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Browsing by Author "Barreto, Erin"
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Item Advances in pediatric acute kidney injury pathobiology: a report from the 26th Acute Disease Quality Initiative (ADQI) conference(Springer, 2024) Starr, Michelle C.; Barreto, Erin; Charlton, Jennifer; Vega, Molly; Brophy, Patrick D.; Bignall, O. N. Ray, II; Sutherland, Scott M.; Menon, Shina; Devarajan, Prasad; Arikan, Ayse Akcan; Basu, Rajit; Goldstein, Stuart; Soranno, Danielle E.; ADQI 26 workgroup; Pediatrics, School of MedicineBackground: 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.Item Advances in pediatric acute kidney injury pharmacology and nutrition: a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference(Springer, 2024) Wong Vega, Molly; Starr, Michelle C.; Brophy, Patrick D.; Devarajan, Prasad; Soranno, Danielle E.; Akcan‑Arikan, Ayse; Basu, Rajit; Goldstein, Stuart L.; Charlton, Jennifer R.; Barreto, Erin; Pediatrics, School of MedicineBackground: 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.Item Consensus-Based Recommendations on Priority Activities to Address Acute Kidney Injury in Children: A Modified Delphi Consensus Statement(American Medical Association, 2022-09-01) Goldstein, Stuart L.; Akcan-Arikan, Ayse; Alobaidi, Rashid; Askenazi, David J.; Bagshaw, Sean M.; Barhight, Matthew; Barreto, Erin; Bayrakci, Benan; Bignall, Orville N. R.; Bjornstad, Erica; Brophy, Patrick D.; Chanchlani, Rahul; Charlton, Jennifer R.; Conroy, Andrea L.; Deep, Akash; Devarajan, Prasad; Dolan, Kristin; Fuhrman, Dana Y.; Gist, Katja M.; Gorga, Stephen M.; Greenberg, Jason H.; Hasson, Denise; Heydari Ulrich, Emma; Iyengar, Arpana; Jetton, Jennifer G.; Krawczeski, Catherine; Meigs, Leslie; Menon, Shina; Morgan, Jolyn; Morgan, Catherine J.; Mottes, Theresa; Neumayr, Tara M.; Ricci, Zaccaria; Selewski, David; Soranno, Danielle E.; Starr, Michelle; Stanski, Natalja L.; Sutherland, Scott M.; Symons, Jordan; Tavares, Marcelo S.; Wong Vega, Molly; Zappitelli, Michael; Ronco, Claudio; Mehta, Ravindra L.; Kellum, John; Ostermann, Marlies; Basu, Rajit K.; Pediatric ADQI Collaborative; Pediatrics, School of MedicineImportance: Increasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge. Objective: To develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy. Evidence review: At the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations. Findings: The meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy. Conclusions and relevance: Existing evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.Item A Novel Fluorescent Clinical Method to Rapidly Quantify Plasma Volume(Karger Publishers, 2019) Molitoris, Bruce A.; George, Anthony G.; Murray, Patrick T.; Meier, Daniel; Reilly, Erinn S.; Barreto, Erin; Sandoval, Ruben M.; Rizk, Dana V.; Shaw, Andrew D.; Peacock, W. Frank; Medicine, School of MedicineObjectives To determine the performance of a rapid fluorescent indicator technique for measuring plasma volume (PV). Methods This was an open-label, observational evaluation of a two-component intravenous visible fluorescent dye technique to rapidly measure PV in 16 healthy subjects and 16 subjects with chronic kidney disease (8 stage 3 and 8 stage 4 CKD), at 2 clinical research sites. The method consisted of a single intravenous injection of 12 mg of a large 150-kDa carboxy-methyl dextran conjugated to a fluorescent rhodamine-derived dye as the PV marker (PVM), and 35 mg of a small 5-kDa carboxy-methyl dextran conjugated to fluorescein, the renal clearance marker. Dye concentrations were quantified 15 min after the injections for initial PV measurements using the indicator-dilution principle. Additional samples were taken over 8 h to evaluate the stability of the PVM as a determinant of PV. Blood volumes (BV) were calculated based on PV and the subject’s hematocrit. Pharmacokinetic parameters were calculated from the plasma concentration data taken over several days using noncompartmental methods (Phoenix WinNonlin®). Linear correlation and Bland-Altman plots were used to compare visible fluorescent injectate-measured PV compared to Nadler’s formula for estimating PV. Finally, 8 healthy subjects received 350 mL infusion of a 5% albumin solution in normal saline over 30 min and a repeat PV determination was then carried out. Results PV and BV varied according to weight and body surface area, with PV ranging from 2,115 to 6,234 mL and 28.6 to 41.9 mL/kg when weight adjusted. Both parameters were stable for > 6 h with repeated plasma measurements of the PVM. There was no difference between healthy subjects and CKD subjects. Overall, there was general agreement with Nadler’s estimation formula for the mean PV in subjects. A 24-h repeat dose measurement in 8 healthy subjects showed PV variability of 98 ± 121 mL (mean = 3.8%). Additionally, following an intravenous bolus of 350 mL of a 5% albumin solution in normal saline in 8 healthy subjects, the mean (SD) measured increase in PV was 356 (±50.0) mL post-infusion. There were no serious adverse events reported during the study. Conclusions This minimally invasive fluorescent dye approach safely allowed for rapid, accurate, and reproducible determination of PV, BV, and dynamic monitoring of changes following fluid administration.Item Pediatric AKI in the real world: changing outcomes through education and advocacy-a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference(Springer, 2024) Mottes, Theresa; Menon, Shina; Conroy, Andrea; Jetton, Jennifer; Dolan, Kristin; Arikan, Ayse Akcan; Basu, Rajit K.; Goldstein, Stuart L.; Symons, Jordan M.; Alobaid, Rashid; Askenazi, David J.; Bagshaw, Sean M.; Barhight, Matthew; Barreto, Erin; Bayrakci, Benan; Bignall, O. N., II; Bjornstad, Erica; Brophy, Patrick; Charlton, Jennifer; Chanchlani, Rahul; Conroy, Andrea L.; Deep, Akash; Devarajan, Prasad; Fuhrman, Dana; Gist, Katja M.; Gorga, Stephen M.; Greenberg, Jason H.; Hasson, Denise; Heydari, Emma; Iyengar, Arpana; Krawczeski, Catherine; Meigs, Leslie; Morgan, Catherine; Morgan, Jolyn; Neumayr, Tara; Ricci, Zaccaria; Selewski, David T.; Soranno, Danielle; Stanski, Natalja; Starr, Michelle; Sutherland, Scott M.; Symons, Jordan; Tavares, Marcelo; Vega, Molly; Zappitelli, Michael; Ronco, Claudio; Mehta, Ravindra L.; Kellum, John; Ostermann, Marlies; ADQI 26 workgroup; Pediatrics, School of MedicineBackground: 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.