Advocating for the inclusion of kidney health outcomes in neonatal research: best practice recommendations by the Neonatal Kidney Collaborative.

Acute kidney injury (AKI) occurs in nearly 30% of sick neonates. Chronic kidney disease (CKD) can be detected in certain populations of sick neonates as early as 2 years. AKI is often part of a multisystem syndrome that negatively impacts developing organs resulting in short- and long-term pulmonary, neurodevelopmental, and cardiovascular morbidities. It is critical to incorporate kidney-related data into neonatal clinical trials in a uniform manner to better understand how neonatal AKI or CKD could affect an outcome of interest. Here, we provide expert opinion recommendations and rationales to support the inclusion of short- and long-term neonatal kidney outcomes using a tiered approach based on study design: (1) observational studies (prospective or retrospective) limited to data available within a center's standard practice, (2) observational studies involving prospective data collection where prespecified kidney outcomes are included in the design, (3) interventional studies with non-nephrotoxic agents, and (4) interventional studies with known nephrotoxic agents. We also provide recommendations for biospecimen collection to facilitate ancillary kidney specific research initiatives. This approach balances the costs of AKI and CKD ascertainment with knowledge gained. We advocate that kidney outcomes be included routinely in neonatal clinical study design. Consistent incorporation of kidney outcomes across studies will increase our knowledge of neonatal morbidity.

Responding to the workforce crisis: consensus recommendations from the Second Workforce Summit of the American Society of Pediatric Nephrology.

IMPORTANCE: Pediatric patients with complex medical problems benefit from pediatric sub-specialty care; however, a significant proportion of children live greater than 80 mi. away from pediatric sub-specialty care. OBJECTIVE: To identify current knowledge gaps and outline concrete next steps to make progress on issues that have persistently challenged the pediatric nephrology workforce. EVIDENCE REVIEW: Workforce Summit 2.0 employed the round table format and methodology for consensus building using adapted Delphi principles. Content domains were identified via input from the ASPN Workforce Committee, the ASPN's 2023 Strategic Plan survey, the ASPN's Pediatric Nephrology Division Directors survey, and ongoing feedback from ASPN members. Working groups met prior to the Summit to conduct an organized literature review and establish key questions to be addressed. The Summit was held in-person in November 2023. During the Summit, work groups presented their preliminary findings, and the at-large group developed the key action statements and future directions. FINDINGS: A holistic appraisal of the effort required to cover inpatient and outpatient sub-specialty care will help define faculty effort and time distribution. Most pediatric nephrologists practice in academic settings, so work beyond clinical care including education, research, advocacy, and administrative/service tasks may form a substantial amount of a faculty member's time and effort. An academic relative value unit (RVU) may assist in creating a more inclusive assessment of their contributions to their academic practice. Pediatric sub-specialties, such as nephrology, contribute to the clinical mission and care of their institutions beyond their direct billable RVUs. Advocacy throughout the field of pediatrics is necessary in order for reimbursement of pediatric sub-specialist care to accurately reflect the time and effort required to address complex care needs. Flexible, individualized training pathways may improve recruitment into sub-specialty fields such as nephrology. CONCLUSIONS AND RELEVANCE: The workforce crisis facing the pediatric nephrology field is echoed throughout many pediatric sub-specialties. Efforts to improve recruitment, retention, and reimbursement are necessary to improve the care delivered to pediatric patients.

Over-the-Counter Hearing Aids Challenge the Core Values of Traditional Audiology.

PURPOSE: Regulatory changes in the United States introduced over-the-counter (OTC) hearing aids with the goal of increasing the accessibility and affordability of hearing health care. It is critical to understand the values inherent to hearing health care systems to evaluate their effectiveness in serving people with hearing difficulty. In this study, we evaluated the relative importance of values across service delivery models and the extent to which the introduction of OTC hearing aids represents a values shift relative to traditional audiology. METHOD: We performed a qualitative content analysis of two document categories: critique documents that motivated the creation of OTC hearing aids and regulatory documents that defined OTC hearing aids. Team members coded portions of text for the values they expressed. In total, 29,235 words were coded across 72 pages in four documents. Rank-order analyses were performed to determine the prioritization of values within each category of documents and subsequently compare values between OTC and traditional audiology documents analyzed in a previous study. RESULTS: Critique and regulatory documents both prioritized values related to reducing barriers to hearing aid access and use, but the lack of a significant correlation in the rank order of values in these documents was evidence of inconsistency between the motivation and implementation of OTC hearing aids. Differences in the rank order of values in the OTC documents compared to traditional audiology were consistent with a values shift. CONCLUSIONS: The introduction of OTC as a solution to low hearing aid use represents a values shift, challenging the values of traditional audiology. This research demonstrates a need to establish the values of hearing health care service delivery through a consensus of stakeholders, including individuals from diverse backgrounds underserved by the traditional model.

Continuous Kidney Replacement Therapy and Survival in Children and Young Adults: Findings From the Multinational WE-ROCK Collaborative.

RATIONALE & OBJECTIVE: There are limited studies describing the epidemiology and outcomes in children and young adults receiving continuous kidney replacement therapy (CKRT). We aimed to describe associations between patient characteristics, CKRT prescription, and survival. STUDY DESIGN: Retrospective multicenter cohort study. SETTING & PARTICIPANTS: 980 patients aged from birth to 25 years who received CKRT between 2015 and 2021 at 1 of 32 centers in 7 countries participating in WE-ROCK (Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Diseases). EXPOSURE: CKRT for acute kidney injury or volume overload. OUTCOMES: Death before intensive care unit (ICU) discharge. ANALYTICAL APPROACH: Descriptive statistics. RESULTS: Median age was 8.8 years (IQR, 1.6-15.0), and median weight was 26.8 (IQR, 11.6-55.0) kg. CKRT was initiated a median of 2 (IQR, 1-6) days after ICU admission and lasted a median of 6 (IQR, 3-14) days. The most common CKRT modality was continuous venovenous hemodiafiltration. Citrate anticoagulation was used in 62%, and the internal jugular vein was the most common catheter placement location (66%). 629 participants (64.1%) survived at least until ICU discharge. CKRT dose, filter type, and anticoagulation were similar in those who did and did not survive to ICU discharge. There were apparent practice variations by institutional ICU size. LIMITATIONS: Retrospective design; limited representation from centers outside the United States. CONCLUSIONS: In this study of children and young adults receiving CKRT, approximately two thirds survived at least until ICU discharge. Although variations in dialysis mode and dose, catheter size and location, and anticoagulation were observed, survival was not detected to be associated with these parameters. PLAIN-LANGUAGE SUMMARY: In this large contemporary epidemiological study of children and young adults receiving continuous kidney replacement therapy in the intensive care unit, we observed that two thirds of patients survived at least until ICU discharge. However, patients with comorbidities appeared to have worse outcomes. Compared with previously published reports on continuous kidney replacement therapy practice, we observed greater use of continuous venovenous hemodiafiltration with regional citrate anticoagulation.

Objectified kidney ultrasound echogenicity and size metrics as potential predictors for kidney function in children.

BACKGROUND: Kidney echogenicity is typically determined subjectively but may have a quantifiable relationship to kidney function. Similarly, kidney length has been shown to correlate with kidney function. This study sought to quantify echogenicity using readily available software. Secondarily, we aimed to evaluate the correlation between quantified echogenicity and kidney length to the estimated glomerular filtration rate (eGFR) in children with acute kidney injury (AKI) and chronic kidney disease (CKD). METHODS: In a single-center retrospective observational study, echogenicity index (EI) was determined using a ratio of right kidney to liver mean pixel density. The kidney length ratio (KLR) was determined by the actual to predicted lengths of both kidneys. Both variables were correlated to eGFR using correlation analyses and predictive capacity was determined with receiver operating characteristic curve (ROC) analysis. RESULTS: Of 94 subjects, 46% (43/94) had AKI, 28% (26/95) had CKD and 26% (25/95) were controls. The higher the EI the lower the eGFR (r = - 0.46, p < 0.0001). EI between 1.0 and 1.1 predicted an eGFR < 90 ml/min/1.73m2 with an AUC of 0.71-0.78 while an EI between 1.1 and 1.2 predicted an eGFR < 60 ml/min/1.73m2 with AUC of 0.75-0.80. Overall, the larger the KLR the lower the eGFR (r = - 0.25, p 0.018). CONCLUSION: We have developed an accessible methodology to quantify kidney echogenicity. Overall, there was an inverse correlation between EI and eGFR in pediatric CKD and AKI. However, these correlations did not persist within subgroups which could be due to small sample size and heterogeneity of etiologies. Overall, KLR had a weaker correlation to eGFR, compared to EI. Despite these correlations, both EI and KLR had "fair" to "good" performance as a biomarker for an eGFR < 60 ml/min/1.73m2.

Pediatric AKI in the real world: changing outcomes through education and advocacy-a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

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.

Advances in pediatric acute kidney injury pathobiology: a report from the 26th Acute Disease Quality Initiative (ADQI) conference.

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.

Using aquapheresis with continuous hematocrit monitoring to guide ultrafiltration.

BACKGROUND: Management of edema and volume overload in patients with hypoalbuminemia, either due to nephrotic syndrome or other disease processes, can be extremely challenging. METHODS: We describe the management of five patients with hypoalbuminemia and severe fluid overload using the Aquadex FlexFlow device with continuous hematocrit monitoring to guide ultrafiltration. RESULTS: We report five pediatric patients ranging in age from 7 days to 11 years and in size from 2.7 to 65 kg with hypoalbuminemia due to a variety of etiologies treated with slow continuous ultrafiltration with continuous hematocrit monitoring to guide ultrafiltration using the Aquadex device. Treatment allowed successful fluid removal in all cases, without hypotension or other hemodynamic complications. CONCLUSIONS: In a variety of clinical circumstances and in patients from infants to adolescence, we report that patients with diuretic-resistant fluid overload can be treated with Aquadex using continuous hematocrit monitoring to guide management to allow fluid removal without hemodynamic instability or other complications. A higher resolution version of the Graphical abstract is available as Supplementary information.

Advances in pediatric acute kidney injury pharmacology and nutrition: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

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.

Blood Pressure Outcomes in NICU-Admitted Infants with Neonatal Hypertension: A Pediatric Nephrology Research Consortium Study.

OBJECTIVE: To describe the blood pressure outcomes of infants admitted to the neonatal intensive care unit (NICU) with idiopathic (nonsecondary) hypertension (HTN) who were discharged on antihypertensive therapy. STUDY DESIGN: Retrospective, multicenter study of 14 centers within the Pediatric Nephrology Research Consortium. We included all infants with a diagnosis of idiopathic HTN discharged from the NICU on antihypertensive treatment. The primary outcome was time to discontinuation of antihypertensive therapy, grouped into (≤6 months, >6 months to 1 year, and >1 year). Comparisons between groups were made with χ2 tests, Fisher's exact tests, and ANOVA. RESULTS: Data from 118 infants (66% male) were included. Calcium channel blockers were the most prescribed class of antihypertensives (56%) in the cohort. The percentages remaining on antihypertensives after NICU discharge were 60% at 6 months, 26% at 1 year, and 7% at 2 years. Antenatal steroid treatment was associated with decreased likelihood of antihypertensive therapy >1 year after discharge. CONCLUSIONS: This multicenter study reports that most infants admitted to the NICU diagnosed with idiopathic HTN will discontinue antihypertensive treatment by 2 years after NICU discharge. These data provide important insights into the outcome of neonatal HTN, but should be confirmed prospectively.

Recent Advances in Kidney Replacement Therapy in Infants: A Review.

Kidney replacement therapy (KRT) is used to treat children and adults with acute kidney injury (AKI), fluid overload, kidney failure, inborn errors of metabolism, and severe electrolyte abnormalities. Peritoneal dialysis and extracorporeal hemodialysis/filtration can be performed for different durations (intermittent, prolonged intermittent, and continuous) through either adaptation of adult devices or use of infant-specific devices. Each of these modalities have advantages and disadvantages, and often multiple modalities are used depending on the scenario and patient-specific needs. Traditionally, these therapies have been challenging to deliver in infants due the lack of infant-specific devices, small patient size, required extracorporeal volumes, and the risk of hemodynamic stability during the initiation of KRT. In this review, we discuss challenges, recent advancements, and optimal approaches to provide KRT in hospitalized infants, including a discussion of peritoneal dialysis and extracorporeal therapies. We discuss each specific KRT modality, review newer infant-specific devices, and highlight the benefits and limitations of each modality. We also discuss the ethical implications for the care of infants who need KRT and areas for future research.

Adults are just big kids: pediatric considerations for adult critical care nephrology.

PURPOSE OF REVIEW: In recent years, there has been growing attention to pediatric kidney health, especially pediatric acute kidney injury (AKI). However, there has been limited focus on the role of pediatric AKI on adult kidney health, specifically considerations for the critical care physician. RECENT FINDINGS: We summarize what is known in the field of pediatric AKI to inform adult medical care including factors throughout the early life course, including perinatal, neonatal, and pediatric exposures that impact survivor care later in adulthood. SUMMARY: The number of pediatric AKI survivors continues to increase, leading to a higher burden of chronic kidney disease and other long-term co-morbidities later in life. Adult medical providers should consider pediatric history and illnesses to inform the care they provide. Such knowledge may help internists, nephrologists, and intensivists alike to improve risk stratification, including a lower threshold for monitoring for AKI and kidney dysfunction in their patients.

Acute Kidney Injury Defined by Fluid-Corrected Creatinine in Premature Neonates: A Secondary Analysis of the PENUT Randomized Clinical Trial.

Importance: Acute kidney injury (AKI) and disordered fluid balance are common in premature neonates; a positive fluid balance dilutes serum creatinine, and a negative fluid balance concentrates serum creatinine, both of which complicate AKI diagnosis. Correcting serum creatinine for fluid balance may improve diagnosis and increase diagnostic accuracy for AKI. Objective: To determine whether correcting serum creatinine for fluid balance would identify additional neonates with AKI and alter the association of AKI with short-term and long-term outcomes. Design, Setting, and Participants: This study was a post hoc cohort analysis of the Preterm Erythropoietin Neuroprotection Trial (PENUT), a phase 3, randomized clinical trial of erythropoietin, conducted at 19 academic centers and 30 neonatal intensive care units in the US from December 2013 to September 2016. Participants included extremely premature neonates born at less than 28 weeks of gestation. Data analysis was conducted in December 2022. Exposure: Diagnosis of fluid-corrected AKI during the first 14 postnatal days, calculated using fluid-corrected serum creatinine (defined as serum creatinine multiplied by fluid balance [calculated as percentage change from birth weight] divided by total body water [estimated 80% of birth weight]). Main Outcomes and Measures: The primary outcome was invasive mechanical ventilation on postnatal day 14. Secondary outcomes included death, hospital length of stay, and severe bronchopulmonary dysplasia (BPD). Categorical variables were analyzed by proportional differences with the χ2 test or Fisher exact test. The t test and Wilcoxon rank sums test were used to compare continuous and ordinal variables, respectively. Odds ratios (ORs) and 95% CIs for the association of exposure with outcomes of interest were estimated using unconditional logistic regression models. Results: A total of 923 premature neonates (479 boys [51.9%]; median [IQR] birth weight, 801 [668-940] g) were included, of whom 215 (23.3%) received a diagnosis of AKI using uncorrected serum creatinine. After fluid balance correction, 13 neonates with AKI were reclassified as not having fluid-corrected AKI, and 111 neonates previously without AKI were reclassified as having fluid-corrected AKI (ie, unveiled AKI). Therefore, fluid-corrected AKI was diagnosed in 313 neonates (33.9%). Neonates with unveiled AKI were similar in clinical characteristics to those with AKI whose diagnoses were made with uncorrected serum creatinine. Compared with those without AKI, neonates with unveiled AKI were more likely to require ventilation (81 neonates [75.0%] vs 254 neonates [44.3%] and have longer hospital stays (median [IQR], 102 [84-124] days vs 90 [71-110] days). In multivariable analysis, a diagnosis of fluid-corrected AKI was associated with increased odds of adverse clinical outcomes, including ventilation (adjusted OR, 2.23; 95% CI, 1.56-3.18) and severe BPD (adjusted OR, 2.05; 95% CI, 1.15-3.64). Conclusions and Relevance: In this post hoc cohort study of premature neonates, fluid correction increased the number of premature neonates with a diagnosis of AKI and was associated with increased odds of adverse clinical outcomes, including ventilation and BPD. Failing to correct serum creatinine for fluid balance underestimates the prevalence and impact of AKI in premature neonates. Future studies should consider correcting AKI for fluid balance. Trial Registration: ClinicalTrials.gov Identifier: NCT01378273.

Development of a Family-Centered Communication Tool for Kidney Health in Premature Infants: Qualitative Focus Group Study Using Human-Centered Design Methodology.

BACKGROUND: Premature infants are at increased risk of kidney-related complications, including acute kidney injury (AKI) and chronic kidney disease (CKD). The risk of CKD in prematurely born infants is underrecognized by health care teams and caregivers. Understanding how to communicate the risk of CKD to caregivers is essential for longitudinal clinical follow-up and adherence. OBJECTIVE: This study aimed to determine family caregiver attitudes toward kidney health and risk communication during a neonatal intensive care admission. We also sought to understand caregiver preferences for the communication of information surrounding the risk of CKD in premature infants. METHODS: We augmented standard qualitative group sessions with human-centered design methods to assess parent preferences and clinician perspectives. Caregivers recruited had a prematurely born child who spent time in the neonatal intensive care unit at Riley Hospital for Children in Indianapolis, Indiana, and experienced AKI or another kidney complication, which put them at risk for future CKD. We used a variety of specific design methods in these sessions, including card sorting, projective methods, experience mapping, and constructive methods. RESULTS: A total of 7 clinicians and 8 caregivers participated in 3 group sessions. Caregivers and clinicians readily acknowledged barriers to and drivers of long-term kidney monitoring as well as opportunities for communication of the risk of long-term kidney disease. Caregivers' primary concerns were for both the type and depth of information conveyed as well as the time at which it was communicated. Participants emphasized the importance of collaboration between the hospital care team and the primary care provider. Participant input was synthesized into several prototype concepts and, ultimately, into a rough prototype of a website and an informational flyer. CONCLUSIONS: Caregivers of premature infants are open to communication about kidney health during their neonatal admission. The next phase of this work will translate caregivers' preferences into family-centered communication tools and test their efficacy in the neonatal intensive care unit.

Core Values in the Traditional Provision of Hearing Health Care.

PURPOSE: Untreated hearing loss is a significant public health issue affecting the quality of life of millions of Americans. Barriers to treatment invite novel and innovation solutions, but as these solutions create new treatment delivery models, they also may-purposefully or accidentally-challenge the values of the field. METHOD: Value-sensitive design methodology is used in this study to identify the values in current hearing health care service delivery. We performed qualitative content analysis of questionnaires, clinical practice guidelines, and professional ethics documents that represent the intended and enacted values in audiology. RESULTS: The result is a comprehensive list of values that can be used as a structured codebook for systematic textual analysis of materials representing current best practices in the provision of hearing health care services. A secondary result is an analysis of the relative importance of values in audiology, inferred from the frequency of references to each value. CONCLUSIONS: Subjective benefit, professional duties, and self-efficacy were the core values identified in the current provision of audiologic care, and these values should be central to considerations for new hearing health care models and technologies.