Acute kidney injury (AKI) is common among neonates in the intensive care unit and has been linked to abnormal neurodevelopment, yet long-term effects on brain structure remain uncharacterized. In this secondary analysis, we compared brain white matter integrity, measured by fractional anisotropy (FA) on 3T MRI, in children ages 5-12 years born preterm with (n=5) versus without (n=10) a history of neonatal AKI. Contrary to our hypothesis, children with prior neonatal AKI showed higher FA across seven white matter regions in unadjusted analyses. After adjustment for sex, birth weight, and age at MRI, the AKI group retained significantly greater FA in the corticospinal tract (β=0.7, 95% CI 0.09-1.31) and superior frontooccipital fasciculus (β=0.68, 95% CI 0.02-1.34). Because elevated FA may reflect compensatory glial responses rather than improved neurological function, these findings suggest neonatal AKI may have lasting, complex effects on white matter microstructure. Larger studies pairing neuroimaging with neurocognitive assessment are needed.

Biological sex plays a crucial role in the pathophysiology of morbidities related to preterm birth. Studies specifically investigating the role of biological sex in neonatal kidney disease are lacking. This study aimed to determine the association between biological sex and kidney outcomes in preterm infants. We hypothesized that male infants would be more likely to have poor kidney outcomes, including acute kidney injury (AKI), hypertension and chronic kidney disease. Given data on the relationship between sex, AKI and lung disease, we also evaluated lung disease as a secondary outcome. Retrospective analysis of the Preterm Erythropoietin Neuroprotection Trial data. For adjusted models, we used covariates associated with adverse outcomes a priori (gestational age, SGA status) and a lasso regression. AKI was defined using creatinine only neonatal modified KDIGO criteria and bronchopulmonary dysplasia (BPD) by Neonatal Research Network criteria. Of the 923 infants included, 479 (51.8

KEY POINTS:Early trial of liberation from continuous renal replacement therapy was associated with improved patient-important clinical outcomes in children with preserved urine output. Hierarchical composite end point analysis demonstrated greater intensive care unit and hospital-free days among patients who underwent a liberation trial. These findings supported early assessment of readiness for liberation using urine output to guide decision making for children receiving continuous renal replacement therapy. BACKGROUND:Data to guide assessment of readiness for liberation from continuous renal replacement therapy (CRRT) in children are limited, and hierarchical composite end points have not been applied in this setting. We evaluated whether performing a trial of CRRT liberation among patients with preserved urine output is associated with improved outcomes using a hierarchical end point approach. METHODS:We conducted a retrospective cohort study of patients aged≤25 years from the multicenter Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease registry. Patients with urine output >0.5 ml/kg per hour for≥24 hours within the first 5 days after CRRT initiation were included. The primary exposure was a trial of CRRT liberation by day 5. The primary outcome was a hierarchical composite of: ( 1 ) 90-day mortality, ( 2 ) 90-day KRT dependence, ( 3 ) intensive care unit-free days, and ( 4 ) hospital-free days. Inverse probability weighting was used to balance baseline characteristics, and outcomes were compared using a win ratio analysis. RESULTS:Among 366 eligible patients, 192 (53%) underwent a liberation trial by day 5. These patients were older, had higher reference serum creatinine levels, and exhibited lower illness severity when compared with those who did not undergo a trial of liberation. In adjusted analyses, a liberation trial was associated with an improved hierarchical outcome (win ratio, 2.14 [95% confidence interval, 1.56 to 2.94], P < 0.001), driven primarily by greater intensive care unit- and hospital-free days. CONCLUSION:Among CRRT recipients with preserved urine output, a trial of liberation by day 5 was associated with improved outcomes, supporting the early assessment of liberation readiness in patients with a urine output >0.5 ml/kg per hour.

The prospective pediatric Continuous Renal Replacement Therapy (ppCRRT) registry identified the degree of fluid accumulation (FA) at continuous kidney replacement therapy (CKRT) initiation as a predictor of adverse outcomes in children. These predate major advancements in CKRT technology and fluid stewardship. We aimed to describe the epidemiology of FA at CKRT initiation and associated outcomes in a contemporary paediatric cohort. Secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), a retrospective, multicenter study (35 centers, 9 countries) of patients ≤ 25 years treated with CKRT from 2015 to 2021. Primary Outcome: survival to ICU discharge. Secondary outcomes: ventilator-free and ICU-free days. A total of 1027 patients were included in this analysis. Survival to ICU discharge was 64.5

Idiopathic nephrotic syndrome (INS) is a podocyte disease triggered by immune-derived factors. Endothelial activation occurs in this context, but whether the activated endothelium contributes to podocyte injury is unknown. We tested the hypothesis that CD93, a protein primarily expressed in the endothelium, is a contributory factor of podocyte injury. We studied 460 patients with INS and 150 with other podocytopathies. CD93 was analyzed in kidney tissue, urine, and serum samples. We tested the efficacy of CD93 blockade in vitro and in vivo and investigated the relationship between soluble CD93 and clinical outcomes in human INS. CD93 was highly expressed by glomerular endothelial cells (GEnCs) in human INS, and INS sera stimulated cultured human GEnCs to release CD93. Mechanistically, soluble CD93 mediated podocyte activation via β1 integrin/FAK signaling in cultured human podocytes. CD93 blockade mitigated the activation of cultured human podocytes and albumin permeability in human GEnC-podocyte cocultures as well as albuminuria, glomerulosclerosis, and podocyte loss in two models of nephrotic syndrome: podocyte-specific transforming growth factor-β1 signaling (PodTgfbr1) mice and adriamycin-treated mice. Cd93 knockout mice showed less proteinuria and glomerulosclerosis, compared with controls, after adriamycin injection. In patients with INS, soluble CD93 was high in urine in ~90% and 50% of patients in relapse and remission, respectively. High urinary CD93 was associated with faster decline in kidney function and slower response to immunosuppression. Soluble and glomerular CD93 was also elevated in other podocytopathies. We conclude that soluble CD93 contributes to podocyte injury.

Acute kidney injury (AKI) and fluid accumulation (FA) are common during extracorporeal membrane oxygenation (ECMO) support and are associated with increased morbidity and mortality. Despite their clinical importance, contemporary data describing the epidemiology and management of these conditions remain limited. Founded in 2021, the Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) seeks to improve outcomes for children requiring extracorporeal organ support. This report describes the design of the WE-ROCK ECMO study, an international, multicenter, retrospective cohort of patients supported with ECMO from 2018 to 2022. We include 1,264 children aged 0-25 years treated at 43 centers across 10 countries. Collected data include demographics, clinical characteristics before ECMO initiation, and detailed information from the first 14 days of ECMO support, including fluid intake and output, diuretic use, and continuous renal replacement therapy (CRRT) practices. Primary outcomes include major adverse kidney events at 90 days (mortality, dialysis dependence, and persistent kidney dysfunction) as well as functional status outcomes. The WE-ROCK ECMO study represents the largest international investigation of kidney and fluid-related variables in pediatric ECMO, providing critical insight into practice variation and the relationships among AKI, FA, CRRT, and clinical outcomes, and establishing a foundation for future interventional trials.

Acute kidney injury (AKI) is a common condition globally associated with substantial morbidity, mortality and costs to health-care systems. The epidemiology and outcomes of AKI differ within and between countries, and depend on multiple factors. Social determinants of health (SDoHs) are the circumstances in which people are born, grow, work, live and age, including the broader set of forces and systems that influence the conditions of everyday life. Despite advances in medical care, many inequities, including those associated with socioeconomic status, race, ethnicity, gender and environment, persist and are increasingly recognized to influence health outcomes. Superimposed on these inequities are differences in access to health care and health resources, including public health prevention, access to screening, early diagnosis and treatment (including kidney replacement therapy), and quality of care, which vary within and between high- and low-resource settings. Over the past few years, these disparities have intensified as societies have emerged from a global pandemic and are challenged with accelerating climate change and escalating levels of global conflict. However, the role of SDoHs remains poorly defined for people with or at risk of AKI. Targeted policies addressing SDoHs are essential to reduce AKI burden globally. Here, we examine the effects of SDoHs on the incidence, recognition, management, follow-up and outcomes of adult and paediatric populations at risk of or with AKI.

Introduction: The lack of peritoneal dialysis (PD) catheters designed explicitly for neonates creates significant challenges in the provision of neonatal PD. High resource settings can circumvent this limitation by resorting to alternative extracorporeal dialysis methods. However, in low-resource settings, PD remains the preferred dialysis modality, and the use of off-label catheters for PD results in complications such as omental wrapping and occlusion. This study introduces a novel catheter design featuring a multi-diameter side port configuration and a helical geometry. Methods: We employed numerical simulations to identify an optimal multi-diameter side port configuration, to address fluid dynamic issues that lead to catheter occlusion and omental wrapping. Following the simulations, we experimentally evaluated the catheter's performance in a series of benchtop tests designed to simulate physiological conditions encountered in neonatal PD. Results: Our experimental evaluations demonstrated that the helical catheter outperforms commonly utilized pigtail catheters with same-sized diameter side ports by consistently achieving superior drainage efficiency during fibrin clot occlusion and omental wrapping tests. Conclusion: The catheter is intended to be placed at the bedside to perform renal replacement therapy for neonates in low-resourced settings. (c) 2025 The Author(s). Published by S. Karger AG, Basel

Acute kidney injury (AKI) occurs commonly in critically ill children. The impact of AKI on pediatric growth outcomes has been sparsely described. To compare growth in children with a history of AKI compared to those without AKI. We hypothesized that children with AKI would have worse growth compared to those without AKI. A convenience sample of existing prospective and retrospective cohorts of children with AKI who had already collected or were able to collect data on growth parameters before and after an episode of AKI. There are < 5 studies in the published literature on growth in children with AKI. These investigators were contacted, and additional studies were added by contacting primary investigators of studies of childhood AKI in which data on growth parameters was able to be collected. Children from existing cohorts evaluating AKI (exposure) during childhood. Each included cohort had previously received local IRB approval per institutional guidelines. As our study was a meta-analysis and only used cohort-level data, no IRB approval was required for this report. Growth parameters (length and weight z-scores) before and after an episode of AKI were compared using a meta-means analysis. MOOSE guidelines were used. Data were pooled using a random-effects model. Hedges g was calculated, and Higgins I2 statistic was used to define variability due to between-cohort heterogeneity. We included 3,586 children from 17 existing cohorts of AKI in various populations, including infants, children with cardiac disease, solid organ transplant and critically ill children without cardiac disease with follow-up from 12 months to 11 years after AKI. At most distant follow-up, those with AKI had lower length z-score than those without AKI (mean difference -0.37 [95

Sex differences exist in acute kidney injury (AKI), and the role that sex and gender play along the AKI care continuum remains unclear. The 33rd Acute Disease Quality Initiative meeting evaluated available data on the role of sex and gender in AKI and identified knowledge gaps. Data from experimental models, pathophysiology, epidemiology, clinical care, gender, social determinants of health, education, and advocacy were reviewed. Recommendations include incorporating sex and gender into research along the bench-to-bedside spectrum, analyzing sex-stratified results, evaluating the effects of sex chromosomes, hormones, and gender on outcomes, considering fluctuations of hormone levels, studying the impact gender may have on access to care, and developing educational tools to inform patients, providers, and stakeholders. This meeting report summarizes what is known about sex and gender along the AKI care continuum and proposes an agenda for translational discovery to elucidate the role of sex and gender in AKI across the lifespan.

In critical illness, all elements of gut function are perturbed. Dysbiosis develops as the gut microbial community loses taxonomic diversity and new virulence factors appear. Intestinal permeability increases, allowing for translocation of bacteria and/or bacterial products. Epithelial function is altered at a cellular level and homeostasis of the epithelial monolayer is compromised by increased intestinal epithelial cell death and decreased proliferation. Gut immunity is impaired with simultaneous activation of maladaptive pro- and anti-inflammatory signals leading to both tissue damage and susceptibility to infections. Additionally, splanchnic vasoconstriction leads to decreased blood flow with local ischemic changes. Together, these interrelated elements of gastrointestinal dysfunction drive and then perpetuate multi-organ dysfunction syndrome. Despite the clear importance of maintaining gut homeostasis, there are very few reliable measures of gut function in critical illness. Further, while multiple therapeutic strategies have been proposed, most have not been shown to conclusively demonstrate benefit, and care is still largely supportive. The key role of the gut in critical illness was the subject of the tenth Perioperative Quality Initiative meeting, a conference to summarize the current state of the literature and identify key knowledge gaps for future study. This review is the product of that conference.

How sex and gender are considered in randomized controlled trials (RCTs) in critical care nephrology is unclear. We aimed to perform a meta-epidemiologic study to describe the representation, sex and gender reporting, and sex- and gender-based analyses (SGBA) in high-impact RCTs in critical care nephrology. We searched the Web of Science Core Collection for critical care nephrology papers from 2000 to 2024. We included trials published in high-impact journals in general medicine, pediatrics, critical care, and nephrology. The main outcome was the proportion of female/woman participants enrolled and the association with trial characteristics, findings, and women authorship. We estimated the participation-to-prevalence ratio (PPR) to evaluate the representativeness of females within identified RCTs and selected case-mix and disease populations. Sex and gender reporting and SGBA were investigated. A total of 117 RCTs, including 106,057 participants, were included. Sex (54.7

There are limited studies evaluating hyperglycemia in children treated with continuous kidney replacement therapy (CKRT). We evaluated the association of hyperglycemia with kidney outcomes in critically ill children treated with CKRT for acute kidney injury (AKI) or fluid overload. Secondary analysis of the multicenter retrospective observational Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) study (34 centers, 9 countries). Primary exposure was hyperglycemia on days 0–7 of CKRT (average serum glucose of ≥ 150 mg/dL). Average serum glucose < 150 mg/dL was defined as euglycemic. We stratified the hyperglycemic group with cut-offs ≥ 180 mg/dL, ≥ 200 mg/dL, or ≥ 250 mg/dL. The primary outcome was MAKE-90 (death by 90 days or persistent kidney dysfunction [> 125

INTRODUCTION:Recent studies have identified an association between regional citrate anticoagulation (RCA) and subsequent infectious complications during continuous renal replacement therapy (CRRT). We aimed to determine if RCA was associated with infectious complications in children and young adults receiving CRRT. METHODS:A secondary analysis of the multinational Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK) registry (34 centers, 9 countries), was performed, including patients from 2015 to 2018. Patients were excluded if they (1) died within 72 h of CRRT initiation, had minor trauma or were postsurgical (analysis 1), or (2) met an exclusion in analysis 1 or had sepsis prior to CRRT initiation or chronic immunosuppression (analysis 2). Multivariable mixed-effects logistic (analysis 1) and mixed-effects Cox regression (analysis 2) were used to determine the associations between anticoagulant type and culture-positive infection after CRRT initiation. RESULTS:A total of 874 patients were included in analysis 1 and 283 in analysis 2. Culture-positive infection occurred in 25% and 17% of each analysis. In analysis 1, culture-positive infection was higher in RCA (29%) vs. heparin (23%) and other (15%); p = 0.008. There was no association between RCA and infection in multivariable analysis. In analysis 2, there was no difference in the frequency of infection by anticoagulation type. A longer time to achieve the first negative fluid balance was associated with culture-positive infection. CONCLUSION:RCA was not associated with culture-positive infection after CRRT initiation in this study. The systemic effects of AKI and longer time to first negative fluid balance may be inciting factors for an infection and represent a potentially modifiable factor that warrants future studies in this high-risk population.

INTRODUCTION:Neonatal acute kidney injury disproportionately affects extremely low birthweight (ELBW) infants (<1,000 g), who are especially vulnerable to fluid imbalance and its consequences. Current renal replacement therapy options are not optimized for patients under 2.5 kg. The Brophy Kit™, a cost-conscious, manual single-lumen dialysis device, may address this gap. METHODS:A preclinical feasibility study was conducted using eight healthy male Sprague Dawley rats (600-800 g), approximating the weight and blood volume of ELBW neonates. Each rat underwent 3-French catheter placement and sequential ultrafiltration (UF) cycles with the Brophy Kit™, targeting 5% and 10% blood volume removal. Respiratory rate was monitored as a surrogate for procedural tolerance. RESULTS:All eight animals tolerated the procedure and survived to UF completion. One rat was excluded due to catheter clotting before UF initiation. Respiratory rates remained stable throughout. Observed UF volumes deviated from prescribed volumes at the end of each experiment day by 11-12%. CONCLUSION:This proof-of-concept study demonstrates the feasibility of using the Brophy Kit™ for manual UF in a preclinical model approximating ELBW neonates. The device shows potential as an accessible solution for fluid management in resource-limited settings.

Adverse short- and long-term kidney outcomes are increasingly recognized as sequelae of NICU care, oftentimes of multifactorial origin and in the setting of a patent ductus arteriosus (PDA). Many studies have reviewed the interactions between the PDA and the brain, intestine, and lungs, but few have specifically reviewed the potential influence of the PDA on the kidney. This review describes the current breadth of literature as it relates to the pathophysiologic interplay between the PDA and the kidneys, as well as how PDA intervention may influence kidney health while neonates are still in the NICU and after discharge. We also discuss novel methods of monitoring these interactions with biomarkers and near infrared spectroscopy, and highlight areas with a dearth of evidence to promote future study.