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A growing body of research is categorizing sex differences in both sickle cell anemia (SCA) and acute kidney injury (AKI); however, most of this work is being conducted in high-resource settings. Here, we evaluated risk factors and clinical parameters associated with AKI and AKI severity, stratified by sex, in a cohort of children hospitalized with SCA and vaso-occlusive pain crisis (VOC). The purpose of this study was to explore sex disparities in a high-risk, vulnerable population. This study was a secondary analysis of data collected from a cohort of Ugandan children between 2 and 18 yr of age prospectively enrolled. A total of 185 children were enrolled in the primary study; 41.6% were female and 58.4% were male, with a median age of 8.9 yr. Incident or worsening AKI (P = 0.026) occurred more frequently in female compared with male children, despite no differences in AKI on admission. Female children also had altered markers of renal function including higher creatinine levels at admission (P = 0.03), higher peak creatinine (P = 0.006), and higher urine neutrophil gelatinase-associated lipocalin (NGAL) at admission (P = 0.003) compared with male children. Female children had elevated total (P = 0.045) and conjugated bilirubin at admission (P = 0.02) compared with male children and higher rates of hematuria at admission (P = 0.004). Here, we report sex differences in AKI in children with SCA and VOC, including increased incidence and worsening of AKI in female pediatric patients, in association with an increase in biological indicators of poor renal function including creatinine, estimated glomerular filtration rate, and NGAL.NEW & NOTEWORTHY In this study, we report an increased risk of developing acute kidney injury (AKI) during hospitalization, worsening AKI, and death among females with sickle cell anemia (SCA) hospitalized with an acute pain crisis compared with males. The sex differences in AKI were not explained by socioeconomic differences, severity of pain, or disease severity among females compared with males. Together, these data suggest that female children with SCA may be at increased risk of AKI.
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Injúria Renal Aguda , Anemia Falciforme , Humanos , Anemia Falciforme/complicações , Anemia Falciforme/epidemiologia , Feminino , Masculino , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/urina , Injúria Renal Aguda/diagnóstico , Criança , Uganda/epidemiologia , Pré-Escolar , Adolescente , Fatores Sexuais , Fatores de Risco , Incidência , Biomarcadores/sangue , Biomarcadores/urina , Hospitalização , Estudos Prospectivos , Índice de Gravidade de Doença , Lipocalina-2/urina , Rim/fisiopatologiaRESUMO
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.
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Injúria Renal Aguda , Adulto , Animais , Humanos , Criança , Doença Aguda , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Incidência , Consenso , Modelos AnimaisRESUMO
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.
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Injúria Renal Aguda , Qualidade de Vida , Recém-Nascido , Adulto , Criança , Humanos , Doença Aguda , Injúria Renal Aguda/terapiaRESUMO
BACKGROUND: Access to pediatric dialysis is challenged in low-resource settings due to high costs, scarcity of equipment, and the lack of qualified personnel availability. We demonstrated the manual single lumen alternating micro-batch (mSLAMB) device can remove small solutes in vitro without the need for electricity, batteries, or pumps. We developed a new version (Kirpa Kit™) to address some of the technical limitations of mSLAMB. Here, we compare the in vitro clearance performance and ease of use of the Kirpa Kit™ with that of prior mSLAMB configurations. METHODS: A mixture of expired packed red blood cells, 0.9% NaCl, urea, and heparin was used to test the efficiency of two mSLAMB configurations and the Kirpa Kit™ in removing potassium and urea. Clearance was evaluated by measuring percent reduction after 25-min sessions with each device. A survey was used to evaluate the ease of use of each configuration. RESULTS: The Kirpa Kit™ achieved a median urea reduction of 82.4% and potassium reduction of 82.1%, which were higher than those achieved with the best-performing mSLAMB configuration (urea 71.9%, potassium 75.4%). The Kirpa Kit™ was easier to use with a shorter perceived time of use than the mSLAMB. CONCLUSIONS: The Kirpa Kit™, evolution of mSLAMB, is easy to use and may have improved efficacy, making it an optimal candidate for in vivo testing.
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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.
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OBJECTIVES: With the recognition that fluid overload (FO) has a detrimental impact on critically ill children, the critical care nephrology community has focused on identifying clinically meaningful targets for intervention. The current study aims to evaluate the epidemiology and outcomes associated with FO in an international multicenter cohort of critically ill children. The current study also aims to evaluate the association of FO at predetermined clinically relevant thresholds and time points (FO ≥ 5% and FO ≥ 10% at the end of ICU days 1 and 2) with outcomes. DESIGN: Prospective cohort study. SETTING: Multicenter, international collaborative of 32 pediatric ICUs. PATIENTS: A total of 5,079 children and young adults admitted consecutively to pediatric ICUs as part of the Assessment of the Worldwide Acute Kidney Injury, Renal Angina and Epidemiology Study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The FO thresholds at the time points of interest occurred commonly in the cohort (FO ≥ 5%Day1 in 38.1% [ n = 1753], FO ≥ 10%Day1 in 11.7% [ n = 537], FO ≥ 5%Day2 in 53.3% [ n = 1,539], FO ≥ 10%Day2 in 25.1% [ n = 724]). On Day1, multivariable modeling demonstrated that FO ≥ 5% was associated with fewer ICU-free days, and FO ≥ 10% was associated with higher mortality and fewer ICU and ventilator-free days. On multivariable modeling, FO-peak, Day2 FO ≥ 5%, and Day2 FO ≥ 10% were associated with higher mortality and fewer ICU and ventilator-free days. CONCLUSIONS: This study found that mild-to-moderate FO as early as at the end of ICU Day1 is associated with adverse outcomes. The current study fills an important void in the literature by identifying critical combinations of FO timing and quantity associated with adverse outcomes (FO ≥ 5%Day1, FO ≥10%Day1, FO ≥ 5%Day2, and FO ≥ 10%Day2). Those novel findings will help guide the development of interventional strategies and trials targeting the treatment and prevention of clinically relevant FO.
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Injúria Renal Aguda , Insuficiência Cardíaca , Desequilíbrio Hidroeletrolítico , Adulto Jovem , Humanos , Criança , Estado Terminal/epidemiologia , Estado Terminal/terapia , Estudos Prospectivos , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/terapia , Unidades de Terapia Intensiva PediátricaRESUMO
BACKGROUND: Acute kidney injury (AKI) is common in sick neonates and associated with poor pulmonary outcomes, however, the mechanisms responsible remain unknown. We present two novel neonatal rodent models of AKI to investigate the pulmonary effects of AKI. METHODS: In rat pups, AKI was induced surgically via bilateral ischemia-reperfusion injury (bIRI) or pharmacologically using aristolochic acid (AA). AKI was confirmed with plasma blood urea nitrogen and creatinine measurements and kidney injury molecule-1 staining on renal immunohistochemistry. Lung morphometrics were quantified with radial alveolar count and mean linear intercept, and angiogenesis investigated by pulmonary vessel density (PVD) and vascular endothelial growth factor (VEGF) protein expression. For the surgical model, bIRI, sham, and non-surgical pups were compared. For the pharmacologic model, AA pups were compared to vehicle controls. RESULTS: AKI occurred in bIRI and AA pups, and they demonstrated decreased alveolarization, PVD, and VEGF protein expression compared controls. Sham pups did not experience AKI, however, demonstrated decreased alveolarization, PVD, and VEGF protein expression compared to controls. CONCLUSION: Pharmacologic AKI and surgery in neonatal rat pups, with or without AKI, decreased alveolarization and angiogenesis, producing a bronchopulmonary dysplasia phenotype. These models provide a framework for elucidating the relationship between AKI and adverse pulmonary outcomes. IMPACT: There are no published neonatal rodent models investigating the pulmonary effects after neonatal acute kidney injury, despite known clinical associations. We present two novel neonatal rodent models of acute kidney injury to study the impact of acute kidney injury on the developing lung. We demonstrate the pulmonary effects of both ischemia-reperfusion injury and nephrotoxin-induced AKI on the developing lung, with decreased alveolarization and angiogenesis, mimicking the lung phenotype of bronchopulmonary dysplasia. Neonatal rodent models of acute kidney injury provide opportunities to study mechanisms of kidney-lung crosstalk and novel therapeutics in the context of acute kidney injury in a premature infant.
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Injúria Renal Aguda , Displasia Broncopulmonar , Traumatismo por Reperfusão , Humanos , Recém-Nascido , Animais , Ratos , Animais Recém-Nascidos , Displasia Broncopulmonar/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Pulmão , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/metabolismoRESUMO
PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the preclinical and clinical studies investigating sex as a biological variable, as well as the impact of gender, on the development of and progression of acute kidney injury (AKI). RECENT FINDINGS: Despite a matched degree of ischemia-reperfusion AKI based on measured glomerular filtration rates, male and female mice demonstrated important sex biases in cardiorenal outcomes (1). Although the 2012 Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guideline for AKI reported that female sex is associated with increased rates of hospital acquired AKI, subsequent meta-analyses do not show increased risk of AKI in women. Recent large scale, multicenter epidemiologic studies suggest males have higher rates of hospital acquired AKI. However, women have been consistently shown to have worse renal outcomes after AKI. There may be also be gender-based differences in presentation to care and management. SUMMARY: Sex is an important biological variable in animal models of acute kidney injury. The impact of sex on AKI likely varies based on the etiology of AKI. Preclinical studies demonstrate the nuances of sex chromosomes, sex hormones and epigenetic factors on AKI, however these have not been well studied in humans. Gender may also impact processes of care, treatment and clinical outcomes related to AKI. The scientific rigor and reproducibility of translational studies benefit from the consideration of sex and gender.
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Injúria Renal Aguda , Humanos , Masculino , Feminino , Animais , Camundongos , Reprodutibilidade dos Testes , Fatores de Risco , Injúria Renal Aguda/terapia , Rim , Taxa de Filtração Glomerular , Estudos Retrospectivos , Estudos Multicêntricos como AssuntoRESUMO
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.
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Injúria Renal Aguda , Nefrologia , Insuficiência Renal Crônica , Recém-Nascido , Humanos , Criança , Adulto , Rim , Injúria Renal Aguda/terapia , Cuidados CríticosRESUMO
In order to develop a standardized nomenclature for the mechanisms and materials utilized during extracorporeal blood purification, a consensus expert conference was convened in November 2022. Standardized nomenclature serves as a common language for reporting research findings, new device development, and education. It is also critically important to support patient safety, allow comparisons between techniques, materials, and devices, and be essential for defining and naming innovative technologies and classifying devices for regulatory approval. The multidisciplinary conference developed detailed descriptions of the performance characteristics of devices (membranes, filters, and sorbents), solute and fluid transport mechanisms, flow parameters, and methods of treatment evaluation. In addition, nomenclature for adsorptive blood purification techniques was proposed. This report summarizes these activities and highlights the need for standardization of nomenclature in the future to harmonize research, education, and innovation in extracorporeal blood purification therapies.
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15-Lipoxygenase (15-LO) is a nonheme iron-containing dioxygenase that has both pro- and anti-inflammatory roles in many tissues and disease states. 15-LO is thought to influence macrophage phenotype, and silencing 15-LO reduces fibrosis after acute inflammatory triggers. The goal of the present study was to determine whether altering 15-LO expression influences inflammation and fibrogenesis in a murine model of unilateral ureteral obstruction (UUO). C57BL/6J mice, 15-LO knockout (Alox15-/-) mice, and 15-LO transgenic overexpressing (15LOTG) mice were subjected UUO, and kidneys were analyzed at 3, 10, and 14 days postinjury. Histology for fibrosis, inflammation, cytokine quantification, flow cytometry, and metabolomics were performed on injured tissues and controls. PD146176, a specific 15-LO inhibitor, was used to complement experiments involving knockout animals. Compared with wild-type animals undergoing UUO, Alox15-/- mouse kidneys had less proinflammatory, profibrotic message along with less fibrosis and macrophage infiltration. PD146176 inhibited 15-LO and resulted in reduced fibrosis and macrophage infiltration similar to Alox15-/- mice. Flow cytometry revealed that Alox15-/- UUO-injured kidneys had a dynamic change in macrophage phenotype, with an early blunting of CD11bHiLy6CHi "M1" macrophages and an increase in anti-inflammatory CD11bHiLy6CInt "M2c" macrophages and reduced expression of the fractalkine receptor chemokine (C-X3-C motif) receptor 1. Many of these findings were reversed when UUO was performed on 15LOTG mice. Metabolomics analysis revealed that wild-type kidneys developed a glycolytic shift postinjury, while Alox15-/- kidneys exhibited increased oxidative phosphorylation. In conclusion, 15-LO manipulation by genetic or pharmacological means induces dynamic changes in the inflammatory microenvironment in the UUO model and appears to be critical in the progression of UUO-induced fibrosis.NEW & NOTEWORTHY 15-Lipoxygenase (15-LO) has both pro- and anti-inflammatory functions in leukocytes, and its role in kidney injury and repair is unexplored. Our study showed that 15-LO worsens inflammation and fibrosis in a rodent model of chronic kidney disease using genetic and pharmacological manipulation. Silencing 15-LO promotes an increase in M2c-like wound-healing macrophages in the kidney and alters kidney metabolism globally, protecting against anaerobic glycolysis after injury.
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Araquidonato 12-Lipoxigenase/metabolismo , Araquidonato 15-Lipoxigenase/metabolismo , Citocinas/metabolismo , Metabolismo Energético , Mediadores da Inflamação/metabolismo , Rim/enzimologia , Metaboloma , Nefrite/etiologia , Obstrução Ureteral/complicações , Animais , Araquidonato 12-Lipoxigenase/genética , Araquidonato 15-Lipoxigenase/genética , Microambiente Celular , Citocinas/genética , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Fibrose , Rim/efeitos dos fármacos , Rim/patologia , Leucócitos/enzimologia , Inibidores de Lipoxigenase/farmacologia , Macrófagos/enzimologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nefrite/enzimologia , Nefrite/patologia , Nefrite/prevenção & controle , Fenótipo , Obstrução Ureteral/tratamento farmacológico , Obstrução Ureteral/enzimologia , Obstrução Ureteral/patologiaRESUMO
Acute kidney injury (AKI) is a common cause of morbidity after congenital heart disease surgery. Progress on diagnosis and therapy remains limited, however, in part due to poor mechanistic understanding and a lack of relevant translational models. Metabolomic approaches could help identify novel mechanisms of injury and potential therapeutic targets. In the present study, we used a piglet model of cardiopulmonary bypass with deep hypothermic circulatory arrest (CPB/DHCA) and targeted metabolic profiling of kidney tissue, urine, and serum to evaluate metabolic changes specific to animals with histological acute kidney injury. CPB/DHCA animals with acute kidney injury were compared with those without acute kidney injury and mechanically ventilated controls. Acute kidney injury occurred in 10 of 20 CPB/DHCA animals 4 h after CPB/DHCA and 0 of 7 control animals. Injured kidneys showed a distinct tissue metabolic profile compared with uninjured kidneys (R2 = 0.93, Q2 = 0.53), with evidence of dysregulated tryptophan and purine metabolism. Nine urine metabolites differed significantly in animals with acute kidney injury with a pattern suggestive of increased aerobic glycolysis. Dysregulated metabolites in kidney tissue and urine did not overlap. CPB/DHCA strongly affected the serum metabolic profile, with only one metabolite that differed significantly with acute kidney injury (pyroglutamic acid, a marker of oxidative stress). In conclusion, based on these findings, kidney tryptophan and purine metabolism are candidates for further mechanistic and therapeutic investigation. Urine biomarkers of aerobic glycolysis could help diagnose early acute kidney injury after CPB/DHCA and warrant further evaluation. The serum metabolites measured at this early time point did not strongly differentiate based on acute kidney injury.NEW & NOTEWORTHY This project explored the metabolic underpinnings of postoperative acute kidney injury (AKI) following pediatric cardiac surgery in a translationally relevant large animal model of cardiopulmonary bypass with deep hypothermic circulatory arrest. Here, we present novel evidence for dysregulated tryptophan catabolism and purine catabolism in kidney tissue and increased urinary glycolysis intermediates in animals who developed histological AKI. These pathways represent potential diagnostic and therapeutic targets for postoperative AKI in this high-risk population.
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Injúria Renal Aguda , Procedimentos Cirúrgicos Cardíacos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Animais , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ponte Cardiopulmonar/efeitos adversos , Parada Circulatória Induzida por Hipotermia Profunda/efeitos adversos , Humanos , Rim , Purinas , Suínos , TriptofanoRESUMO
PURPOSE OF REVIEW: The purpose of this review is to describe acute kidney injury (AKI) phenotypes in children. RECENT FINDINGS: AKI is a heterogenous disease that imposes significant morbidity and mortality on critically ill and noncritically ill patients across the age spectrum. As our understanding of AKI and its association with outcomes has improved, it is becoming increasingly apparent that there are distinct AKI subphenotypes that vary by cause or associated conditions. We have also learned that severity, duration, and repeated episodes of AKI impact outcomes, and that integration of novel urinary biomarkers of tubular injury can also reveal unique subphenotypes of AKI that may not be otherwise readily apparent. SUMMARY: Studies that further delineate these unique AKI subphenotypes are needed to better understand the impact of AKI in children. Further delineation of these phenotypes has both prognostic and therapeutic implications.
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Injúria Renal Aguda , Humanos , Injúria Renal Aguda/diagnóstico , Estado Terminal , Biomarcadores , FenótipoRESUMO
OBJECTIVES: Quality improvement initiatives to decrease rates of nephrotoxic medication exposure have reduced rates of acute kidney injury (AKI) in noncritically ill children. The objective of our study was to analyze the implementation of a similar program in critically ill children and to measure important balancing measures including opioid and benzodiazepine exposure. DESIGN: Prospective quality improvement study. SETTING: PICU at Children's Hospital Colorado between 2018 and 2020. PATIENTS: All children admitted to PICU. INTERVENTIONS: Quality improvement initiative called Nephrotoxic Injury Negated by Just-In-Time Action (NINJA). MEASUREMENT AND MAIN RESULTS: Eight thousand eight hundred thirty-three PICU patient admissions were included. Mean rates of nephrotoxic medication exposure/1,000 PICU patient days decreased from 46 to 26, whereas rates of nephrotoxic AKI/1,000 PICU patient days did not change. Nonsteroidal anti-inflammatory drug dispenses per 1,000 patient days were reduced from 521 to 456. Similarly, opioid and benzodiazepine exposures per 1,000 patient days were reduced from 812 to 524 and 441 to 227, respectively, during the study observation period. CONCLUSIONS: The NINJA intervention was efficaciously implemented in our single-center PICU. Nephrotoxic exposure is a modifiable factor that did not inadvertently increase exposure to opioids and benzodiazepines.
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Injúria Renal Aguda , Analgésicos Opioides , Criança , Humanos , Lactente , Estudos Prospectivos , Analgésicos Opioides/efeitos adversos , Estado Terminal/terapia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Benzodiazepinas/efeitos adversos , DorRESUMO
BACKGROUND: Adult studies have demonstrated potential harm from resuscitation with 0.9% sodium chloride (0.9%NaCl), resulting in increased utilization of balanced crystalloids like lactated ringers (LR). The sodium and potassium content of LR has resulted in theoretical safety concerns, although limited data exists in pediatrics. We hypothesized that use of LR for resuscitation would not be associated with increased electrolyte derangements compared to 0.9%NaCl. METHODS: A prospective, observational cohort study of critically ill children who received ≥ 20 ml/kg of fluid resuscitation and were admitted to two pediatric intensive care units from November 2017 to February 2020. Fluid groups included patients who received > 75% of fluids from 0.9%NaCl, > 75% of fluids from LR, and a mixed group. The primary outcome was incidence of electrolyte derangements (sodium, chloride, potassium) and acidosis. RESULTS: Among 559 patients, 297 (53%) received predominantly 0.9%NaCl, 74 (13%) received predominantly LR, and 188 (34%) received a mixture. Extreme hyperkalemia (potassium ≥ 6 mmol/L) was more common in 0.9%NaCl group (5.8%) compared to LR group (0%), p 0.05. Extreme acidosis (pH > 7.1) was more common in 0.9%NaCl group (11%) compared to LR group (1.6%), p 0.016. CONCLUSIONS: LR is associated with fewer electrolyte derangements compared to 0.9%NaCl. Prospective interventional trials are needed to validate these findings.
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Projetos de Pesquisa , Sódio , Humanos , Criança , Soluções Cristaloides/uso terapêutico , Estudos Prospectivos , PotássioRESUMO
BACKGROUND: Acute kidney injury is a common complication following the Norwood operation. Most neonatal studies report acute kidney injury peaking within the first 48 hours after cardiac surgery. The aim of this study was to evaluate if persistent acute kidney injury (>48 postoperative hours) after the Norwood operation was associated with clinically relevant outcomes. METHODS: Two-centre retrospective study among neonates undergoing the Norwood operation. Acute kidney injury was initially identified as developing within the first 48 hours after cardiac surgery and stratified into transient (≤48 hours) and persistent (>48 hours) using the neonatal modification of the Kidney Disease: Improving Global Outcomes serum creatinine criteria. Severe was defined as stage ≥2. Primary and secondary outcomes were mortality and duration of ventilation and hospital length of stay. RESULTS: One hundred sixty-eight patients were included. Transient and persistent acute kidney injuries occurred in 24 and 17%, respectively. Cardiopulmonary bypass and aortic cross clamp duration, and incidence of cardiac arrest were greater among those with persistent kidney injury. Mortality was four times higher (41 versus 12%, p < 0.001) and mechanical ventilation duration 50 hours longer in persistent acute kidney injury patients (158 versus 107 hours; p < 0.001). In multivariable analysis, persistent acute kidney injury was not associated with mortality, duration of ventilation or length of stay. Severe persistent acute kidney injury was associated with a 59% increase in expected ventilation duration (aIRR:1.59, 95% CI:1.16, 2.18; p = 0.004). CONCLUSIONS: Future large studies are needed to determine if risk factors and outcomes change by delineating acute kidney injury into discrete timing phenotypes.
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Injúria Renal Aguda , Procedimentos de Norwood , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Feminino , Humanos , Masculino , Procedimentos de Norwood/efeitos adversos , Fenótipo , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVES: Acute kidney injury is diagnosed according to creatinine and urine output criteria. Traditionally, both are applied, and a severity stage (1-3) is conferred based upon the more severe of the two; information from the other criteria is discarded. Physiologically, however, rising creatinine and oliguria represent two distinct types of renal dysfunction. We hypothesized that using the information from both criteria would more accurately characterize acute kidney injury severity and outcomes. DESIGN: Prospective cohort study. SETTING: Multicenter, international collaborative of ICUs. PATIENTS: Three thousand four hundred twenty-nine children and young adults admitted consecutively to ICUs as part of the Assessment of the Worldwide Acute Kidney Injury, Renal Angina and Epidemiology Study. MEASUREMENTS AND MAIN RESULTS: The Kidney Disease: Improving Global Outcomes creatinine and urine output acute kidney injury criteria were applied sequentially, and the two stages were summed, generating an Acute Kidney Injury (AKI) Score ranging from 1 to 6. The primary outcome was 28-day mortality; secondary outcomes were time until ICU discharge and nonrecovery from acute kidney injury. Models considered associations with AKI Score, assessing the relationship unadjusted and adjusted for covariates. Twenty-eight-day mortality and nonrecovery from acute kidney injury were modeled using logistic regression. For 28-day ICU discharge, competing risks analysis was performed. Although AKI Scores 1-3 had similar mortality to no Acute Kidney Injury, AKI Scores 4-6 were associated with increased mortality. Relative to No Acute Kidney Injury, AKI Scores 1-6 were less likely to be discharged from the ICU within 28 days. Relative to AKI Score 1, AKI Scores 2-6 were associated with higher risk of nonrecovery. Within the traditional Kidney Disease: Improving Global Outcomes Stage 3 acute kidney injury cohort, when compared with AKI Score 3, AKI Scores 4-6 had increased mortality, AKI Scores 5-6 had prolonged time to ICU discharge, and AKI Score 6 experienced higher nonrecovery rates. CONCLUSIONS: Cumulative application of the creatinine and urine output criteria characterizes renal excretory and fluid homeostatic dysfunction simultaneously. This Acute Kidney Injury score more comprehensively describes the outcome implications of severe acute kidney injury than traditional staging methods.
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Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Creatinina/sangue , Estado Terminal/epidemiologia , Índice de Gravidade de Doença , Micção/fisiologia , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/urina , Adolescente , Criança , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
Neutrophil gelatinase associated lipocalin (NGAL, Lcn2) is the most widely studied biomarker of acute kidney injury (AKI). Previous studies have demonstrated that NGAL is produced by the kidney and released into the urine and plasma. Consequently, NGAL is currently considered a tubule specific injury marker of AKI. However, the utility of NGAL to predict AKI has been variable suggesting that other mechanisms of production are present. IL-6 is a proinflammatory cytokine increased in plasma by two hours of AKI and mediates distant organ effects. Herein, we investigated the role of IL-6 in renal and extra-renal NGAL production. Wild type mice with ischemic AKI had increased plasma IL-6, increased hepatic NGAL mRNA, increased plasma NGAL, and increased urine NGAL; all reduced in IL-6 knockout mice. Intravenous IL-6 in normal mice increased hepatic NGAL mRNA, plasma NGAL and urine NGAL. In mice with hepatocyte specific NGAL deletion (Lcn2hep-/-) and ischemic AKI, hepatic NGAL mRNA was absent, and plasma and urine NGAL were reduced. Since urine NGAL levels appear to be dependent on plasma levels, the renal handling of circulating NGAL was examined using recombinant human NGAL. After intravenous recombinant human NGAL administration to mice, human NGAL in mouse urine was detected by ELISA during proximal tubular dysfunction, but not in pre-renal azotemia. Thus, during AKI, IL-6 mediates hepatic NGAL production, hepatocytes are the primary source of plasma and urine NGAL, and plasma NGAL appears in the urine during proximal tubule dysfunction. Hence, our data change the paradigm by which NGAL should be interpreted as a biomarker of AKI.
Assuntos
Injúria Renal Aguda , Lipocalinas , Injúria Renal Aguda/diagnóstico , Proteínas de Fase Aguda/genética , Animais , Biomarcadores , Hepatócitos , Interleucina-6 , Lipocalina-2/genética , CamundongosRESUMO
BACKGROUND: Serum chloride derangements are associated with poor clinical outcomes, including acute kidney injury (AKI) and mortality. We sought to determine the association between persistent hyperchloremia and renal recovery in critically ill children with AKI. METHODS: We performed a retrospective cohort study of all patients with day 2 AKI admitted to a large academic pediatric intensive care unit from January 2014 to December 2015. After applying exclusion criteria, 348 patients were categorized as (1) hyperchloremia on both day 2 and day 7 (PersistentCl), (2) hyperchloremia on day 2 with normochloremia on day 7 (RecoveredCl), (3) normochloremia on day 2 with hyperchloremia on day 7 (DelayedCl), and (4) no hyperchloremia on day 2 nor day 7 (NormalCl). Hyperchloremia was defined as ≥ 110 mEq/L. The primary outcome was renal recovery on day 7, defined as the absence of AKI criteria. Secondary outcomes included discharge renal recovery, mortality, duration of mechanical ventilation, and hospital length of stay. RESULTS: Day 7 renal recovery rates for PersistentCl, RecoveredCl, DelayedCl, and NormalCl were 37%, 66%, 71%, and 52% respectively. PersistentCl had lower odds of day 7 renal recovery (aOR = 0.29; 95% CI, 0.14 to 0.60; p = 0.0009), lower odds of discharge renal recovery (aOR = 0.22; 95% CI, 0.11 to 0.48; p = 0.0001), and higher odds of mortality (aOR = 3.50; 95% CI, 1.11 to 11.10; p = 0.03) when compared with RecoveredCl after adjusting for confounders. CONCLUSIONS: Persistent hyperchloremia is independently associated with impaired renal recovery as well as higher mortality. Prospective studies are indicated to determine if serum chloride represents a modifiable risk factor for poor outcomes. Graphical abstract.
Assuntos
Injúria Renal Aguda/mortalidade , Cloretos/sangue , Desequilíbrio Hidroeletrolítico/mortalidade , Injúria Renal Aguda/etiologia , Adolescente , Bicarbonatos/sangue , Criança , Pré-Escolar , Feminino , Humanos , Unidades de Terapia Intensiva Pediátrica , Masculino , Estudos Retrospectivos , Desequilíbrio Hidroeletrolítico/sangueRESUMO
OBJECTIVE: Acute kidney injury (AKI) is a common occurrence among hospitalized children and leads to increased mortality and prolonged length of stay (LOS) in critically ill patients. Few studies have examined the impact of AKI on LOS for common pediatric conditions. We hypothesized that a diagnosis of AKI would be associated with a longer hospital LOS and increased exposure to nephrotoxic medications for all patients. PATIENTS AND METHODS: We performed a multicenter retrospective cross-sectional analysis of 34 children's hospitals in the Pediatric Health Information System (PHIS) database from 1/2009 through 12/2013. Patients were grouped based on primary discharge diagnosis, number of days spent in an intensive care unit, and assignment of a secondary diagnostic code for AKI. Median LOS was compared among different patient groupings. Exposure to commonly used nephrotoxic medications was collected for each admission. RESULTS: A total of 588,884 admissions from 423,337 patients were included in the analysis. The median LOS among non-critically ill patients with and without AKI was 5 days [95% CI 3-10] versus 2 days [95% CI 1-4], respectively. Among critically ill patients, median LOS for those with and without AKI was 12 days [95% CI 7-20] versus 4 days [95% CI 2-7], respectively. Patients who developed AKI were more likely to have significant nephrotoxic exposure. CONCLUSIONS: Development of AKI was associated with longer hospital length of stay and increased nephrotoxic medication exposure for all diagnostic categories. Non-critically ill children with AKI were hospitalized the same length or longer than critically ill children without AKI.