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Glomerular filtration rate (GFR) is considered the best overall index of kidney function in health and disease and its use is recommended to evaluate the risk of iodine contrast medium-induced acute kidney injury (CI-AKI) either as a single parameter or as a ratio between the total contrast medium dose (gram iodine) and GFR. GFR may be expressed in absolute terms (mL/min) or adjusted/indexed to body surface area, relative GFR (mL/min/1.73 m2). Absolute and relative GFR have been used interchangeably to evaluate the risk of CI-AKI, which may be confusing and a potential source of errors. Relative GFR should be used to assess the GFR category of renal function as a sign of the degree of kidney damage and sensitivity for CI-AKI. Absolute GFR represents the excretion capacity of the individual and may be used to calculate the gram-iodine/absolute GFR ratio, an index of systemic drug exposure (amount of contrast medium in the body) that relates to toxicity. It has been found to be an independent predictor of AKI following percutaneous coronary angiography and interventions but has not yet been fully validated for computed tomography (CT). Prospective studies are warranted to evaluate the optimal gram-iodine/absolute GFR ratio to predict AKI at various stages of renal function at CT. Only GFR estimation (eGFR) equations based on standardized creatinine and/or cystatin C assays should be used. eGFRcystatin C/eGFRcreatinine ratio < 0.6 indicating selective glomerular hypofiltration syndrome may have a stronger predictive power for postcontrast AKI than creatinine-based eGFR. CLINICAL RELEVANCE STATEMENT: Once the degree of kidney damage is established by estimating relative GFR (mL/min/1.73 m2), contrast dose in relation to renal excretion capacity [gram-iodine/absolute GFR (mL/min)] may be the best index to evaluate the risk of contrast-induced kidney injury. KEY POINTS: • Relative glomerular filtration rate (GFR; mL/min/1.73 m2) should be used to assess the GFR categor, Correction in: Eur Radiol 34, 2123–2124 (2024).DOI: 10.1007/s00330-023-10199-w

OBJECTIVES: To determine if current clinical use of iodine contrast media (ICM) for computerised tomography (CT) increases the risk of acute kidney injury (AKI) and long-term decline in renal function in patients treated in intensive care. METHODS: A retrospective bi-centre cohort study was performed with critically ill subjects undergoing either ICM-enhanced or unenhanced CT. AKI was defined and staged based on the Kidney Disease Improve Global Outcome AKI criteria, using both creatinine and urine output criteria. Follow-up plasma creatinine was recorded three to six months after CT to assess any long-term effects of ICM on renal function. RESULTS: In total, 611 patients were included in the final analysis, median age was 65.0 years (48.0-73.0, quartile 1-quartile 3 (IQR)) and 62.5% were male. Renal replacement therapy was used post-CT in 12.9% and 180-day mortality was 31.2%. Plasma creatinine level on day of CT was 100.0 µmol/L (66.0-166.5, IQR) for non-ICM group and 77.0 µmol/L (59.0-109.0, IQR) for the ICM group. The adjusted odds ratio for developing AKI if the patient received ICM was 1.03 (95% confidence interval 0.64-1.66, p = 0.90). No significant association between ICM and increase in plasma creatinine at long-term follow-up was found, with an adjusted effect size of 2.92 (95% confidence interval - 6.52-12.36, p = 0.543). CONCLUSIONS: The results of this study do not indicate an increased risk of AKI or long-term decline in renal function when ICM is used for enhanced CT in patients treated at intensive care units. CLINICAL RELEVANCE STATEMENT: Patients treated in intensive care units had no increased risk of acute kidney injury or persistent decline in renal function after contrast-enhanced CT. This information underlines the need for a proper risk-reward assessment before denying patients a contrast-enhanced CT. KEY POINTS: • Iodine contrast media is considered a risk factor for the development of acute kidney injury. • Patients receiving iodine contra

Introduction: Acute kidney injury is an early-stage renal damage that can be detected by neutrophilic gelatinase-associated lipocalin protein. Aim: To evaluate the usefulness of neutrophilic gelatinase-associated lipocalin protein as an early marker of Acute Kidney Inju r y. Methodology: narrative review following the PRISMA statement criteria. PubMed, Scopus, and LILACS were the databases consulted. Results: 23 articles published in the last five years were identified. The evidence shows that this protein has biochemical characteristics useful in the early diagnosis of renal injury in different situations and populations. Discussion: The behavior of NGAL has demonstrated its increase in plasma up to 2 hours after the onset of renal impairment. Likewise, its synthesis is not affected by variables such as sex, body mass index, high protein intake, excess physical activity, and alteration in glomerular filtration, which do modify Crs concentrations. Conclusions: Neutrophilic gelatinase-associated lipocalin meets the criteria to become an early biomarker for Acute Kidney Introduction: Acute kidney injury is an early-stage renal damage that can be detected by neutrophilic gelatinase-associated lipocalin protein. Aim: To evaluate the usefulness of neutrophilic gelatinase-associated lipocalin protein as an early marker of Acute Kidney Inju r y. Methodology: narrative review following the PRISMA statement criteria. PubMed, Scopus, and LILACS were the databases consulted. Results: 23 articles published in the last five years were identified. The evidence shows that this protein has biochemical characteristics useful in the early diagnosis of renal injury in different situations and populations. Discussion: The behavior of NGAL has demonstrated its increase in plasma up to 2 hours after the onset of renal impairment. Likewise, its synthesis is not affected by variables such as sex, body mass index, high protein intake, excess physical activity, and alteration in glomerular f, Introducción: La lesión renal aguda es un daño renal en etapa temprana que, se postula, podría ser detectada por la proteína lipocalina asociada a gelatina neutrofílica. Objetivo: Evaluar la utilidad de la proteína lipocalina asociada a gelatina neutrofílica como marcador precoz de Lesión Renal Aguda. Metodología: revisión narrativa siguiendo los criterios de la declaración PRISMA. PubMed, Scopus y LILACS fueron las bases de datos consultadas. Resultados: se identificó un total de 23 artículos publicados en los últimos cinco años. Las evidencias muestran que esta proteína posee características bioquímicas útiles en el diagnóstico precoz de lesión renal en diferentes situaciones y poblaciones. Discusión:El comportamiento de NGAL ha demostrado su aumento en plasma hasta 2 horas después de iniciarse la deficiencia renal. Asimismo, su síntesis no se ve afectada por variables como el sexo, el índice de masa corporal, el alto consumo de proteína, el exceso de actividad física y la alteración en la filtración glomerular, que sí modifican las concentraciones de la Crs. Conclusiones: La lipocalina asociada a gelatinasa neutrofílica cumple con los criterios requeridos para convertirse en un biomarcador precoz para Lesión Renal Aguda.

We present the case of a 29-year-old woman, with a diagnosis of chronic kidney disease, systemic lupus erythematosus without lupus nephritis criteria, who developed SARS-COV-2 infection, and had acute kidney injury, requiring dialysis. Renal biopsy showed focal segmental glomerulosclerosis, perihilar variant, and evidence of advanced sclerosis. However, renal function recovered several months later, without immunosuppression, so the glomerular damage and acute kidney injury were considered to be secondary to the COVID-19 infection. Since focal and segmental glomerulosclerosis occurred in patients with COVID-19, but its association was infrequent in patients who also had systemic lupus erythematosus, this case is reported., Presentamos el caso de una mujer de 29 años con diagnóstico de enfermedad renal crónica, lupus eritematoso sistémico, sin criterios de nefritis lúpica, quien desarrolló infección por SARS–COV–2, y cursó con injuria renal aguda, requiriendo diálisis. La biopsia renal mostró glomeruloesclerosis focal y segmentaria, variante perihiliar y evidencia de esclerosis avanzada. Sin embargo, recuperó función renal varios meses después, sin inmunosupresión, por lo que se consideró que el daño glomerular y la injuria renal aguda fueron secundarios a la infección por COVID–19. Dado que la glomeruloesclerosis focal y segmentaria, se presentó en pacientes con COVID–19, pero fue infrecuente su asociación en pacientes que, además tuvieron lupus eritematoso sistémico, se reporta este caso.

Mannitol has been used for many years as an osmotic agent in the management of various medical conditions, including cerebral edema and glaucoma. However, its use has been associated with complications such as changes in blood volume and the internal milieu, leading to its progressive substitution by hypertonic saline solutions. In addition, it has been used to prevent and manage acute kidney injury, particularly in surgical patients, and to preserve diuresis in conditions that may promote acute tubular necrosis. Mannitol has also been used in hemodialysis patients to prevent and treat acute complications such as intradialytic hypotension, cramps, and dialysis disequilibrium syndrome. However, most of the studies are retrospective and of low power. Despite the known associated complications, mannitol continues to be used in many centers due to its availability and easy administration. This review aims to evaluate the efficacy and safety of mannitol in managing kidney diseases., El manitol ha sido utilizado por muchos años como agente osmótico en el manejo de diversas patologías, tales como edema cerebral y el glaucoma. Sin embargo, su uso se ha asociado a complicaciones, fundamentalmente alteraciones de la volemia y del medio interno, lo que ha llevado a sustituirlo progresivamente por soluciones salinas hipertónicas. Además, se ha usado para la prevención y manejo de la lesión renal aguda, particularmente en pacientes quirúrgicos y para preservar la diuresis en condiciones que pueden propiciar una necrosis tubular aguda. El manitol también se ha utilizado en pacientes en hemodiálisis para prevenir y tratar complicaciones agudas como hipotensión intradiálisis, calambres y el síndrome de desequilibrio. Aunque la mayoría de los estudios son retrospectivos y de bajo poder estadístico, y a pesar de las conocidas complicaciones asociadas, el manitol se sigue utilizando en muchos centros por su disponibilidad y fácil administración. La presente revisión tiene por objetivo evaluar la eficacia y la seguridad del manitol el tratamiento de las enfermedades renales.

Introduction and objectives: Contrast-induced-acute kidney injury (CI-AKI) is a potential complication of angiographic procedures. The DyeVert Contrast Reduction system (Osprey Medical, United States) is a device to reduce the concentration of contrast medium (CM) in the kidneys by decreasing the amount of CM delivered to patients. Unlike manual systems, few data are available on the DyeVert Power XT system, which is used in conjunction with automated contrast injection. The main aim of our study was to evaluate its effectiveness during percutaneous coronary interventions (PCI). Methods: Between 2020 and 2022, 101 patients who underwent PCI with the DyeVert Power XT system (case group) were enrolled to evaluate the amount of CM saved through the use of this device, as well as the rate, severity, and predictors of CI-AKI. Patients who underwent PCI without the use of the device (control group) were enrolled to create a matched group allowing assessment of differences in CM and the CI-AKI rate. Results: In the case group, the amount of CM saved was 114 ± 42 mL, representing an average of 32% of the total CM. Fourteen patients (13.9%) developed CI-AKI. The only independent predictors of CI-AKI were hematocrit (OR, 0.86; 95%CI, 0.74-0.99; P = .04) and ejection fraction (OR, 0.88; 95%CI, 0.82-0.95; P = .001). As a result of diversion by the device, the amount of CM delivered was lower in the case group than in controls (252 vs 267 mL; P = .42), but this difference was nonsignificant. Equally, the reduction in CI-AKI (14.3% vs 16.3%) was nonsignificant. Conclusions: Hematocrit and ejection fraction may be more important predictors of CI-AKI than the CM volume normally used during PCI in the general population. The net practical benefit of DyeVert Power XT was low., Introducción y objetivos: La nefropatía inducida por contraste (NIC) es una potencial complicación de los procedimientos angiográficos. El sistema DyeVert Power (Osprey Medical, Estados Unidos) permite reducir la concentración renal del medio de contraste al disminuir la cantidad administrada a los pacientes. Al contrario que sobre los sistemas manuales, existen pocos datos disponibles sobre el sistema DyeVert, que se utiliza junto a la inyección automática de contraste. El objetivo principal de este estudio fue evaluar su eficacia en procedimientos de intervencionismo coronario percutáneo (ICP). Métodos: Entre 2020 y 2022 se incluyó a 101 pacientes a quienes se realizó ICP utilizando el sistema DyeVert Power XT (grupo de casos) para evaluar la cantidad ahorrada de medio de contraste, así como la tasa, la gravedad y los predictores de NIC. Además, se seleccionó un grupo control de pacientes a los que se había realizado ICP sin utilizar el sistema DyeVert para comparar la cantidad de medio de contraste administrado y la tasa de NIC. Resultados: En el grupo de casos se redujo la administración de medio de contraste en 114 ± 42 ml (una media del 32% del total). Desarrollaron NIC 14 pacientes (13,9%). Los predictores de NIC fueron el hematocrito (OR = 0,86; IC95%: 0,74-0,99; p = 0,04) y la fracción de eyección (OR = 0,88; IC95%: 0,82-0,95; p = 0,001). Como resultado de la utilización del sistema DyeVert, la cantidad administrada de medio de contraste fue menor, pero sin diferencias estadísticamente significativas (252 frente a 267 ml; p = 0,42). La tasa de NIC fue menor con el sistema DyeVert, pero sin alcanzar la significación estadística (14,3 frente a 16,3%; p = 1,0). Conclusiones: El hematocrito y la fracción de eyección, más que la cantidad de contraste administrada, pueden ser predictores de NIC en los pacientes que reciben ICP. El beneficio del sistema DyeVert fue bajo.

BACKGROUND: To investigate the individual profile of each SGLT2 (sodium-glucose cotransoporter-2) inhibitor in patients with different backgrounds. METHODS AND RESULTS: This study included 21 placebo-controlled randomized controlled trials with a total of 96 196 participants, investigating empagliflozin, ertugliflozin, dapagliflozin, canagliflozin, and sotagliflozin. The primary efficacy end point was the composite of cardiovascular death and hospitalizations for heart failure. The secondary efficacy end points were all-cause death, cardiovascular death, hospitalizations for heart failure, kidney disease progression, and acute kidney injury. We conducted subgroup analyses based on the underlying comorbidities, including diabetes and chronic kidney disease. Safety end points were also assessed among SGLT2 inhibitors in the overall cohort. In the overall cohort, there were no significant differences in the primary efficacy outcome among the SGLT2 inhibitors, while empagliflozin (hazard ratio [HR], 0.70 [95% CI, 0.53-0.92]) and dapagliflozin (HR, 0.73 [95% CI, 0.56-0.96]) were associated with lower risk of acute kidney injury than sotagliflozin. The presence or absence of diabetes did not alter the results. In patients with chronic kidney disease, there were no differences in the efficacy outcomes among SGLT2 inhibitors, while in patients without chronic kidney disease, empagliflozin was associated with lower risk of the primary outcome compared with ertugliflozin (HR, 0.77 [95% CI, 0.60-0.98]). For safety outcomes, no significant differences were observed in amputation, urinary tract infection, genital infection, hypoglycemia, and diabetic ketoacidosis. CONCLUSIONS: The differences in reducing cardiovascular and kidney outcomes as well as safety profiles across SGLT2 inhibitors were not consistently significant, although empagliflozin might be preferred in patients without chronic kidney disease. Further investigations are needed to better understand the mechanism and

Maleic acid (MA) induces renal tubular cell dysfunction directed to acute kidney injury (AKI). AKI is an increasing global health burden due to its association with mortality and morbidity. However, targeted therapy for AKI is lacking. Previously, we determined mitochondrial-associated proteins are MA-induced AKI affinity proteins. We hypothesized that mitochondrial dysfunction in tubular epithelial cells plays a critical role in AKI. In vivo and in vitro systems have been used to test this hypothesis. For the in vivo model, C57BL/6 mice were intraperitoneally injected with 400 mg/kg body weight MA. For the in vitro model, HK-2 human proximal tubular epithelial cells were treated with 2 mM or 5 mM MA for 24 h. AKI can be induced by administration of MA. In the mice injected with MA, the levels of blood urea nitrogen (BUN) and creatinine in the sera were significantly increased (p < 0.005). From the pathological analysis, MA-induced AKI aggravated renal tubular injuries, increased kidney injury molecule-1 (KIM-1) expression and caused renal tubular cell apoptosis. At the cellular level, mitochondrial dysfunction was found with increasing mitochondrial reactive oxygen species (ROS) (p < 0.001), uncoupled mitochondrial respiration with decreasing electron transfer system activity (p < 0.001), and decreasing ATP production (p < 0.05). Under transmission electron microscope (TEM) examination, the cristae formation of mitochondria was defective in MA-induced AKI. To unveil the potential target in mitochondria, gene expression analysis revealed a significantly lower level of ATPase6 (p < 0.001). Renal mitochondrial protein levels of ATP subunits 5A1 and 5C1 (p < 0.05) were significantly decreased, as confirmed by protein analysis. Our study demonstrated that dysfunction of mitochondria resulting from altered expression of ATP synthase in renal tubular cells is associated with MA-induced AKI. This finding provides a potential novel targ

Introduction: Pregnancy-related acute kidney injury has a significant impact on maternal and fetal morbidity and mortality. General Objective: Identify the factors associated with fetal, maternal, and renal outcomes in pregnant women who develop acute kidney injury or exacerbation of chronic kidney disease. Materials and methods: Observational, descriptive, retrospective, cross-sectional study, cohort of pregnant women who have developed acute kidney injury or exacerbation of chronic kidney disease admitted to the Social Security Central Hospi- tal. Somatometric, demographic, and clinical data, days of hospitalization, and ob- stetric and biochemical data were collected at the beginning and end of pregnancy. Results: 90 patients, 30 years old (SD ± 5.51), normal BMI, Central Department, university student, GFR, and proteinuria (p<0.05). EHE, GD, pyelonephritis, fetal death 16%, cesarean section 71%. Conclusions: Fetal delivery is 16% in the studied population., Introducción: La lesión renal aguda relacionada con el embarazo tiene un impacto significativo en la morbilidad y mortalidad materna y fetal. Objetivo General: Identificar los factores asociados con los desenlaces fetales, maternos y renales en embarazadas que desarrollen lesión renal aguda o exacerbación de enfermedad renal crónica. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo, de corte transverso, cohorte de mujeres embarazadas que hayan desarrollado lesión renal aguda o exacerbación de enfermedad renal crónica internadas en el Hospital Central de la seguridad social. Se recabaron los datos somatométricos y demográficos, clínicos, días de internación, datos obstétricos y bioquímicos al inicio y al final del embarazo. Resultados: 90 pacientes, 30 años (DE ± 5,51), IMC normal, departamento Central, universitaria, TFG y proteinuria (p<0,05). EHE, DG, pielonefritis, óbito fetal 16%, cesárea 71%. Conclusiones: Óbito fetal 16% en la población estudiada. &nbsp

Introduction: Pregnancy-related acute kidney injury has a significant impact on maternal and fetal morbidity and mortality. General Objective: Identify the factors associated with fetal, maternal, and renal outcomes in pregnant women who develop acute kidney injury or exacerbation of chronic kidney disease. Materials and methods: Observational, descriptive, retrospective, cross-sectional study, cohort of pregnant women who have developed acute kidney injury or exacerbation of chronic kidney disease admitted to the Social Security Central Hospi- tal. Somatometric, demographic, and clinical data, days of hospitalization, and ob- stetric and biochemical data were collected at the beginning and end of pregnancy. Results: 90 patients, 30 years old (SD ± 5.51), normal BMI, Central Department, university student, GFR, and proteinuria (p<0.05). EHE, GD, pyelonephritis, fetal death 16%, cesarean section 71%. Conclusions: Fetal delivery is 16% in the studied population., Introducción: La lesión renal aguda relacionada con el embarazo tiene un impacto significativo en la morbilidad y mortalidad materna y fetal. Objetivo General: Identificar los factores asociados con los desenlaces fetales, maternos y renales en embarazadas que desarrollen lesión renal aguda o exacerbación de enfermedad renal crónica. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo, de corte transverso, cohorte de mujeres embarazadas que hayan desarrollado lesión renal aguda o exacerbación de enfermedad renal crónica internadas en el Hospital Central de la seguridad social. Se recabaron los datos somatométricos y demográficos, clínicos, días de internación, datos obstétricos y bioquímicos al inicio y al final del embarazo. Resultados: 90 pacientes, 30 años (DE ± 5,51), IMC normal, departamento Central, universitaria, TFG y proteinuria (p<0,05). EHE, DG, pielonefritis, óbito fetal 16%, cesárea 71%. Conclusiones: Óbito fetal 16% en la población estudiada. &nbsp

With the increasing incidence of kidney diseases, there is an urgent need to develop therapeutic strategies to combat post-injury fibrosis. Immune cells, including platelets, play a pivotal role in this repair process, primarily through their released cytokines. However, the specific role of platelets in kidney injury and subsequent repair remains underexplored. Here, the detrimental role of platelets in renal recovery following ischemia/reperfusion injury and its contribution to acute kidney injury  to chronic kidney disease transition is aimed to investigated. In this study, it is shown that depleting platelets accelerates injury resolution and significantly reduces fibrosis. Employing advanced single-cell and spatial transcriptomic techniques, macrophages as the primary mediators modulated by platelet signals is identified. A novel subset of macrophages, termed cycling M2, which exhibit an M2 phenotype combined with enhanced proliferative activity is uncovered. This subset emerges in the injured kidney during the resolution phase and is modulated by platelet-derived thrombospondin 1 (THBS1) signaling, acquiring profibrotic characteristics. Conversely, targeted inhibition of THBS1 markedly downregulates the cycling M2 macrophage, thereby mitigating fibrotic progression. Overall, this findings highlight the adverse role of platelet THBS1-boosted cycling M2 macrophages in renal injury repair and suggest platelet THBS1 as a promising therapeutic target for alleviating inflammation and kidney fibrosis.

PURPOSE: The development of acute kidney injury (AKI) after the acute respiratory distress syndrome (ARDS) reduces the chance of organ recovery and survival. The purpose of this study was to examine the AKI rate and attributable mortality in ARDS patients. METHODS: We performed an individual patient-data analysis including 10 multicenter randomized controlled trials conducted over 20 years. We employed a Super Learner ensemble technique, including a time-dependent analysis, to estimate the adjusted risk of AKI. We calculated the mortality attributable to AKI using an inverse probability of treatment weighting estimator integrated with the Super Learner. RESULTS: There were 5148 patients included in this study. The overall incidence of AKI was 43.7% (n = 2251). The adjusted risk of AKI ranged from 38.8% (95% confidence interval [CI], 35.7 to 41.9%) in ARMA, to 55.8% in ROSE (95% CI, 51.9 to 59.6%). 37.1% recovered rapidly from AKI, with a significantly lower recovery rate in recent trials (P < 0.001). The 90-day excess in mortality attributable to AKI was 15.4% (95% CI, 12.8 to 17.9%). It decreased from 25.4% in ARMA (95% CI, 18.7 to 32%), to 11.8% in FACTT (95% CI, 5.5 to 18%) and then remained rather stable over time. The 90-day overall excess in mortality attributable to acute kidney disease was 28.4% (95% CI, 25.3 to 31.5%). CONCLUSIONS: The incidence of AKI appears to be stable over time in patients with ARDS enrolled in randomized trials. The development of AKI remains a significant contributing factor to mortality. These estimates are essential for designing future clinical trials for AKI prevention or treatment.

PURPOSE: Patients with impaired renal function using medication that affects glomerular filtration rate are at increased risk of developing acute kidney injury (AKI) leading to hospital admissions. The risk increases during periods of dehydration due to diarrhoea, vomiting or fever (so-called "sick days"), or high environmental temperatures (heat wave). This study aims to gain insight into the characteristics and preventability of medication-related admissions for AKI and dehydration in elderly patients.METHODS: Retrospective case series study in patients aged ≥ 65 years with admission for acute kidney injury, dehydration or electrolyte imbalance related to dehydration that was defined as medication-related. General practitioner's (GP) patient records including medication history and hospital discharge letters were available. For each admission, patient and admission characteristics were collected to review the patient journey. A case-by-case assessment of preventability of hospital admissions was performed.RESULTS: In total, 75 admissions were included. Most prevalent comorbidities were hypertension, diabetes, and known impaired renal function. Diuretics and RAS-inhibitors were the most prevalent medication combination. Eighty percent of patients experienced non-acute onset of symptoms and 60% had contacted their GP within 2 weeks prior to admission. Around 40% (n = 29) of admissions were considered potentially preventable if pharmacotherapy had been timely and adequately adjusted.CONCLUSION: A substantial proportion of patients admitted with AKI or dehydration experience non-acute onset of symptoms and had contacted their GP within 2 weeks prior to admission. Timely adjusting of medication in these patients could have potentially prevented a considerable number of admissions.

Micronutrients (MN), i.e. trace elements and vitamins, are essential components of the diet in relatively small amounts in any form of nutrition, with special needs in critically ill patients. Critical illness is characterised by the presence of inflammation and oxidative stress. MNs are tightly involved in antioxidant and immune defences. In addition, some conditions, and treatments result in large losses of biological fluids containing MNs: therefore, acute renal injury requiring renal replacement therapy, acute intestinal failure, and major burns and trauma are at high risk of acute depletion of body stores, and of deficiency. MN requirements are increased above standard DRI. Blood level interpretation is complicated by inflammation: some biomarkers assist the status determination. Due to the acute challenges of critical illness, it of utmost importance to cover the needs to maintain the organism's endogenous immune and antioxidant defences, and capacity to repair tissues. Practical strategies are proposed.

Background: The aim of this retrospective cohort study was to develop and validate on multiple international datasets a real-time machine learning model able to accurately predict persistent acute kidney injury (AKI) in the intensive care unit (ICU). Methods: We selected adult patients admitted to ICU classified as AKI stage 2 or 3 as defined by the “Kidney Disease: Improving Global Outcomes” criteria. The primary endpoint was the ability to predict AKI stage 3 lasting for at least 72 h while in the ICU. An explainable tree regressor was trained and calibrated on two tertiary, urban, academic, single-center databases and externally validated on two multi-centers databases. Results: A total of 7759 ICU patients were enrolled for analysis. The incidence of persistent stage 3 AKI varied from 11 to 6% in the development and internal validation cohorts, respectively and 19% in external validation cohorts. The model achieved area under the receiver operating characteristic curve of 0.94 (95% CI 0.92–0.95) in the US external validation cohort and 0.85 (95% CI 0.83–0.88) in the Italian external validation cohort. Conclusions: A machine learning approach fed with the proper data pipeline can accurately predict onset of Persistent AKI Stage 3 during ICU patient stay in retrospective, multi-centric and international datasets. This model has the potential to improve management of AKI episodes in ICU if implemented in clinical practice., SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND: The aim of this experimental study was to elucidate whether different distances between central venous catheter tips can affect drug clearance during continuous renal replacement therapy (CRRT). Central venous catheters (CVCs) are widely used in intensive care patients for drug infusion. If a patient receives CRRT, a second central dialysis catheter (CDC) is required. Where to insert CVCs is directed by guidelines, but recommendations regarding how to place multiple catheters are scarce. There are indications that a drug infused in a CVC with the tip close to the tip of the CDC, could be directly aspirated into the dialysis machine, with a risk of increased clearance. However, studies on whether clearance is affected by different CVC and CDC tip positions, when the two catheters are in the same vessel, are few. METHODS: In this model with 18 piglets, gentamicin (GM) and vancomycin (VM) were infused through a CVC during CRRT. The CVC tip was placed in different positions in relation to the CDC tip from caudal, i.e., proximal to the heart, to cranial, i.e., distal to the heart. Serum and dialysate concentrations were sampled after approximately 30 min of CRRT at four different positions: when the CVC tip was 2 cm caudally (+ 2), at the same level (0), and at 2 (- 2) and 4 (- 4) cm cranially of the tip of the CDC. Clearance was calculated. A mixed linear model was performed, and level of significance was set to p < 0.05. RESULTS: Clearance of GM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 17.3 (5.2), 18.6 (7.4), 20.0 (16.2) and 26.2 (12.2) ml/min, respectively (p = 0.04). Clearance of VM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 16.2 (4.5), 14.7 (4.9), 19.0 (10.2) and 21.2 (11.4) ml/min, respectively (p = 0.02). CONCLUSIONS: The distance between CVC and CDC tips can affect drug clearance during CRRT. A cranial versus a caudal tip position of the CVC in relation to the tip of the CDC led to the highest clearance.

Acute kidney injury is common in intensive care. In this setting sepsis, by definition a dysregulated inflammatory response secondary to infection, is the most common cause. Sepsis associated acute kidney injury is in turn linked to worse outcome. The syndrome is considered to be the result of multiple mechanisms elicited by the inflammatory response and not merely hypoperfusion. COVID-19 has become an additional cause of acute kidney injury in critically ill patients. The present thesis focused on investigating contributing aspects of the inflammatory response in regard to acute kidney injury development in sepsis and COVID-19. The innate immune response recognizes invading pathogens through preserved molecular structures. When detected small and short-acting immunomodulatory molecules, cytokines, are produced shaping the reaction. Neutrophils are quickly mobilized. They engage in degranulation and expulsion of extracellular traps aiming at eradicating pathogens but may in doing so cause collateral tissue damage. Neutrophils are proposed contributors to renal dysfunction during sepsis and COVID-19. We investigated the effect of hydrocortisone, a glucocorticoid, on renal function and neutrophil infiltration in an ovine sepsis model with associated renal impairment. The observed reduction in glomerular filtration and tubular sodium transport efficiency during sepsis was ameliorated. Neutrophil infiltration which was observed post mortem in renal tissue was not reduced by hydrocortisone. The progression of organ dysfunction and by extension also acute kidney injury during severe COVID-19 was early on considered caused by a hyperinflammatory state. We analysed plasma cytokine concentrations in patients admitted to intensive care because of respiratory failure secondary to COVID-19. Only a moderate increase of theses mediators was found. The majority of the cytokines analysed were in turn associated with acute kidney injury development. Human neutrophil lipocalin is a n

Acute kidney injury (AKI) stands as a prevalent and economically burdensome condition worldwide, yet its complex molecular mechanisms remain incompletely understood. To address this gap, our study employs a multifaceted approach, combining mass spectrometry and RNA sequencing technologies, to elucidate the intricate molecular landscape underlying nephrotoxin-induced AKI in mice by cisplatin- and LPS-induced. By examining the protein and RNA expression profiles, we aimed to uncover novel insights into the pathogenesis of AKI and identify potential diagnostic and therapeutic targets. Our results demonstrate significant down-regulation of Slc34a1 and Slc34a3, shedding light on their crucial roles in AKI pathology and highlighting their promise as actionable targets for diagnosis and treatment. This comprehensive analysis not only enhances our understanding of AKI pathophysiology but also offers valuable avenues for the development of targeted interventions to mitigate its clinical impact. Significance: Nephrotoxicity acute kidney injury (AKI) is a common clinical condition whose pathogenesis is the process by which some drugs, chemicals or other factors cause damage to the kidneys, resulting in impaired kidney function. Although it has been proved that different nephrotoxic substances can affect the kidney through different pathways, whether they have a commonality has not been registered. Here, we combined transcriptomics and proteomics to study the molecular mechanism of LPS and cisplatin-induced nephrotoxic acute kidney injury finding that the down-regulation of Slc34a1 and Slc34a3 may be a critical link in nephrotoxic acute kidney injury, which can be used as a marker for its early diagnosis. © 2024 Elsevier B.V.

Acute kidney injury is common in intensive care. In this setting sepsis, by definition a dysregulated inflammatory response secondary to infection, is the most common cause. Sepsis associated acute kidney injury is in turn linked to worse outcome. The syndrome is considered to be the result of multiple mechanisms elicited by the inflammatory response and not merely hypoperfusion. COVID-19 has become an additional cause of acute kidney injury in critically ill patients. The present thesis focused on investigating contributing aspects of the inflammatory response in regard to acute kidney injury development in sepsis and COVID-19. The innate immune response recognizes invading pathogens through preserved molecular structures. When detected small and short-acting immunomodulatory molecules, cytokines, are produced shaping the reaction. Neutrophils are quickly mobilized. They engage in degranulation and expulsion of extracellular traps aiming at eradicating pathogens but may in doing so cause collateral tissue damage. Neutrophils are proposed contributors to renal dysfunction during sepsis and COVID-19. We investigated the effect of hydrocortisone, a glucocorticoid, on renal function and neutrophil infiltration in an ovine sepsis model with associated renal impairment. The observed reduction in glomerular filtration and tubular sodium transport efficiency during sepsis was ameliorated. Neutrophil infiltration which was observed post mortem in renal tissue was not reduced by hydrocortisone. The progression of organ dysfunction and by extension also acute kidney injury during severe COVID-19 was early on considered caused by a hyperinflammatory state. We analysed plasma cytokine concentrations in patients admitted to intensive care because of respiratory failure secondary to COVID-19. Only a moderate increase of theses mediators was found. The majority of the cytokines analysed were in turn associated with acute kidney injury development. Human neutrophil lipocalin is a n

Background: Acute kidney injury (AKI) in children is a critical condition influenced by diverse factors, including surgery, critical illness, and nephrotoxin exposure. It affects up to 50% of pediatric ICU admissions and has significant mortality implications, especially post-heart surgery and in the presence of inotropes or ventilation. Methods: The study adhered to PRISMA 2020 standards, examining English literature from 2014 to 2024. Result: Initially retrieving 360 articles from online databases (PubMed, SagePub, SpringerLink and Google Scholar) eight relevant papers were selected after three rounds of screening for full-text analysis. Conclusion: Pediatric renal injury, including acute kidney injury (AKI) and its long-term implications, presents a significant clinical challenge across diverse settings. Recent studies highlight varying AKI incidences and outcomes, underscoring the need for effective management strategies and long-term renal surveillance to mitigate mortality and chronic kidney disease risks.

Background: The relationship between Acute kidney injury (AKI) and CKD is complex, with chronic kidney disease (CKD) being a risk factor due to reduced renal reserve and stress-related issues. AKI can initiate or accelerate CKD development, leading to maladaptive repair mechanisms and a growing public health burden. This systematic review aims to analyze current evidence on the risk of CKD development after AKI based on literatures of the last 10 years. Methods: The study adhered to PRISMA 2020 standards, examining English literature from 2014 to 2024. It excluded editorials, reviews from the same journal, and submissions without a DOI. PubMed, SagePub, SpringerLink, and Google Scholar were utilized as literature sources. Result: Initially retrieving 360 articles from online databases (PubMed, SagePub, SpringerLink and Google Scholar) eight relevant papers were selected after three rounds of screening for full-text analysis. Conclusion: Acute kidney injury (AKI) is a precursor to chronic kidney disease (CKD), impacting long-term renal health. Even mild episodes contribute to sustained glomerular filtration rate reductions, suggesting incomplete recovery and a narrow intervention window for prevention.

Background: The relationship between Acute kidney injury (AKI) and CKD is complex, with chronic kidney disease (CKD) being a risk factor due to reduced renal reserve and stress-related issues. AKI can initiate or accelerate CKD development, leading to maladaptive repair mechanisms and a growing public health burden. This systematic review aims to analyze current evidence on the risk of CKD development after AKI based on literatures of the last 10 years. Methods: The study adhered to PRISMA 2020 standards, examining English literature from 2014 to 2024. It excluded editorials, reviews from the same journal, and submissions without a DOI. PubMed, SagePub, SpringerLink, and Google Scholar were utilized as literature sources. Result: Initially retrieving 360 articles from online databases (PubMed, SagePub, SpringerLink and Google Scholar) eight relevant papers were selected after three rounds of screening for full-text analysis. Conclusion: Acute kidney injury (AKI) is a precursor to chronic kidney disease (CKD), impacting long-term renal health. Even mild episodes contribute to sustained glomerular filtration rate reductions, suggesting incomplete recovery and a narrow intervention window for prevention.

Background: Acute kidney injury (AKI) in children is a critical condition influenced by diverse factors, including surgery, critical illness, and nephrotoxin exposure. It affects up to 50% of pediatric ICU admissions and has significant mortality implications, especially post-heart surgery and in the presence of inotropes or ventilation. Methods: The study adhered to PRISMA 2020 standards, examining English literature from 2014 to 2024. Result: Initially retrieving 360 articles from online databases (PubMed, SagePub, SpringerLink and Google Scholar) eight relevant papers were selected after three rounds of screening for full-text analysis. Conclusion: Pediatric renal injury, including acute kidney injury (AKI) and its long-term implications, presents a significant clinical challenge across diverse settings. Recent studies highlight varying AKI incidences and outcomes, underscoring the need for effective management strategies and long-term renal surveillance to mitigate mortality and chronic kidney disease risks.

BACKGROUND: The aim of this experimental study was to elucidate whether different distances between central venous catheter tips can affect drug clearance during continuous renal replacement therapy (CRRT). Central venous catheters (CVCs) are widely used in intensive care patients for drug infusion. If a patient receives CRRT, a second central dialysis catheter (CDC) is required. Where to insert CVCs is directed by guidelines, but recommendations regarding how to place multiple catheters are scarce. There are indications that a drug infused in a CVC with the tip close to the tip of the CDC, could be directly aspirated into the dialysis machine, with a risk of increased clearance. However, studies on whether clearance is affected by different CVC and CDC tip positions, when the two catheters are in the same vessel, are few. METHODS: In this model with 18 piglets, gentamicin (GM) and vancomycin (VM) were infused through a CVC during CRRT. The CVC tip was placed in different positions in relation to the CDC tip from caudal, i.e., proximal to the heart, to cranial, i.e., distal to the heart. Serum and dialysate concentrations were sampled after approximately 30 min of CRRT at four different positions: when the CVC tip was 2 cm caudally (+ 2), at the same level (0), and at 2 (- 2) and 4 (- 4) cm cranially of the tip of the CDC. Clearance was calculated. A mixed linear model was performed, and level of significance was set to p < 0.05. RESULTS: Clearance of GM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 17.3 (5.2), 18.6 (7.4), 20.0 (16.2) and 26.2 (12.2) ml/min, respectively (p = 0.04). Clearance of VM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 16.2 (4.5), 14.7 (4.9), 19.0 (10.2) and 21.2 (11.4) ml/min, respectively (p = 0.02). CONCLUSIONS: The distance between CVC and CDC tips can affect drug clearance during CRRT. A cranial versus a caudal tip position of the CVC in relation to the tip of the CDC led to the highest clearance.

Introduction: The study objective was to investigate whether a Ringer’s acetate based priming solution with addition of Mannitol and sodium concentrate increases the risk of cardiac surgery associated kidney injury (CSA-AKI). Methods: This is a double blind, prospective randomized controlled trial from a single tertiary teaching hospital in Sweden including patients aged ≥65 years (n = 195) admitted for routine cardiac surgery with cardiopulmonary bypass. Patients in the study group received Ringer’s acetate 1000 mL + 400 mL Mannitol (60 g) + sodium chloride 40 mL (160 mmol) and heparin 2 mL (10 000 IU) 966 mOsmol (n = 98), while patients in the control group received Ringer’s acetate 1400 mL + heparin 2 mL (10 000 IU), 388 mOsmol (n = 97) as pump prime. Acute kidney injury was analysed based on the Kidney Disease Improving Outcomes (KDIGO 1-3) definition. Results: The overall incidence of CSA-AKI (KDIGO stage 1) was 2.6% on day 1 in the ICU and 5.6% on day 3, postoperatively. The serum creatinine level did not show any postoperative intergroup differences, when compared to baseline preoperative values. Six patients in the Ringer and five patients in the Mannitol group developed CSA-AKI (KDIGO 1-3), all with glomerular filtration rates <60 mL/min/1.73 m2. These patients showed significantly higher plasma osmolality levels compared to preoperative values. Hyperosmolality together with patient age and the duration of the surgery were independent risk factors for postoperative acute kidney injury (KDIGO 1-3). Conclusions: The use of a hyperosmolar prime solution did not increase the incidence of postoperative CSA-AKI in this study, while high plasma osmolality alone increased the associated risk by 30%. The data suggests further examination of plasma hyperosmolality as a relative risk factor of CSA-AKI.

Acute kidney injury is common in intensive care. In this setting sepsis, by definition a dysregulated inflammatory response secondary to infection, is the most common cause. Sepsis associated acute kidney injury is in turn linked to worse outcome. The syndrome is considered to be the result of multiple mechanisms elicited by the inflammatory response and not merely hypoperfusion. COVID-19 has become an additional cause of acute kidney injury in critically ill patients. The present thesis focused on investigating contributing aspects of the inflammatory response in regard to acute kidney injury development in sepsis and COVID-19. The innate immune response recognizes invading pathogens through preserved molecular structures. When detected small and short-acting immunomodulatory molecules, cytokines, are produced shaping the reaction. Neutrophils are quickly mobilized. They engage in degranulation and expulsion of extracellular traps aiming at eradicating pathogens but may in doing so cause collateral tissue damage. Neutrophils are proposed contributors to renal dysfunction during sepsis and COVID-19. We investigated the effect of hydrocortisone, a glucocorticoid, on renal function and neutrophil infiltration in an ovine sepsis model with associated renal impairment. The observed reduction in glomerular filtration and tubular sodium transport efficiency during sepsis was ameliorated. Neutrophil infiltration which was observed post mortem in renal tissue was not reduced by hydrocortisone. The progression of organ dysfunction and by extension also acute kidney injury during severe COVID-19 was early on considered caused by a hyperinflammatory state. We analysed plasma cytokine concentrations in patients admitted to intensive care because of respiratory failure secondary to COVID-19. Only a moderate increase of theses mediators was found. The majority of the cytokines analysed were in turn associated with acute kidney injury development. Human neutrophil lipocalin is a n

BACKGROUND: The aim of this experimental study was to elucidate whether different distances between central venous catheter tips can affect drug clearance during continuous renal replacement therapy (CRRT). Central venous catheters (CVCs) are widely used in intensive care patients for drug infusion. If a patient receives CRRT, a second central dialysis catheter (CDC) is required. Where to insert CVCs is directed by guidelines, but recommendations regarding how to place multiple catheters are scarce. There are indications that a drug infused in a CVC with the tip close to the tip of the CDC, could be directly aspirated into the dialysis machine, with a risk of increased clearance. However, studies on whether clearance is affected by different CVC and CDC tip positions, when the two catheters are in the same vessel, are few. METHODS: In this model with 18 piglets, gentamicin (GM) and vancomycin (VM) were infused through a CVC during CRRT. The CVC tip was placed in different positions in relation to the CDC tip from caudal, i.e., proximal to the heart, to cranial, i.e., distal to the heart. Serum and dialysate concentrations were sampled after approximately 30 min of CRRT at four different positions: when the CVC tip was 2 cm caudally (+ 2), at the same level (0), and at 2 (- 2) and 4 (- 4) cm cranially of the tip of the CDC. Clearance was calculated. A mixed linear model was performed, and level of significance was set to p < 0.05. RESULTS: Clearance of GM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 17.3 (5.2), 18.6 (7.4), 20.0 (16.2) and 26.2 (12.2) ml/min, respectively (p = 0.04). Clearance of VM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 16.2 (4.5), 14.7 (4.9), 19.0 (10.2) and 21.2 (11.4) ml/min, respectively (p = 0.02). CONCLUSIONS: The distance between CVC and CDC tips can affect drug clearance during CRRT. A cranial versus a caudal tip position of the CVC in relation to the tip of the CDC led to the highest clearance.

BACKGROUND: The aim of this experimental study was to elucidate whether different distances between central venous catheter tips can affect drug clearance during continuous renal replacement therapy (CRRT). Central venous catheters (CVCs) are widely used in intensive care patients for drug infusion. If a patient receives CRRT, a second central dialysis catheter (CDC) is required. Where to insert CVCs is directed by guidelines, but recommendations regarding how to place multiple catheters are scarce. There are indications that a drug infused in a CVC with the tip close to the tip of the CDC, could be directly aspirated into the dialysis machine, with a risk of increased clearance. However, studies on whether clearance is affected by different CVC and CDC tip positions, when the two catheters are in the same vessel, are few. METHODS: In this model with 18 piglets, gentamicin (GM) and vancomycin (VM) were infused through a CVC during CRRT. The CVC tip was placed in different positions in relation to the CDC tip from caudal, i.e., proximal to the heart, to cranial, i.e., distal to the heart. Serum and dialysate concentrations were sampled after approximately 30 min of CRRT at four different positions: when the CVC tip was 2 cm caudally (+ 2), at the same level (0), and at 2 (- 2) and 4 (- 4) cm cranially of the tip of the CDC. Clearance was calculated. A mixed linear model was performed, and level of significance was set to p < 0.05. RESULTS: Clearance of GM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 17.3 (5.2), 18.6 (7.4), 20.0 (16.2) and 26.2 (12.2) ml/min, respectively (p = 0.04). Clearance of VM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 16.2 (4.5), 14.7 (4.9), 19.0 (10.2) and 21.2 (11.4) ml/min, respectively (p = 0.02). CONCLUSIONS: The distance between CVC and CDC tips can affect drug clearance during CRRT. A cranial versus a caudal tip position of the CVC in relation to the tip of the CDC led to the highest clearance.

Introduction: The study objective was to investigate whether a Ringer’s acetate based priming solution with addition of Mannitol and sodium concentrate increases the risk of cardiac surgery associated kidney injury (CSA-AKI). Methods: This is a double blind, prospective randomized controlled trial from a single tertiary teaching hospital in Sweden including patients aged ≥65 years (n = 195) admitted for routine cardiac surgery with cardiopulmonary bypass. Patients in the study group received Ringer’s acetate 1000 mL + 400 mL Mannitol (60 g) + sodium chloride 40 mL (160 mmol) and heparin 2 mL (10 000 IU) 966 mOsmol (n = 98), while patients in the control group received Ringer’s acetate 1400 mL + heparin 2 mL (10 000 IU), 388 mOsmol (n = 97) as pump prime. Acute kidney injury was analysed based on the Kidney Disease Improving Outcomes (KDIGO 1-3) definition. Results: The overall incidence of CSA-AKI (KDIGO stage 1) was 2.6% on day 1 in the ICU and 5.6% on day 3, postoperatively. The serum creatinine level did not show any postoperative intergroup differences, when compared to baseline preoperative values. Six patients in the Ringer and five patients in the Mannitol group developed CSA-AKI (KDIGO 1-3), all with glomerular filtration rates <60 mL/min/1.73 m2. These patients showed significantly higher plasma osmolality levels compared to preoperative values. Hyperosmolality together with patient age and the duration of the surgery were independent risk factors for postoperative acute kidney injury (KDIGO 1-3). Conclusions: The use of a hyperosmolar prime solution did not increase the incidence of postoperative CSA-AKI in this study, while high plasma osmolality alone increased the associated risk by 30%. The data suggests further examination of plasma hyperosmolality as a relative risk factor of CSA-AKI.

Background: Agricultural workers in Mexico endure physically demanding work in a hot environment, increasing the risk for kidney injury and impaired kidney function. They are also exposed to nephrotoxic metal(loid)s such as arsenic, cadmium, chromium, lead, mercury, nickel, and uranium from natural and anthropogenic sources. However, few studies have investigated how combined exposures of heat and metal(loid)s impact kidney injury and functioning. Objectives: To fill this research gap, we assessed the combined effects of exposure to metal(loid)s and heat on acute kidney injury (AKI) and kidney function over time. Methods: Biological samples, anthropometric measurements, and questionnaires were collected from a cohort of adult males working at a Sonoran grape farm and a control group of non-farmworkers in a nearby city. Acute heat strain was assessed using inner ear temperature and heart rate to calculate the physiological strain index (PSI). Urine samples were analyzed for toxic metal(loid)s, specific gravity, and neutrophil gelatinase-associated lipocalin (uNGAL), while blood samples were analyzed for creatinine levels to calculate estimated glomerular filtration rate (eGFR). Descriptive statistics were computed, linear regression models were used to assess the relationship between socioeconomic variables and metal exposure, and linear mixed effect (LME) and linear regression models were used to evaluate the impact of metal(loid)s and PSI on kidney injury and function. Additionally, we examined an interaction term between each metal(loid) and sampling period as well as each metal(loid) and acute heat (PSI) in each of the LME models. Results: Agricultural workers reported lower education rates (93.5% < high school vs. 19%) and pay (69% less than $100USD/month vs. 0%), higher rates of migration for work (100% vs. 24%), and a greater proportion of Indigenous language speakers (27% vs. 4.8%) compared to non-agricultural workers. Creatinine-adjusted uNGAL levels among a

Background: Lung perfusion defects, mainly due to endothelial and coagulation activation, are a key contributor to COVID-19 respiratory failure. COVID-19 patients may also develop acute kidney injury (AKI) because of renal perfusion deficit. We aimed to explore AKI-associated factors and the independent prediction of standardized minute ventilation (MV)—a proxy of alveolar dead space—on AKI onset and persistence in COVID-19 mechanically ventilated patients. Methods: This is a multicenter observational cohort study. We enrolled 157 COVID-19 patients requiring mechanical ventilation and intensive care unit (ICU) admission. We collected clinical information, ventilation, and laboratory data. AKI was defined by the 2012 KDIGO guidelines and classified as transient or persistent according to serum creatinine criteria persistence within 48 h. Ordered univariate and multivariate logistic regression analyses were employed to identify variables associated with AKI onset and persistence. Results: Among 157 COVID-19 patients on mechanical ventilation, 47% developed AKI: 10% had transient AKI, and 37% had persistent AKI. The degree of hypoxia was not associated with differences in AKI severity. Across increasing severity of AKI groups, despite similar levels of paCO2, we observed an increased MV and standardized MV, a robust proxy of alveolar dead space. After adjusting for other clinical and laboratory covariates, standardized MV remained an independent predictor of AKI development and persistence. d-dimer levels were higher in patients with persistent AKI. Conclusions: In critically ill COVID-19 patients with respiratory failure, increased wasted ventilation is independently associated with a greater risk of persistent AKI. These hypothesis-generating findings may suggest that perfusion derangements may link the pathophysiology of both wasted ventilation and acute kidney injury in our population.

Acute kidney injury is common in intensive care. In this setting sepsis, by definition a dysregulated inflammatory response secondary to infection, is the most common cause. Sepsis associated acute kidney injury is in turn linked to worse outcome. The syndrome is considered to be the result of multiple mechanisms elicited by the inflammatory response and not merely hypoperfusion. COVID-19 has become an additional cause of acute kidney injury in critically ill patients. The present thesis focused on investigating contributing aspects of the inflammatory response in regard to acute kidney injury development in sepsis and COVID-19. The innate immune response recognizes invading pathogens through preserved molecular structures. When detected small and short-acting immunomodulatory molecules, cytokines, are produced shaping the reaction. Neutrophils are quickly mobilized. They engage in degranulation and expulsion of extracellular traps aiming at eradicating pathogens but may in doing so cause collateral tissue damage. Neutrophils are proposed contributors to renal dysfunction during sepsis and COVID-19. We investigated the effect of hydrocortisone, a glucocorticoid, on renal function and neutrophil infiltration in an ovine sepsis model with associated renal impairment. The observed reduction in glomerular filtration and tubular sodium transport efficiency during sepsis was ameliorated. Neutrophil infiltration which was observed post mortem in renal tissue was not reduced by hydrocortisone. The progression of organ dysfunction and by extension also acute kidney injury during severe COVID-19 was early on considered caused by a hyperinflammatory state. We analysed plasma cytokine concentrations in patients admitted to intensive care because of respiratory failure secondary to COVID-19. Only a moderate increase of theses mediators was found. The majority of the cytokines analysed were in turn associated with acute kidney injury development. Human neutrophil lipocalin is a n

BACKGROUND: The aim of this experimental study was to elucidate whether different distances between central venous catheter tips can affect drug clearance during continuous renal replacement therapy (CRRT). Central venous catheters (CVCs) are widely used in intensive care patients for drug infusion. If a patient receives CRRT, a second central dialysis catheter (CDC) is required. Where to insert CVCs is directed by guidelines, but recommendations regarding how to place multiple catheters are scarce. There are indications that a drug infused in a CVC with the tip close to the tip of the CDC, could be directly aspirated into the dialysis machine, with a risk of increased clearance. However, studies on whether clearance is affected by different CVC and CDC tip positions, when the two catheters are in the same vessel, are few. METHODS: In this model with 18 piglets, gentamicin (GM) and vancomycin (VM) were infused through a CVC during CRRT. The CVC tip was placed in different positions in relation to the CDC tip from caudal, i.e., proximal to the heart, to cranial, i.e., distal to the heart. Serum and dialysate concentrations were sampled after approximately 30 min of CRRT at four different positions: when the CVC tip was 2 cm caudally (+ 2), at the same level (0), and at 2 (- 2) and 4 (- 4) cm cranially of the tip of the CDC. Clearance was calculated. A mixed linear model was performed, and level of significance was set to p < 0.05. RESULTS: Clearance of GM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 17.3 (5.2), 18.6 (7.4), 20.0 (16.2) and 26.2 (12.2) ml/min, respectively (p = 0.04). Clearance of VM had median values at + 2 cm, 0 cm, - 2 cm and - 4 cm of 16.2 (4.5), 14.7 (4.9), 19.0 (10.2) and 21.2 (11.4) ml/min, respectively (p = 0.02). CONCLUSIONS: The distance between CVC and CDC tips can affect drug clearance during CRRT. A cranial versus a caudal tip position of the CVC in relation to the tip of the CDC led to the highest clearance.

The outcome for patients with sepsis-associated acute kidney injury in the intensive care unit (ICU) remains poor. Low serum uromodulin (sUMOD) protein levels have been proposed as a causal mediator of this effect. We investigated the effect of different levels of sUMOD on the risk of sepsis and severe pneumonia and outcomes in these conditions. A two-sample Mendelian randomization (MR) study was performed. Single-nucleotide polymorphisms (SNPs) associated with increased levels of sUMOD were identified and used as instrumental variables for association with outcomes. Data from different cohorts were combined based on disease severity and meta-analyzed. Five SNPs associated with increased sUMOD levels were identified and tested in six datasets from two biobanks. There was no protective effect of increased levels of sUMOD on the risk of sepsis [two cohorts, odds ratio (OR) 0.99 (95% confidence interval 0.95-1.03), P = 0.698, and OR 0.95 (0.91-1.00), P = 0.060, respectively], risk of sepsis requiring ICU admission [OR 1.04 (0.93-1.16), P = 0.467], ICU mortality in sepsis [OR 1.00 (0.74-1.37), P = 0.987], risk of pneumonia requiring ICU admission [OR 1.05 (0.98-1.14), P = 0.181], or ICU mortality in pneumonia [OR 1.17 (0.98-1.39), P = 0.079]. Meta-analysis of hospital-admitted and ICU-admitted patients separately yielded similar results [OR 0.98 (0.95-1.01), P = 0.23, and OR 1.05 (0.99-1.12), P = 0.86, respectively]. Among patients with sepsis and severe pneumonia, there was no protective effect of different levels of sUMOD. Results were consistent regardless of geographic origins and not modified by disease severity.

Background Hyperuricemia contributes to decrease in kidney function and induces additional renal damage in children with acute kidney injury (AKI). Rasburicase oxidizes uric acid (UA), decreasing its serum quantities in less than 24 h. Methods This is a retrospective study involving hospitalized patients under 18 years of age with underlying pathology diagnosed with AKI and severe hyperuricemia treated with rasburicase over a 4-year period. Results We describe 15 patients from 4 days of life to 18 years (median: 4.4 years). Seventy-three percent had known underlying pathologies. All presented worsening of basal renal function or AKI data. All received the usual medical treatment for AKI without response. Twenty percent received an extrarenal depuration technique. All had hyperuricemia with a mean (± SD) of 13.1 (± 2.19) mg/dl. After rasburicase administration UA levels fell to a mean (± SD) of 0.76 (± 0.62) mg/dl (p < 0.001) in less than 24 h. In parallel, a decrease in the mean plasma creatinine was observed (2.92 mg/dl to 1.93 mg/dl (p = 0.057)) together with a significant improvement of the mean glomerular filtration rate (16.3 ml/min/1.73 m2 to 78.6 ml/min/1.73 m2) (p = 0.001)). No side effects were recorded. Kidney function normalized in all cases or returned to baseline levels. Conclusions Although the use of rasburicase is not routinely approved in pediatric patients with severe hyperuricemia and AKI, it has been used successfully without complications, and helped prevent progressive kidney damage. This study could serve as a basis for suggesting the off-label use of rasburicase for the management of complex pediatric patients in whom UA plays an important role in the development of AKI.

BACKGROUND: Indomethacin is administered as a tocolytic agent for threatening preterm labor <28weeks of gestation. Only a few, not conclusive, studies have investigated its nephrotoxicity in very low birth weight (VLBW) infants. We investigated whether indomethacin increases the incidence of acute kidney injury (AKI) among VLBW infants. METHODS: This is a retrospective study including all VLBW infants born at our center between January 1, 2005, and December 31, 2013. Indomethacin was administered to women with preterm labor and intact membranes. Neonatal AKI was defined according to KDIGO classification. Univariate analyses were performed comparing VLBW infants exposed to and not exposed to indomethacin. In the multivariable model, the association of indomethacin and AKI was adjusted for patent ductus arteriosus, use of nephrotoxic medications, birth weight, and gestational age. RESULTS: Five hundred seventy-five VLBW infants were included, 49 (8.5%) of whom were exposed to indomethacin in utero. The univariate analysis showed that infants exposed to indomethacin had lower birth weight, lower gestational age, and higher incidence of AKI than infants not exposed. The multivariable model adjusted for confounding factors confirmed an increased risk of AKI in relation to gestational age at birth <27 weeks, but not to indomethacin. CONCLUSIONS: Our data suggest that extreme prematurity, but not the use of indomethacin, is associated with AKI.

BACKGROUND: Esophagectomy is a complex oncologic operation associated with high rates of postoperative complications. While respiratory and septic complications have been well-defined, the implications of acute kidney injury (AKI) remain unclear. Using a nationally representative database, we aimed to characterize the association of AKI with mortality, resource use, and 30-day readmission. METHODS: All adults undergoing elective esophagectomy with a diagnosis of esophageal or gastric cancer were identified in the 2010-2019 Nationwide Readmissions Database. Study cohorts were stratified based on presence of AKI. Multivariable regressions and Royston-Parmar survival analysis were used to evaluate the independent association between AKI and outcomes of interest. RESULTS: Of an estimated 40,438 patients, 3,210 (7.9%) developed AKI. Over the 10-year study period, the incidence of AKI increased from 6.4% to 9.7%. Prior radiation/chemotherapy and minimally invasive operations were associated with reduced odds of AKI, whereas public insurance coverage and concurrent infectious and respiratory complications had greater risk of AKI. After risk adjustment, AKI remained independently associated with greater odds of in-hospital mortality (AOR: 4.59, 95% CI: 3.62-5.83) and had significantly increased attributable costs ($112,000 vs $54,000) and length of stay (25.7 vs 13.3 days) compared to patients without AKI. Furthermore, AKI demonstrated significantly increased hazard of 30-day readmission (hazard ratio: 1.16, 95% CI: 1.01-1.32). CONCLUSIONS: AKI after esophagectomy is associated with greater risk of mortality, hospitalization costs, and 30-day readmission. Given the significant adverse consequences of AKI, careful perioperative management to mitigate this complication may improve quality of esophageal surgical care at the national level.

Acute kidney injury (AKI) often complicates sepsis and is associated with high morbidity and mortality. In recent years, several important clinical trials have improved our understanding of sepsis-associated AKI (SA-AKI) and impacted clinical care. Advances in sub-phenotyping of sepsis and AKI and clinical trial design offer unprecedented opportunities to fill gaps in knowledge and generate better evidence for improving the outcome of critically ill patients with SA-AKI. In this manuscript, we review the recent literature of clinical trials in sepsis with focus on studies that explore SA-AKI as a primary or secondary outcome. We discuss lessons learned and potential opportunities to improve the design of clinical trials and generate actionable evidence in future research. We specifically discuss the role of enrichment strategies to target populations that are most likely to derive benefit and the importance of patient-centered clinical trial endpoints and appropriate trial designs with the aim to provide guidance in designing future trials.

Acute kidney injury (AKI) following hyperthermic intraperitoneal chemotherapy (HIPEC) is common. Identifying patients at risk could have implications for surgical and anesthetic management. We aimed to develop a predictive model that could predict AKI based on patients preoperative characteristics and intraperitoneal chemotherapy regimen. We retrospectively gathered data of adult patients undergoing HIPEC at our health system between November 2013 and April 2022. Next, we developed a model predicting postoperative AKI using multivariable logistic regression and calculated the performance of the model (area under the receiver operating characteristics curve [AUC]) via tenfold cross-validation. A total of 412 patients were included, of which 36 (8.7%) developed postoperative AKI. Based on our multivariable logistic regression model, multiple preoperative and intraoperative characteristics were associated with AKI. We included the total intraoperative cisplatin dose, body mass index, male sex, and preoperative hemoglobin level in the final model. The mean area under the receiver operating characteristics curve value was 0.82 (95% confidence interval 0.71-0.93). Our risk model predicted AKI with high accuracy in patients undergoing HIPEC in our institution. The external validity of our model should now be tested in independent and prospective patient cohorts.

Introduction: The study objective was to investigate whether a Ringer’s acetate based priming solution with addition of Mannitol and sodium concentrate increases the risk of cardiac surgery associated kidney injury (CSA-AKI). Methods: This is a double blind, prospective randomized controlled trial from a single tertiary teaching hospital in Sweden including patients aged ≥65 years (n = 195) admitted for routine cardiac surgery with cardiopulmonary bypass. Patients in the study group received Ringer’s acetate 1000 mL + 400 mL Mannitol (60 g) + sodium chloride 40 mL (160 mmol) and heparin 2 mL (10 000 IU) 966 mOsmol (n = 98), while patients in the control group received Ringer’s acetate 1400 mL + heparin 2 mL (10 000 IU), 388 mOsmol (n = 97) as pump prime. Acute kidney injury was analysed based on the Kidney Disease Improving Outcomes (KDIGO 1-3) definition. Results: The overall incidence of CSA-AKI (KDIGO stage 1) was 2.6% on day 1 in the ICU and 5.6% on day 3, postoperatively. The serum creatinine level did not show any postoperative intergroup differences, when compared to baseline preoperative values. Six patients in the Ringer and five patients in the Mannitol group developed CSA-AKI (KDIGO 1-3), all with glomerular filtration rates <60 mL/min/1.73 m2. These patients showed significantly higher plasma osmolality levels compared to preoperative values. Hyperosmolality together with patient age and the duration of the surgery were independent risk factors for postoperative acute kidney injury (KDIGO 1-3). Conclusions: The use of a hyperosmolar prime solution did not increase the incidence of postoperative CSA-AKI in this study, while high plasma osmolality alone increased the associated risk by 30%. The data suggests further examination of plasma hyperosmolality as a relative risk factor of CSA-AKI.

Backgrounds/Aims: Optimal intravenous fluid management during the perioperative period for patients undergoing pancreaticoduodenectomy (PD) within the framework of enhanced recovery after surgery (ERAS) is unclear. Studies have indicated that excessive total body salt and water can contribute to the development of oedema, leading to increased morbidity and extended hospital stays. This study aimed to assess the effects of an intravenous therapy regimen during postoperative day (POD) 0 to 2 in PD patients within ERAS. Methods: A retrospective interventional cohort study was conducted, and it involved all PD patients before and after implementation of ERAS (2009–2017). In the ERAS group, a targeted maintenance fluid regimen of 20 mL/kg/day with a sodium requirement of 0.5 mmoL/kg/day was administered. Outcome measures included the mmol of sodium and chloride administered, length of stay, and morbidity (postoperative pancreatic fistula, POPF; acute kidney injury, AKI; ileus). Results: The study included 169 patients, with a mean age of 64 ± 11.3 years. Following implementation of the intravenous fluid therapy protocol, there was a significant reduction in chloride and sodium loading. However, in the multivariable analysis, chloride administered (mmoL/kg) did not independently influence the length of stay; or rates of POPF, ileus, or AKI (p > 0.05). Conclusions: The findings suggested that a postoperative intravenous fluid therapy regimen did not significantly impact morbidity. Notably, there was a trend towards reduced length of stay within an increasingly comorbid patient cohort. This targeted fluid regimen appears to be safe for PD patients within the ERAS program. Further prospective research is needed to explore this area.

Purpose: Ilofotase alfa is a human recombinant alkaline phosphatase with reno-protective effects that showed improved survival and reduced Major Adverse Kidney Events by 90 days (MAKE90) in sepsis-associated acute kidney injury (SA-AKI) patients. REVIVAL, was a phase-3 trial conducted to confirm its efficacy and safety. Methods: In this international double-blinded randomized-controlled trial, SA-AKI patients were enrolled < 72 h on vasopressor and < 24 h of AKI. The primary endpoint was 28-day all-cause mortality. The main secondary endpoint was MAKE90, other secondary endpoints were (i) days alive and free of organ support through day 28, (ii) days alive and out of the intensive care unit (ICU) through day 28, and (iii) time to death through day 90. Prior to unblinding, the statistical analysis plan was amended, including an updated MAKE90 definition. Results: Six hundred fifty patients were treated and analyzed for safety; and 649 for efficacy data (ilofotase alfa n = 330; placebo n = 319). The observed mortality rates in the ilofotase alfa and placebo groups were 27.9% and 27.9% at 28 days, and 33.9% and 34.8% at 90 days. The trial was stopped for futility on the primary endpoint. The observed proportion of patients with MAKE90A and MAKE90B were 56.7% and 37.4% in the ilofotase alfa group vs. 64.6% and 42.8% in the placebo group. Median [interquartile range (IQR)] days alive and free of organ support were 17 [0–24] and 14 [0–24], number of days alive and discharged from the ICU through day 28 were 15 [0–22] and 10 [0–22] in the ilofotase alfa and placebo groups, respectively. Adverse events were reported in 67.9% and 75% patients in the ilofotase and placebo group. Conclusion: Among critically ill patients with SA-AKI, ilofotase alfa did not improve day 28 survival. There may, however, be reduced MAKE90 events. No safety concerns were identified.

Introduction: The study objective was to investigate whether a Ringer’s acetate based priming solution with addition of Mannitol and sodium concentrate increases the risk of cardiac surgery associated kidney injury (CSA-AKI). Methods: This is a double blind, prospective randomized controlled trial from a single tertiary teaching hospital in Sweden including patients aged ≥65 years (n = 195) admitted for routine cardiac surgery with cardiopulmonary bypass. Patients in the study group received Ringer’s acetate 1000 mL + 400 mL Mannitol (60 g) + sodium chloride 40 mL (160 mmol) and heparin 2 mL (10 000 IU) 966 mOsmol (n = 98), while patients in the control group received Ringer’s acetate 1400 mL + heparin 2 mL (10 000 IU), 388 mOsmol (n = 97) as pump prime. Acute kidney injury was analysed based on the Kidney Disease Improving Outcomes (KDIGO 1-3) definition. Results: The overall incidence of CSA-AKI (KDIGO stage 1) was 2.6% on day 1 in the ICU and 5.6% on day 3, postoperatively. The serum creatinine level did not show any postoperative intergroup differences, when compared to baseline preoperative values. Six patients in the Ringer and five patients in the Mannitol group developed CSA-AKI (KDIGO 1-3), all with glomerular filtration rates <60 mL/min/1.73 m2. These patients showed significantly higher plasma osmolality levels compared to preoperative values. Hyperosmolality together with patient age and the duration of the surgery were independent risk factors for postoperative acute kidney injury (KDIGO 1-3). Conclusions: The use of a hyperosmolar prime solution did not increase the incidence of postoperative CSA-AKI in this study, while high plasma osmolality alone increased the associated risk by 30%. The data suggests further examination of plasma hyperosmolality as a relative risk factor of CSA-AKI.

Background: Acute kidney injury (AKI) represents a significant global health challenge, leading to increased patient distress and financial health care burdens. The development of AKI in intensive care unit (ICU) settings is linked to prolonged ICU stays, a heightened risk of long-term renal dysfunction, and elevated short-and long-term mortality rates. The current diagnostic approach for AKI is based on late indicators, such as elevated serum creatinine and decreased urine output, which can only detect AKI after renal injury has transpired. There are no treatments to reverse or restore renal function once AKI has developed, other than supportive care. Early prediction of AKI enables proactive management and may improve patient outcomes. Objective: The primary aim was to develop a machine learning algorithm, NAVOY Acute Kidney Injury, capable of predicting the onset of AKI in ICU patients using data routinely collected in ICU electronic health records. The ultimate goal was to create a clinical decision support tool that empowers ICU clinicians to proactively manage AKI and, consequently, enhance patient outcomes. Methods: We developed the NAVOY Acute Kidney Injury algorithm using a hybrid ensemble model, which combines the strengths of both a Random Forest (Leo Breiman and Adele Cutler) and an XGBoost model (Tianqi Chen). To ensure the accuracy of predictions, the algorithm used 22 clinical variables for hourly predictions of AKI as defined by the Kidney Disease: Improving Global Outcomes guidelines. Data for algorithm development were sourced from the Massachusetts Institute of Technology Lab for Computational Physiology Medical Information Mart for Intensive Care IV clinical database, focusing on ICU patients aged 18 years or older. Results: The developed algorithm, NAVOY Acute Kidney Injury, uses 4 hours of input and can, with high accuracy, predict patients with a high risk of developing AKI 12 hours before onset. The prediction performance compares well with p

Background Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) may be considered for stabilization of patients with hemorrhage from below the diaphragm. Occluding the aorta is a powerful means of hemorrhagic control but is also associated with acute kidney injury, which increases mortality in trauma patients. Allowing for intermittent distal blood flow during REBOA application (iREBOA) could decrease this risk, but circulatory consequences have not been sufficiently elucidated. Therefore, we investigated circulatory effects and the renal artery blood flow (RBF) in iREBOA versus continuous, complete aortic occlusion (cREBOA). Methods In a porcine model of uncontrolled class III hemorrhage (34% estimated total blood volume, mean 1360 mL), swine (n = 12, mean weight 60.3 kg) were randomly assigned to iREBOA: 3-min full deflation every 10 min (n = 6), or cREBOA (n = 6), for 60 min of thoracic (zone I) application. The animals then underwent 60 min of reperfusion (critical care phase). Results Survival was 100% in iREBOA and 83% in cREBOA. The intermittent balloon deflation protocol was hemodynamically tolerable in 63% of reperfusion intervals. Systolic blood pressure decreased during the reperfusion intervals in iREBOA animals (mean 108 mm Hg versus 169 mm Hg; p < 0.005). No differences were detected in heart rate, cardiac output or stroke volume between methods. Troponin I increased in cREBOA after 60 min (mean 666-187 ng/L, p < 0.05). The norepinephrine requirement increased in cREBOA during reperfusion (mean infusion time 12.5-5.5 min; p < 0.05). Total ischemic time decreased in iREBOA (60.0-48.6 min; p < 0.001). RBF increased in iREBOA during balloon deflations and after 60 min reperfusion (61%-39% of baseline RBF; p < 0.05). Urine output increased in iREBOA (mean 135-17 mL; p < 0.001). Nephronal osteopontin, a marker of ischemic injury, increased in cREBOA (p < 0.05). Conclusion iREBOA was survivable, did not cause rebleeding, dec

Background: Acute kidney injury (AKI) represents a significant global health challenge, leading to increased patient distress and financial health care burdens. The development of AKI in intensive care unit (ICU) settings is linked to prolonged ICU stays, a heightened risk of long-term renal dysfunction, and elevated short-and long-term mortality rates. The current diagnostic approach for AKI is based on late indicators, such as elevated serum creatinine and decreased urine output, which can only detect AKI after renal injury has transpired. There are no treatments to reverse or restore renal function once AKI has developed, other than supportive care. Early prediction of AKI enables proactive management and may improve patient outcomes. Objective: The primary aim was to develop a machine learning algorithm, NAVOY Acute Kidney Injury, capable of predicting the onset of AKI in ICU patients using data routinely collected in ICU electronic health records. The ultimate goal was to create a clinical decision support tool that empowers ICU clinicians to proactively manage AKI and, consequently, enhance patient outcomes. Methods: We developed the NAVOY Acute Kidney Injury algorithm using a hybrid ensemble model, which combines the strengths of both a Random Forest (Leo Breiman and Adele Cutler) and an XGBoost model (Tianqi Chen). To ensure the accuracy of predictions, the algorithm used 22 clinical variables for hourly predictions of AKI as defined by the Kidney Disease: Improving Global Outcomes guidelines. Data for algorithm development were sourced from the Massachusetts Institute of Technology Lab for Computational Physiology Medical Information Mart for Intensive Care IV clinical database, focusing on ICU patients aged 18 years or older. Results: The developed algorithm, NAVOY Acute Kidney Injury, uses 4 hours of input and can, with high accuracy, predict patients with a high risk of developing AKI 12 hours before onset. The prediction performance compares well with p

Background: Acute kidney injury (AKI) represents a significant global health challenge, leading to increased patient distress and financial health care burdens. The development of AKI in intensive care unit (ICU) settings is linked to prolonged ICU stays, a heightened risk of long-term renal dysfunction, and elevated short-and long-term mortality rates. The current diagnostic approach for AKI is based on late indicators, such as elevated serum creatinine and decreased urine output, which can only detect AKI after renal injury has transpired. There are no treatments to reverse or restore renal function once AKI has developed, other than supportive care. Early prediction of AKI enables proactive management and may improve patient outcomes. Objective: The primary aim was to develop a machine learning algorithm, NAVOY Acute Kidney Injury, capable of predicting the onset of AKI in ICU patients using data routinely collected in ICU electronic health records. The ultimate goal was to create a clinical decision support tool that empowers ICU clinicians to proactively manage AKI and, consequently, enhance patient outcomes. Methods: We developed the NAVOY Acute Kidney Injury algorithm using a hybrid ensemble model, which combines the strengths of both a Random Forest (Leo Breiman and Adele Cutler) and an XGBoost model (Tianqi Chen). To ensure the accuracy of predictions, the algorithm used 22 clinical variables for hourly predictions of AKI as defined by the Kidney Disease: Improving Global Outcomes guidelines. Data for algorithm development were sourced from the Massachusetts Institute of Technology Lab for Computational Physiology Medical Information Mart for Intensive Care IV clinical database, focusing on ICU patients aged 18 years or older. Results: The developed algorithm, NAVOY Acute Kidney Injury, uses 4 hours of input and can, with high accuracy, predict patients with a high risk of developing AKI 12 hours before onset. The prediction performance compares well with p

Background: Acute kidney injury (AKI) represents a significant global health challenge, leading to increased patient distress and financial health care burdens. The development of AKI in intensive care unit (ICU) settings is linked to prolonged ICU stays, a heightened risk of long-term renal dysfunction, and elevated short-and long-term mortality rates. The current diagnostic approach for AKI is based on late indicators, such as elevated serum creatinine and decreased urine output, which can only detect AKI after renal injury has transpired. There are no treatments to reverse or restore renal function once AKI has developed, other than supportive care. Early prediction of AKI enables proactive management and may improve patient outcomes. Objective: The primary aim was to develop a machine learning algorithm, NAVOY Acute Kidney Injury, capable of predicting the onset of AKI in ICU patients using data routinely collected in ICU electronic health records. The ultimate goal was to create a clinical decision support tool that empowers ICU clinicians to proactively manage AKI and, consequently, enhance patient outcomes. Methods: We developed the NAVOY Acute Kidney Injury algorithm using a hybrid ensemble model, which combines the strengths of both a Random Forest (Leo Breiman and Adele Cutler) and an XGBoost model (Tianqi Chen). To ensure the accuracy of predictions, the algorithm used 22 clinical variables for hourly predictions of AKI as defined by the Kidney Disease: Improving Global Outcomes guidelines. Data for algorithm development were sourced from the Massachusetts Institute of Technology Lab for Computational Physiology Medical Information Mart for Intensive Care IV clinical database, focusing on ICU patients aged 18 years or older. Results: The developed algorithm, NAVOY Acute Kidney Injury, uses 4 hours of input and can, with high accuracy, predict patients with a high risk of developing AKI 12 hours before onset. The prediction performance compares well with p

Background Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) may be considered for stabilization of patients with hemorrhage from below the diaphragm. Occluding the aorta is a powerful means of hemorrhagic control but is also associated with acute kidney injury, which increases mortality in trauma patients. Allowing for intermittent distal blood flow during REBOA application (iREBOA) could decrease this risk, but circulatory consequences have not been sufficiently elucidated. Therefore, we investigated circulatory effects and the renal artery blood flow (RBF) in iREBOA versus continuous, complete aortic occlusion (cREBOA). Methods In a porcine model of uncontrolled class III hemorrhage (34% estimated total blood volume, mean 1360 mL), swine (n = 12, mean weight 60.3 kg) were randomly assigned to iREBOA: 3-min full deflation every 10 min (n = 6), or cREBOA (n = 6), for 60 min of thoracic (zone I) application. The animals then underwent 60 min of reperfusion (critical care phase). Results Survival was 100% in iREBOA and 83% in cREBOA. The intermittent balloon deflation protocol was hemodynamically tolerable in 63% of reperfusion intervals. Systolic blood pressure decreased during the reperfusion intervals in iREBOA animals (mean 108 mm Hg versus 169 mm Hg; p < 0.005). No differences were detected in heart rate, cardiac output or stroke volume between methods. Troponin I increased in cREBOA after 60 min (mean 666-187 ng/L, p < 0.05). The norepinephrine requirement increased in cREBOA during reperfusion (mean infusion time 12.5-5.5 min; p < 0.05). Total ischemic time decreased in iREBOA (60.0-48.6 min; p < 0.001). RBF increased in iREBOA during balloon deflations and after 60 min reperfusion (61%-39% of baseline RBF; p < 0.05). Urine output increased in iREBOA (mean 135-17 mL; p < 0.001). Nephronal osteopontin, a marker of ischemic injury, increased in cREBOA (p < 0.05). Conclusion iREBOA was survivable, did not cause rebleeding, dec