables. Multivariate Cox proportional hazards models estimated associations of exposure with outcome. All statistical analyses were performed using Stata Version 16.0. A total of 119 patients from 27 European centres were included. At the time of allograft failure, 76

BackgroundBlood purification techniques are rarely used in low-weight pediatric patients because extracorporeal circuits and devices designed for adults may expose neonates and infants to significant adverse events. Recently, hemoadsorption cartridges with low priming volumes (Jafron®) have become available.Case descriptionWe report a descriptive case series of four pediatric patients treated with hemoadsorption using HA60 cartridges, including two neonates (2.8 kg and 3.5 kg) and two infants (7 kg and 10 kg). All patients were admitted to the PICU with septic shock and received standard therapy, including broad-spectrum antibiotics and vasoactive agents. Two of the four patients required extracorporeal membrane oxygenation (ECMO) because of severe respiratory and circulatory failure. In all patients, continuous renal replacement therapy (CRRT) was initiated for acute kidney injury and/or fluid overload, and HA60 hemoadsorption was added. Clinical and laboratory parameters, together with vasoactive drug requirements, were recorded from the initiation of hemoadsorption until the end of treatment. Three of the four patients survived.Discussion and conclusionsOur findings are limited to describing the feasibility and safety of HA60 hemoadsorption in neonates and small infants with septic shock, as well as the logistical aspects associated with the use of these novel extracorporeal technologies, rather than demonstrating clinical efficacy. No major adverse events were observed. Within this perspective, the fatal outcome observed in Case 1 was considered unrelated to the hemoadsorption procedure itself. Given the descriptive nature of the study and the presence of multiple concomitant therapies, no conclusions regarding efficacy can be drawn. Larger studies are needed to confirm these preliminary observations.

Introduction CytoSorb® is a cartridge for the adsorption of inflammatory mediators, bilirubin, myoglobin and other xenobiotics, directly from the blood stream. Clinical experience is widely documented in adults, whereas, in the paediatric settings, it is currently limited to single case reports or monocentric studies. In order to be able to collect evidence in larger paediatric populations, an Italian multicentre network (CYTOPED study group) was founded. Methods Italian multicentric observational registry on the use of CytoSorb® in critically ill paediatric patients. Prospective enrolment by Italian Children’s Hospitals has been ongoing since February 2021 with a retrospective analysis conducted from February 2018 to February 2021. Results 62 patients have been enrolled. Median Paediatric Logistic Organ Dysfunction 2 (PELOD-2) score on Paediatric Intensive Care Unit (PICU) admission was 7 (IQR 4;10). The primary clinical indications for haemoadsorption (HA) were sepsis or septic shock (n = 36), followed by liver failure, rhabdomyolysis, cardiac surgery. CytoSorb® has been applied in 87% of cases integrated in a continuous renal replacement therapy (CRRT) circuit. The median time of HA was 48 h (IQR 26;72) and the median number of cartridges used was 2 (IQR 1;3). Anticoagulation in the extracorporeal circuit has been managed with heparin (76%) and regional citrate anticoagulation (24%). Adverse events were recorded in 12 patients. Conclusion Our data provide some insights into safety and feasibility of CytoSorb® therapy in children. The advancement of the study and the prospective arm of CYTOPED registry will allow further investigation into this therapy, including dosage, timing and use of antibiotics in conjunction with extracorporeal blood purification techniques.

BACKGROUND:Haemoadsorption (HA) is increasingly recognized as a valuable extracorporeal blood purification technique in paediatric intensive care. Although initially developed for adult patients, HA's application in paediatric critical care, particularly for conditions such as septic shock, liver failure, and rhabdomyolysis, has gained significant attention due to promising clinical outcomes. SUMMARY:HA has demonstrated efficacy in managing paediatric septic shock by reducing vasopressor requirements and lowering inflammatory markers. In liver failure, HA complements continuous renal replacement therapy (CRRT) by removing albumin-bound toxins and cytokines, mitigating systemic inflammation. Emerging evidence also supports HA as a rescue therapy in rare paediatric conditions like rhabdomyolysis and acute intoxications, preventing organ damage and reducing morbidity. Despite its benefits, HA in paediatrics presents technical challenges, including concerns over extracorporeal circuit volumes, vascular access, and anticoagulation. Paediatric-specific devices, such as the HA60, BS80, and PMX-05R, are addressing these limitations by offering lower priming volumes suitable for small children. Recent studies have highlighted improvements in haemodynamic stability, cytokine reduction, and organ function, reinforcing HA's potential as a critical adjuvant therapy. This review underscores the evolving landscape of HA in paediatric critical care, advocating for further research to optimize its application across diverse clinical scenarios. KEY MESSAGES:(1) HA shows significant promise in paediatric septic shock, liver failure, and rhabdomyolysis. (2) Technical advancements are expanding HAs applicability to neonates and small infants. (3) More multicentre studies are needed to establish HA's role in reducing mortality and improving quality of life post-PICU.

Cardiac Surgery-associated acute kidney injury (CS-AKI) is a common complication in children. Comparison of studies over the last 2 decades has been difficult because of varying definitions and practice heterogeneity. Multiple risk factors exist; however, few are modifiable. Limitations in serum creatinine and urine output have hampered precision in CS-AKI diagnosis. Delineating CS-AKI using durational, biomarker-based, and fluid sub-phenotypes has strengthened associations with outcomes. Despite the significant short and long-term effects of CS-AKI, no study has proven efficacious for its prevention or treatment. Targeted early risk stratification tools should be considered for prognostication and possible clinical trial enrichment. Long-term consequences of CS-AKI need further study, given the inconsistency in findings, through systematic follow-up of these high-risk patients.

Background:Limited data exist on rehospitalization in paediatric dialysis patients. The objective of this study was to identify indications, rates and risk factors for 30-day readmissions in this population. Methods:We used a prospective multinational, multicentre cohort study of haemodialysis (HD) and peritoneal dialysis (PD) patients discharged between July 2017 and July 2018. Readmission was identified as repeat hospitalization within 30 days of a prior (index) admission. Potentially preventable readmissions were clinically related to the initial admission. Early readmissions were those occurring within 7 days of discharge. The primary outcome was 30-day readmission. Secondary outcomes included potentially avoidable and early readmissions. Results:A total of 54 (31%) of 176 patients (102 PD, 74 HD) had at least one readmission; 84 (18%) discharges were followed by readmission. PD and HD patients had similar readmission rates {30.4% versus 31.1%; hazard ratio [HR] 1.06 [95% confidence interval (CI) 0.61-1.81]}. Compared with PD, HD patients had a significantly shorter time to readmission (8 versus 14 days; P = .019), higher early readmission rates (46% versus 18%; P = .010) and risk [odds ratio (OR) 3.87 (95% CI 1.35-11.11)]. Main readmission causes were dialysis access-related non-infectious complications (31%) and access infections (22.7%); 47% of readmissions were potentially avoidable. Lower haemoglobin levels were linked to readmission [HR 0.78 (95% CI 0.64-0.95)]. Bicarbonate use was associated with a 51% lower readmission risk [HR 0.49 (95% CI 0.24-0.99)]. Neurological comorbidity [OR 7.00 (95% CI 1.04-47.22)] and partial recovery [OR 56.45 (95% CI 3.02-1053.10)] were risk factors for avoidable readmission. Risk of avoidable and early readmission decreased with age [OR 0.98 (95% CI 0.97-0.99) and OR 0.99(95%CI 0.98-0.99), respectively]. Conclusions:Readmissions are common in paediatric dialysis patients, with a substantial proportion being potentially preventable. To reduce rehospitalizations, interventions should target modifiable factors such as access complications, anaemia and incomplete recovery at discharge, while recognizing non-modifiable risks like HD and younger age to identify high-risk patients.

We investigated factors associated with post-transplant growth in pediatric kidney transplant (KTx) recipients with a focus on plasma bicarbonate (HCO3−) and estimated the effect of alkali treatment on growth. In this study of the CERTAIN Registry, data were collected up to 5 years post-transplant. Generalized Additive Mixed Models were applied to assess the association between post-transplant growth and covariates. A trial-emulation analysis was performed to estimate the causal effect of alkali supplementation on growth. We report on 2147 primary KTx recipients with a median age at KTx of 10.2 (IQR 5.1;14.3) years. No statistically significant association was found between growth and HCO3− (p = 0.21), but the shape of the estimated conditional association showed a decreasing estimated growth with increasing HCO3−. Glucocorticoid treatment and allograft rejection showed an inverse association with growth. Living donor KTx, glomerulopathy, recombinant growth hormone use, low height z-score at KTx, younger age, and higher eGFR were positively associated with growth. The trial-emulation analysis included patients at 30 days and 3, 6, and 9 months post-transplant with HCO3− < 22 mmol/L and no prior alkaline treatment. Alkaline treatment was initiated in 194, 93, 47, and 25 patients, respectively. After adjustment for confounders, there was no significant difference in growth at 1-year post-transplant in treated and untreated patients. We found no association between HCO3− and growth nor evidence of improved growth after treatment of metabolic acidosis. Living donor KTx was positively associated with post-transplant growth, while there was an inverse association with allograft rejection.

High panel reactive antibody (PRA) titers are a significant challenge for patients undergoing kidney transplantation. Currently, no desensitization protocol has proven effective in preventing mid- and long-term graft loss. In the present study, we used anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in an attempt to reduce PRA in a highly sensitized patient. The role of this therapy in preventing focal segmental glomerulosclerosis (FSGS) recurrence was also evaluated. An 18-year-old girl with primary kidney failure secondary to FSGS failed a first kidney transplant at age 4 years due to disease recurrence. Despite being listed in a special program for hyperimmune patients, she had not been offered a new kidney. She received a single infusion of anti-CD19 CAR T cells after lymphodepletion therapy. Anti-human leukocyte antigens (HLA) antibody titers were monitored before therapy and monthly thereafter. PRA titers decreased progressively during the first 6 months after CAR T-cell therapy. Unexpectedly, after 5.5 months, the patient was offered a cadaveric kidney that was fully matched for HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ at the antigen level. However, she developed an early relapse of FSGS for which she started plasmapheresis, which prevented further monitoring of PRA titers. This case shows that a single infusion of anti-CD19 CAR T cells can induce a durable reduction of anti-HLA antibodies in highly sensitized patients. However, profound B-cell depletion did not prevent FSGS relapse.