Pediatric nephrology is dedicated to caring for children with kidney disease, a unique blend of acute care and chronic longitudinal patient relationships. Though historically a small field, trainee interest has declined over the past 2 decades. This has led to growing alarm about the health of the pediatric nephrology workforce, although concerns have been hampered by a lack of available data to enable feasible projections. This article is part of a supplement that anticipates the future pediatric subspecialty workforce supply. It draws on existing literature, data from the American Board of Pediatrics, and findings from a model that estimates the future supply of pediatric subspecialists developed by the Carolina Health Workforce Research Center at the University of North Carolina Chapel Hill's Cecil G. Sheps Center for Health Services Research and Strategic Modeling Analytics & Planning Ltd. The workforce projections from 2020 to 2040 incorporate population growth, clinical effort, and geographic trends and model alternate scenarios adjusting for changes in trainee interest, clinical efforts, and workforce attrition. The baseline model predicts growth of clinical work equivalents by 26% by 2040, but further widening geographic disparities worsen the existing mismatch between supply, clinical need, and market demand. The worst-case scenario projects 13% growth by 2040 which, at best, maintains the status quo of an already strained workforce. The models do not account for many factors expected to heighten demand over the coming decades. Urgent reforms are necessary now. Proposed solutions require multipronged changes in education and training pathways, remuneration, clinical practice models, and government policy.

Rationale & Objective: Children born before 28 weeks' gestation are at increased risk of chronic kidney disease (CKD). Urine biomarkers may shed light on mechanistic pathways and improve the ability to forecast CKD. We evaluated whether urinary biomarkers in neonates of low gestational age (GA) are associated with a reduced estimated glomerular fi ltration rate (eGFR) over time. Study Design: A cohort study of neonates with an exploratory case -control study of a subset of the cohort. Setting & Participants: 327 neonates born at 24-27 weeks' gestation with 2 -year eGFR data from the PENUT (Preterm Erythropoietin Neuroprotection Trial) and the REPaIReD (Recombinant Erythropoietin for Prevention of Infant Renal Disease) study. Exposures: 11 urinary biomarkers measured at 27, 30, and 34 weeks' postmenstrual age for the primary cohort study and 10 additional biomarkers for the exploratory case -control study. Outcomes: eGFR < 90 mL/min/1.73 m(2) at 2 years corrected for GA. Analytical Approach: Linear mixed models to assess differences in biomarker values between neonates in whom CKD did and did not develop, accounting for multiple comparisons using Bonferroni-Holm correction in the cohort study only. Cohort analyses were adjusted for sex, GA, and body mass index. Cases were matched to controls on these variables in the casecontrol study. Results: After adjusting for weeks of GA, urinary levels of alpha- glut athione-S-transferase (log difference, 0.27; 95% CI, 0.12-0.43), albumin (log difference, 0.13; 95% CI, 0.02-0.25), and cysatin C (log difference, 0.19; 95% CI, 0.04-0.3 4) were higher in those in whom CKD developed than in those in whom it did not. Urinary albumin and cystatin C levels did not remain signi fi cantly different after Bonferroni-Holm correction. In the exploratory case -control analysis, there were no differences in any biomarkers between cases and controls. Limitations: Early deaths and a high number of subjects without eGFR at 2 years corrected for GA. Conclusions: Measurement of urinary biomarkers may assist in monitoring neonates who are at risk for CKD. Additional studies are needed to con fi rm these fi ndings. Funding: Grants from government (National Institutes of Health).

Children represent the leading edge of demographic changes and the growing diversity of the US. According to the US Census, as of 2021, "minority" (Non-Hispanic Black, Non-Hispanic Asian, Native American, and Hispanic) children now constitute 44.9% of the childhood population less than 18 years of age. By 2050, it is projected that this will grow to over 50%.1

There is a recognized need to promote greater diversity in the pediatric workforce and pediatric academic leadership, aiming to achieve greater numbers of pediatricians who are under-represented in medicine (URM).1 A department chair can play a prominent role in prioritizing URM recruitment as well as retention. In addition, if the chairs themselves self-identify as URM, they can also serve as visible leaders and role models for current and future URM trainees and faculty.2 Other leadership roles, such as vice chair, division chief, fellowship director, or clinic director may have a similar effect. To understand the current diversity in leadership positions in academic pediatrics, we conducted a survey of medical school-affiliated academic pediatrics department chairs and other pediatrics departmental leadership positions in the US and Canada. Division chiefs, program directors, and vice chairs are often leading candidates for open department chair positions.3 As a result, the current diversity of these other leadership roles within departments of pediatrics may provide a window into the trajectory of future diversity of pediatrics chairs and workforce.

BACKGROUND:In the past decade, there have been substantial advances in our understanding of pediatric AKI. Despite this progress, large gaps remain in our understanding of pharmacology and nutritional therapy in pediatric AKI. METHODS:During the 26th Acute Disease Quality Initiative (ADQI) Consensus Conference, a multidisciplinary group of experts reviewed the evidence and used a modified Delphi process to achieve consensus on recommendations for gaps and advances in care for pharmacologic and nutritional management of pediatric AKI. The current evidence as well as gaps and opportunities were discussed, and recommendations were summarized. RESULTS:Two consensus statements were developed. (1) High-value, kidney-eliminated medications should be selected for a detailed characterization of their pharmacokinetics, pharmacodynamics, and pharmaco-"omics" in sick children across the developmental continuum. This will allow for the optimization of real-time modeling with the goal of improving patient care. Nephrotoxin stewardship will be identified as an organizational priority and supported with necessary resources and infrastructure. (2) Patient-centered outcomes (functional status, quality of life, and optimal growth and development) must drive targeted nutritional interventions to optimize short- and long-term nutrition. Measures of acute and chronic changes of anthropometrics, body composition, physical function, and metabolic control should be incorporated into nutritional assessments. CONCLUSIONS:Neonates and children have unique metabolic and growth parameters compared to adult patients. Strategic investments in multidisciplinary translational research efforts are required to fill the knowledge gaps in nutritional requirements and pharmacological best practices for children with or at risk for AKI.

BACKGROUND:Acute kidney injury (AKI) is independently associated with increased morbidity and mortality across the life course, yet care for AKI remains mostly supportive. Raising awareness of this life-threatening clinical syndrome through education and advocacy efforts is the key to improving patient outcomes. Here, we describe the unique roles education and advocacy play in the care of children with AKI, discuss the importance of customizing educational outreach efforts to individual groups and contexts, and highlight the opportunities created through innovations and partnerships to optimize lifelong health outcomes. METHODS:During the 26th Acute Disease Quality Initiative (ADQI) consensus conference, a multidisciplinary group of experts discussed the evidence and used a modified Delphi process to achieve consensus on recommendations on AKI research, education, practice, and advocacy in children. RESULTS:The consensus statements developed in response to three critical questions about the role of education and advocacy in pediatric AKI care are presented here along with a summary of available evidence and recommendations for both clinical care and research. CONCLUSIONS:These consensus statements emphasize that high-quality care for patients with AKI begins in the community with education and awareness campaigns to identify those at risk for AKI. Education is the key across all healthcare and non-healthcare settings to enhance early diagnosis and develop mitigation strategies, thereby improving outcomes for children with AKI. Strong advocacy efforts are essential for implementing these programs and building critical collaborations across all stakeholders and settings.

In this issue of Pediatrics, Meena et al demonstrate not only the notable incidence of acute kidney injury (AKI) among hospitalized pediatric patients worldwide but also the concerning discrepancy in AKI-related mortality as a function of a country’s income.1 With improvement in provider education and the implementation of tools to identify AKI early, incidence and associated mortality can be reduced. Through sustained efforts and policy implementation on the local, national, and global scale, we can work to eliminate mortality discrepancies.As described in the authors’ meta-analysis, one-quarter of hospitalized pediatric patients worldwide are diagnosed with AKI. The adoption of the 2012 Kidney Disease Improving Global Outcomes AKI definition has helped to standardize the diagnostic criteria.2 However, the use of serum creatinine and urine output-based classification system detects AKI once it is already established, leaving little window for preventive strategies.3 Thus, there is a need for tools to allow for earlier detection of AKI, as well as identification of those patients at the highest risk. Substantial progress has been made in the use of novel biomarkers that would allow providers to detect AKI before any overt clinical manifestation.2,3 The clinical application of these biomarkers and the widespread availability of their assays continue to be elucidated.For example, the Renal Angina Index has been used in pediatric patients on admission to the ICU to predict those at risk for the development of severe AKI.2,3 Prediction models have been used to develop electronic medical record alerts, which notify providers of patients at increased risk for AKI.3 Although these tools are beneficial, the intervention that is likely to have the greatest impact on AKI incidence is increased provider awareness and education.The majority of AKI is present on hospital admission, indicating that the injury commonly originates in the community setting. Kidney injury is often seen as an unavoidable consequence of acute illness. However, several interventions can be implemented to attenuate the development or worsening of kidney injury, including ensuring adequate intravascular fluid volume, minimizing exposure to nephrotoxic agents, and maintaining normotension. Development and provision of AKI mitigation guidance to all providers regardless of specialty is crucial, with a focus on patient risk assessment, timely AKI diagnosis, appropriate referral and intervention, and close monitoring that continues after the resolution of an AKI episode.4AKI is associated with increased morbidity and mortality in all pediatric patients, but, as demonstrated in this study, mortality risk is increased disproportionately in patients residing in low- and low-middle-income countries. The etiologies of kidney injury differ between lower-income and higher-income countries, and low-income countries also face specific difficulties related to a lack of resources. Despite the widespread use of the Kidney Disease Improving Global Outcomes AKI classification, many low- and middle-income countries lack comprehensive data registries describing the prevalence of kidney disease, making it more difficult to determine epidemiologic trends and identify areas in need of additional support.5,6 Low- and middle-income countries have a greater prevalence of certain microbes, poor sanitation, and lack of supply of safe drinking water, all of which contribute to increased risk of infection, dehydration, and subsequent development of AKI.5With respect to AKI treatment, there is often inadequate infrastructure and reduced means available for travel to a major medical center to receive appropriate care. Even within the major medical centers in low- and middle-income countries, access to the standard of care treatment is often limited because of inadequate resources. Continuous kidney replacement therapy is the treatment of choice for severe AKI; however, it is costly and requires significant training and support staff. Many developing countries report preferential use of peritoneal dialysis because of ease of use, staffing support, and cost constraints.7Increased education and guidance surrounding preventive measures can help decrease the overall incidence of pediatric AKI worldwide, and early detection and prompt intervention will help mitigate associated morbidity and mortality. Clinical and policy-based strategies to ensure provider training, improved infrastructure, and increased funding are needed to improve equity in AKI outcomes.

Hypoxic ischemic encephalopathy (HIE) occurs in 2-5/1000 births, with acute kidney injury (AKI) occurring in 40%. AKI increases morbidity and mortality. Caffeine, an adenosine receptor antagonist, and photobiomodulation (PBM), working on cytochrome c oxidase, are potential treatments for AKI. To examine effects of caffeine and PBM on AKI in rats, Day 7 pups underwent a HIE intervention (Modified Rice-Vannucci model) replicating pathology observed in humans. Caffeine was administered for 3 days and/or PBM for 5 days following HIE. Weights and urine for biomarkers (NGAL, albumin, KIM-1, osteopontin) were collected prior to HIE, daily post intervention and at sacrifice. Both treatments reduced kidney injury seen on electron microscopy, but not when combined. HIE elevated urinary NGAL and albumin on Days 1-3 post-HIE, before returning to control levels. This elevation was significantly reduced by PBM or caffeine. KIM-1 was significantly elevated for 7 days post-HIE and was reduced by both treatments. Osteopontin was not altered by HIE or the treatments. Treatments, individually but not in combination, improved HIE-induced reductions in the enzymatic activity of mitochondrial complexes II-III. PBM and caffeine also improved weight gain. PBM and caffeine reduces AKI diagnosed by urinary biomarkers and confirmed by EM findings.

Continuous renal replacement therapy (CRRT) in pediatrics follows similar principles utilized in caring for adult patients. There are, however, some key factors that add complexity to the care and implementation of CRRT in the smallest of patients. This chapter provides an overview of the principles and practice of CRRT in the neonatal and pediatric populations.

Acute kidney injury (AKI) following cardiopulmonary bypass (CPB) is associated with increased morbidity and mortality. Serum Cystatin C (CysC) is a novel biomarker synthesized by all nucleated cells that may act as an early indicator of AKI following infant CPB. Prospective observational study of infants (< 1 year) requiring CPB during cardiac surgery. CysC was measured at baseline and 12, 24, 48, and 72 h following CPB initiation. Each post-op percent difference in CysC (e.g.

BACKGROUND:In the past decade, there have been substantial advances in our understanding of the pathobiology of pediatric acute kidney injury (AKI). In particular, animal models and studies focused on the relationship between kidney development, nephron number, and kidney health have identified a number of heterogeneous pathophysiologies underlying AKI. Despite this progress, gaps remain in our understanding of the pathobiology of pediatric AKI. METHODS:During the 26th Acute Disease Quality Initiative (ADQI) Consensus conference, a multidisciplinary group of experts discussed the evidence and used a modified Delphi process to achieve consensus on recommendations for opportunities to advance translational research in pediatric AKI. The current state of research understanding as well as gaps and opportunities for advancement in research was discussed, and recommendations were summarized. RESULTS:Consensus was reached that to improve translational pediatric AKI advancements, diverse teams spanning pre-clinical to epidemiological scientists must work in concert together and that results must be shared with the community we serve with patient involvement. Public and private research support and meaningful partnerships with adult research efforts are required. Particular focus is warranted to investigate the pediatric nuances of AKI, including the effect of development as a biological variable on AKI incidence, severity, and outcomes. CONCLUSIONS:Although AKI is common and associated with significant morbidity, the biologic basis of the disease spectrum throughout varying nephron developmental stages remains poorly understood. An incomplete understanding of factors contributing to kidney health, the diverse pathobiologies underlying AKI in children, and the historically siloed approach to research limit advances in the field. The recommendations outlined herein identify gaps and outline a strategic approach to advance the field of pediatric AKI via multidisciplinary translational research.

Introduction:Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI.Methods:We analyzed data from the Drug-Induced Renal Injury Consortium (DIRECT) study (NCT02159209), an international, multicenter, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least 1 nephrotoxic drug for a minimum of 24 hours prior to AKI onset. Cases were clinically adjudicated, and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC).Results:A total of 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), nonsteroidal antiinflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine (SCr) trends, and contrast media as significant predictors of DI-AKI with good performance (ROC AUC 0.86).Conclusion:The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies.

Despite a growing understanding of bronchopulmonary dysplasia (BPD) and advances in management, BPD rates remain stable. There is mounting evidence that BPD may be due to a systemic insult, such as acute kidney injury (AKI). Our hypothesis was that severe AKI would be associated with BPD. We conducted a secondary analysis of premature infants [24–27 weeks gestation] in the Recombinant Erythropoietin for Protection of Infant Renal Disease cohort (N = 885). We evaluated the composite outcome of Grade 2/3 BPD or death using generalized estimating equations. In an exploratory analysis, urinary biomarkers of angiogenesis (ANG1, ANG2, EPO, PIGF, TIE2, FGF, and VEGFA/D) were analyzed. 594 (67.1%) of infants had the primary composite outcome of Grade 2/3 BPD or death. Infants with AKI (aOR: 1.69, 95% CI: 1.16–2.46) and severe AKI (aOR: 2.05, 95% CI: 1.19–3.54). had increased risk of the composite outcome after multivariable adjustment Among 106 infants with urinary biomarkers assessed, three biomarkers (VEGFA, VEGFD, and TIE2) had AUC > 0.60 to predict BPD. Infants with AKI had a higher likelihood of developing BPD/death, with the strongest relationship seen in those with more severe AKI. Three urinary biomarkers of angiogenesis may have potential to predict BPD development.

Objective To investigate the associations between neurocognition and white matter integrity in children with chronic kidney disease (CKD). Study design This cross-sectional study included 17 boys (age 6-16 years) with a diagnosis of mild to moderate (stages 1-3, nondialysis/nontransplant) CKD because of congenital anomalies of the kidney and urinary tract and 20 typically developing community controls. Participants underwent 3T neuroimaging and diffusion-weighted magnetic resonance imaging to assess white matter fractional anisotropy. Multivariable linear regression models were used to evaluate the impact of each group (controls vs CKD) on white matter fractional anisotropy, adjusting for age. Associations between white matter fractional anisotropy and neurocognitive abilities within the CKD group were also evaluated using regression models that were adjusted for age. The false discovery rate was used to account for multiple comparisons; wherein false discovery values <0.10 were considered significant. Results Global white matter fractional anisotropy was reduced in patients with CKD relative to controls (standardized estimate = -0.38, 95% CI -0.69:-0.07), driven by reductions within the body of the corpus callosum (standardized estimate = -0.44, 95% CI -0.75:-0.13), cerebral peduncle (SE = -0.37, 95% CI -0.67:-0.07), cingulum (hippocampus) (standardized estimate = -0.45, 95% CI -0.75:-0.14), and posterior limb of the internal capsule (standardized estimate = -0.46, 95% CI -0.76:-0.15). Medical variables and neurocognitive abilities were not significantly associated with white matter fractional anisotropy. Conclusions White matter development is vulnerable in children with CKD because of congenital causes, even prior to the need for dialysis or transplantation.

Hematopoietic cell transplantation (HCT) is a common therapy for the treatment of neoplastic and metabolic disorders, hematological diseases, and fatal immunological deficiencies. HCT can be subcategorized as autologous or allogeneic, with each modality being associated with their own benefits, risks, and post-transplant complications. One of the most common complications includes acute kidney injury (AKI). However, diagnosing HCT patients with AKI early on remains quite difficult. Therefore, this evidence-based guideline, compiled by the Pediatric Continuous Renal Replacement Therapy (PCRRT) working group, presents the various factors that contribute to AKI and recommendations regarding optimization of therapy with minimal complications in HCT patients.

Hypoxic ischemic encephalopathy (HIE) is associated with acute kidney injury (AKI) in neonates with birth asphyxia. This study aimed to utilize urinary biomarkers to characterize AKI in an established neonatal rat model of HIE. Day 7 Sprague-Dawley rat pups underwent HIE using the Rice-Vannucci model (unilateral carotid ligation followed by 120 mins of 8% oxygen). Controls included no surgery and sham surgery. Weights and urine for biomarkers (NGAL, osteopontin, KIM-1, albumin) were collected the day prior, daily for 3days post-intervention, and at sacrifice day 14. Kidneys and brains were processed for histology. HIE pups displayed histological evidence of kidney injury including damage to the proximal tubules, consistent with resolving acute tubular necrosis, and had significantly elevated urinary levels of NGAL and albumin compared to sham or controls 1-day post-insult that elevated for 3days. KIM-1 significantly increased for 2days post-HIE. HIE did not significantly alter osteopon tin levels. Seven days post-start of experiment, controls were 81.2% above starting weight compared to 52.1% in HIE pups. NGAL and albumin levels inversely correlated with body weight following HIE injury. The AKI produced by the Rice-Vannucci HIE model is detectable by urinary biomarkers, which can be used for future studies of treatments to reduce kidney injury.