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Browsing by Author "Akcan-Arikan, Ayse"
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Item Cerebrospinal fluid biomarkers provide evidence for kidney-brain axis involvement in cerebral malaria pathogenesis(Frontiers Media, 2023-05-02) Conroy, Andrea L.; Datta, Dibyadyuti; Opoka, Robert O.; Batte, Anthony; Bangirana, Paul; Gopinadhan, Adnan; Mellencamp, Kagan A.; Akcan-Arikan, Ayse; Idro, Richard; John, Chandy C.; Pediatrics, School of MedicineIntroduction: Cerebral malaria is one of the most severe manifestations of malaria and is a leading cause of acquired neurodisability in African children. Recent studies suggest acute kidney injury (AKI) is a risk factor for brain injury in cerebral malaria. The present study evaluates potential mechanisms of brain injury in cerebral malaria by evaluating changes in cerebrospinal fluid measures of brain injury with respect to severe malaria complications. Specifically, we attempt to delineate mechanisms of injury focusing on blood-brain-barrier integrity and acute metabolic changes that may underlie kidney-brain crosstalk in severe malaria. Methods: We evaluated 30 cerebrospinal fluid (CSF) markers of inflammation, oxidative stress, and brain injury in 168 Ugandan children aged 18 months to 12 years hospitalized with cerebral malaria. Eligible children were infected with Plasmodium falciparum and had unexplained coma. Acute kidney injury (AKI) on admission was defined using the Kidney Disease: Improving Global Outcomes criteria. We further evaluated blood-brain-barrier integrity and malaria retinopathy, and electrolyte and metabolic complications in serum. Results: The mean age of children was 3.8 years (SD, 1.9) and 40.5% were female. The prevalence of AKI was 46.3% and multi-organ dysfunction was common with 76.2% of children having at least one organ system affected in addition to coma. AKI and elevated blood urea nitrogen, but not other measures of disease severity (severe coma, seizures, jaundice, acidosis), were associated with increases in CSF markers of impaired blood-brain-barrier function, neuronal injury (neuron-specific enolase, tau), excitatory neurotransmission (kynurenine), as well as altered nitric oxide bioavailability and oxidative stress (p < 0.05 after adjustment for multiple testing). Further evaluation of potential mechanisms suggested that AKI may mediate or be associated with CSF changes through blood-brain-barrier disruption (p = 0.0014), ischemic injury seen by indirect ophthalmoscopy (p < 0.05), altered osmolality (p = 0.0006) and through alterations in the amino acids transported into the brain. Conclusion: In children with cerebral malaria, there is evidence of kidney-brain injury with multiple potential pathways identified. These changes were specific to the kidney and not observed in the context of other clinical complications.Item The Neglected Price of Pediatric Acute Kidney Injury: Non-renal Implications(Frontiers Media, 2022-06-30) Pande, Chetna K.; Smith, Mallory B.; Soranno, Danielle E.; Gist, Katja M.; Fuhrman, Dana Y.; Dolan, Kristin; Conroy, Andrea L.; Akcan-Arikan, Ayse; Pediatrics, School of MedicinePreclinical models and emerging translational data suggest that acute kidney injury (AKI) has far reaching effects on all other major organ systems in the body. Common in critically ill children and adults, AKI is independently associated with worse short and long term morbidity, as well as mortality, in these vulnerable populations. Evidence exists in adult populations regarding the impact AKI has on life course. Recently, non-renal organ effects of AKI have been highlighted in pediatric AKI survivors. Given the unique pediatric considerations related to somatic growth and neurodevelopmental consequences, pediatric AKI has the potential to fundamentally alter life course outcomes. In this article, we highlight the challenging and complex interplay between AKI and the brain, heart, lungs, immune system, growth, functional status, and longitudinal outcomes. Specifically, we discuss the biologic basis for how AKI may contribute to neurologic injury and neurodevelopment, cardiac dysfunction, acute lung injury, immunoparalysis and increased risk of infections, diminished somatic growth, worsened functional status and health related quality of life, and finally the impact on young adult health and life course outcomes.Item Pediatric Organ Dysfunction Information Update Mandate (PODIUM) Contemporary Organ Dysfunction Criteria: Executive Summary(American Academy of Pediatrics, 2022) Bembea, Melania M.; Agus, Michael; Akcan-Arikan, Ayse; Alexander, Peta; Basu, Rajit; Bennett, Tellen D.; Bohn, Desmond; Brandão, Leonardo R.; Brown, Ann-Marie; Carcillo, Joseph A.; Checchia, Paul; Cholette, Jill; Cheifetz, Ira M.; Cornell, Timothy; Doctor, Allan; Eckerle, Michelle; Erickson, Simon; Farris, Reid W.D.; Faustino, E. Vincent S.; Fitzgerald, Julie C.; Fuhrman, Dana Y.; Giuliano, John S.; Guilliams, Kristin; Gaies, Michael; Gorga, Stephen M.; Hall, Mark; Hanson, Sheila J.; Hartman, Mary; Hassinger, Amanda B.; Irving, Sharon Y.; Jeffries, Howard; Jouvet, Philippe; Kannan, Sujatha; Karam, Oliver; Khemani, Robinder G.; Kissoon, Niranjan; Lacroix, Jacques; Laussen, Peter; Leclerc, Francis; Lee, Jan Hau; Leteurtre, Stephane; Lobner, Katie; McKiernan, Patrick J.; Menon, Kusum; Monagle, Paul; Muszynski, Jennifer A.; Odetola, Folafoluwa; Parker, Robert; Pathan, Nazima; Pierce, Richard W.; Pineda, Jose; Prince, Jose M.; Robinson, Karen A.; Rowan, Courtney M.; Ryerson, Lindsay M.; Sanchez-Pinto, L. Nelson; Schlapbach, Luregn J.; Selewski, David T.; Shekerdemian, Lara S.; Simon, Dennis; Smith, Lincoln S.; Squires, James E.; Squires, Robert H.; Sutherland, Scott M.; Ouellette, Yves; Spaeder, Michael C.; Srinivasan, Vijay; Steiner, Marie E.; Tasker, Robert C.; Thiagarajan, Ravi; Thomas, Neal; Tissieres, Pierre; Traube, Chani; Tucci, Marisa; Typpo, Katri V.; Wainwright, Mark S.; Ward, Shan L.; Watson, R. Scott; Weiss, Scott; Whitney, Jane; Willson, Doug; Wynn, James L.; Yehya, Nadir; Zimmerman, Jerry J.; Pediatrics, School of MedicinePrior criteria for organ dysfunction in critically ill children were based mainly on expert opinion. We convened the Pediatric Organ Dysfunction Information Update Mandate (PODIUM) expert panel to summarize data characterizing single and multiple organ dysfunction and to derive contemporary criteria for pediatric organ dysfunction. The panel was composed of 88 members representing 47 institutions and 7 countries. We conducted systematic reviews of the literature to derive evidence-based criteria for single organ dysfunction for neurologic, cardiovascular, respiratory, gastrointestinal, acute liver, renal, hematologic, coagulation, endocrine, endothelial, and immune system dysfunction. We searched PubMed and Embase from January 1992 to January 2020. Study identification was accomplished using a combination of medical subject headings terms and keywords related to concepts of pediatric organ dysfunction. Electronic searches were performed by medical librarians. Studies were eligible for inclusion if the authors reported original data collected in critically ill children; evaluated performance characteristics of scoring tools or clinical assessments for organ dysfunction; and assessed a patient-centered, clinically meaningful outcome. Data were abstracted from each included study into an electronic data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. Consensus was achieved for a final set of 43 criteria for pediatric organ dysfunction through iterative voting and discussion. Although the PODIUM criteria for organ dysfunction were limited by available evidence and will require validation, they provide a contemporary foundation for researchers to identify and study single and multiple organ dysfunction in critically ill children.Item The Neglected Price of Pediatric Acute Kidney Injury: Non-renal Implications(Frontiers Media, 2022-06-30) Pande, Chetna K.; Smith, Mallory B.; Soranno, Danielle E.; Gist, Katja M.; Fuhrman, Dana Y.; Dolan, Kristin; Conroy, Andrea L.; Akcan-Arikan, Ayse; Pediatrics, School of MedicinePreclinical models and emerging translational data suggest that acute kidney injury (AKI) has far reaching effects on all other major organ systems in the body. Common in critically ill children and adults, AKI is independently associated with worse short and long term morbidity, as well as mortality, in these vulnerable populations. Evidence exists in adult populations regarding the impact AKI has on life course. Recently, non-renal organ effects of AKI have been highlighted in pediatric AKI survivors. Given the unique pediatric considerations related to somatic growth and neurodevelopmental consequences, pediatric AKI has the potential to fundamentally alter life course outcomes. In this article, we highlight the challenging and complex interplay between AKI and the brain, heart, lungs, immune system, growth, functional status, and longitudinal outcomes. Specifically, we discuss the biologic basis for how AKI may contribute to neurologic injury and neurodevelopment, cardiac dysfunction, acute lung injury, immunoparalysis and increased risk of infections, diminished somatic growth, worsened functional status and health related quality of life, and finally the impact on young adult health and life course outcomes.