Beyond the Usual Suspects: Ethylene Glycol Poisoning Complicated by Rare Neurological Sequelae.

Ethylene glycol poisoning is a known clinical entity with established diagnostic and management protocols. However, instances presenting with rare neurological complications pose diagnostic challenges and necessitate prompt recognition and intervention. This report details the case of ethylene glycol poisoning in a 38-year-old male patient who initially presented with a history of brake oil consumption at his residence, followed by a delayed presentation with vomiting, abdominal pain, and reduced urine output, and subsequently developed unusual neurological sequelae, including unsteadiness, hearing difficulties, and an inability to close his eyes. Diagnostic assessment revealed cerebellar ataxia with bilateral sensory-neural hearing loss and facial nerve palsy. The patient was subsequently managed primarily for ethylene glycol poisoning, with conservative management for the neurological sequelae, and improved with no residual deficits. This case underscores the importance of promptly managing ethylene poisoning to prevent complications and sequelae as well as reduce morbidity for patients.

Determinants of acute kidney injury during high-power mechanical ventilation: secondary analysis from experimental data.

BACKGROUND: The individual components of mechanical ventilation may have distinct effects on kidney perfusion and on the risk of developing acute kidney injury; we aimed to explore ventilatory predictors of acute kidney failure and the hemodynamic changes consequent to experimental high-power mechanical ventilation. METHODS: Secondary analysis of two animal studies focused on the outcomes of different mechanical power settings, including 78 pigs mechanically ventilated with high mechanical power for 48 h. The animals were categorized in four groups in accordance with the RIFLE criteria for acute kidney injury (AKI), using the end-experimental creatinine: (1) NO AKI: no increase in creatinine; (2) RIFLE 1-Risk: increase of creatinine of > 50%; (3) RIFLE 2-Injury: two-fold increase of creatinine; (4) RIFLE 3-Failure: three-fold increase of creatinine; RESULTS: The main ventilatory parameter associated with AKI was the positive end-expiratory pressure (PEEP) component of mechanical power. At 30 min from the initiation of high mechanical power ventilation, the heart rate and the pulmonary artery pressure progressively increased from group NO AKI to group RIFLE 3. At 48 h, the hemodynamic variables associated with AKI were the heart rate, cardiac output, mean perfusion pressure (the difference between mean arterial and central venous pressures) and central venous pressure. Linear regression and receiving operator characteristic analyses showed that PEEP-induced changes in mean perfusion pressure (mainly due to an increase in CVP) had the strongest association with AKI. CONCLUSIONS: In an experimental setting of ventilation with high mechanical power, higher PEEP had the strongest association with AKI. The most likely physiological determinant of AKI was an increase of pleural pressure and CVP with reduced mean perfusion pressure. These changes resulted from PEEP per se and from increase in fluid administration to compensate for hemodynamic impairment consequent to high PEEP.

Assessing Discharge Communication and Follow-up of Acute Kidney Injury in British Columbia: A Retrospective Chart Review.

Background and objective: Acute kidney injury (AKI) affects up to 20% of hospitalizations and is associated with chronic kidney disease, cardiovascular disease, increased mortality, and increased health care costs. Proper documentation of AKI in discharge summaries is critical for optimal monitoring and treatment of these patients once discharged. Currently, there is limited literature evaluating the quality of discharge communication after AKI. This study aimed to evaluate the accuracy and quality of documentation of episodes of AKI at a tertiary care center in British Columbia, Canada. Methods design setting patients and measurements: This was a retrospective chart review study of adult patients who experienced AKI during hospital admission between January 1, 2018, and December 31, 2018. Laboratory data were used to identify all admissions to the cardiac and general medicine ward complicated by AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. A random sample of 300 AKI admissions stratified by AKI severity (eg, stages 1, 2, and 3) were identified for chart review. Patients were excluded if they required ongoing renal replacement therapy after admission, had a history of kidney transplant, died during their admission, or did not have a discharge summary available. Discharge summaries were reviewed for documentation of the following: presence of AKI, severity of AKI, AKI status at discharge, practitioner and laboratory follow-up plans, and medication changes. Results: A total of 1076 patients with 1237 AKI admissions were identified. Of the 300 patients selected for discharge summary review, 38 met exclusion criteria. In addition, AKI was documented in 140 (53%) discharge summaries and was more likely to be documented in more severe AKI: stage 1, 38%; stage 2, 51%; and stage 3, 75%. Of those with their AKI documented, 94 (67%) documented AKI severity, and 116 (83%) mentioned the AKI status or trajectory at the time of discharge. A total of 239 (91%) of discharge summaries mentioned a follow-up plan with a practitioner, but only 23 (10%) had documented follow-up with nephrology. Patients with their AKI documented were more likely to have nephrology follow-up than those without AKI documented (17% vs 1%). Regarding laboratory investigations, 92 (35%) of the summaries had documented recommendations. In summaries that included medications typically held during AKI, only about half made specific reference to those medications being held, adjusted, or documented a post-discharge plan for that medication. For those with nonsteroidal anti-inflammatory drugs (NSAIDs) listing, 64% of discharge summaries mentioned holding, and 9% mentioned a discharge plan. For those with angiotensin converting enzyme inhibitor (ACEi)/angiotensin II receptor blocker (ARB) listing, 38% mentioned holding these medications, and 46% mentioned a discharge plan. In summaries with diuretics listed, 35% mentioned holding, and 51% included a discharge plan. Conclusions and limitations: We found suboptimal quality and completeness of discharge reporting in patients hospitalized with AKI. This may contribute to inadequate follow-up and post-hospitalization care for this patient population. Strategies are required for increasing the presence and quality of AKI reporting in discharge summaries. Limitations include our definition of AKI based on lab criteria, which may have missed some of the injuries that met the criteria based on urine output. Another limitation is that our definition of AKI based on the highest and lowest creatinine during admission may have led to some overclassification. In addition, without outpatient laboratories, it is possible that we have not captured the true baseline creatinine in some patients.

Contexte et objectif: L'insuffisance rénale aiguë (IRA) complique jusqu'à 20 % des hospitalisations; elle est associée à l'insuffisance rénale chronique, aux maladies cardiovasculaires, à une mortalité accrue et à une augmentation des coûts de santé. La documentation appropriée de l'IRA dans les résumés de départ est essentielle pour optimiser la surveillance et le traitement des patients après leur sortie de l'hôpital. Il existe peu de littérature évaluant la qualité de la documentation de l'IRA dans les résumés de départ. Cette étude visait à évaluer l'exactitude et la qualité de la documentation des épisodes d'IRA dans un center de soins tertiaires de la Colombie-Britannique (Canada). Méthodologie conception et cadre de l'étude sujets et mesures: Il s'agit d'une étude rétrospective des dossiers de patients adultes ayant présenté une IRA au cours de leur admission à l'hôpital entre le 1er janvier 2018 et le 31 décembre 2018. Les données de laboratoire ont été utilisées pour répertorier toutes les admissions compliquées par une IRA (définie par les critères KDIGO) dans les services de cardiologie et de médecine générale. Un échantillon aléatoire de 300 admissions avec IRA stratifiée selon sa gravité (p. ex., stade, 1, 2 et 3) a été constitué pour l'examen des dossiers. Ont été exclus les patients qui avaient eu besoin d'une thérapie de suppléance rénale continue après leur admission, ceux qui avaient des antécédents de transplantation rénale, ceux qui étaient décédés pendant leur admission et ceux pour qui aucun résumé de départ n'était disponible. Les résumés de départ ont été examinés à la recherche d'une mention des éléments suivants : présence d'une IRA, gravité de l'IRA, statut de l'IRA à la sortie, plans de suivi pour les tests de laboratoire et suivi avec un praticien, changements dans la médication. Résultats: En tout, 1 076 patients avec un total de 1 237 admissions avec IRA ont été identifiés. Parmi les 300 patients sélectionnés pour l'examen du résumé de départ, 38 répondaient aux critères d'exclusion. L'IRA avait été documentée dans 140 (53 %) des cas et plus elle était grave, plus elle était susceptible d'être documentée (stade 1 = 38 %; stade 2 = 51 %; stade 3 = 75 %). Parmi ceux où l'IRA était documentée, 94 (67 %) mentionnaient sa gravité et 116 (83 %) mentionnaient son statut ou sa trajectoire à la sortie du patient. Un plan de suivi avec le praticien était mentionné dans 239 (91 %) des résumés de départ, mais seuls 23 (10 %) mentionnaient un suivi en néphrologie. Les patients dont l'IRA était documentée étaient plus susceptibles de faire l'objet d'un suivi en néphrologie que ceux sans mention de l'IRA (17 % contre 1 %). En ce qui concerne les plans de suivi de laboratoire, 92 (35 %) des résumés contenaient des recommandations. Dans les résumés qui mentionnaient des médicaments normalement maintenus pendant un épisode d'IRA, seule la moitié environ faisait spécifiquement référence à ces médicaments comme ayant été cessés, ajustés ou documentés dans un plan post-sortie. Dans les résumés de départ qui listaient des AINS, 64 % mentionnaient qu'ils avaient été cessés temporairement et 9 % comprenaient un plan au congé de l'hôpital. Dans les résumés de départ qui listaient des IECA/ARA, 38 % mentionnaient que ces médicaments avaient été cessés temporairement et 46 % comprenaient un plan au congé de l'hôpital. Dans les résumés qui listaient des diurétiques, 35 % mentionnaient qu'ils avaient été cessés temporairement et 51 % comprenaient un plan au congé de l'hôpital. Limites et conclusion: Nous avons constaté que la qualité et l'exhaustivité des résumés de départ étaient sous-optimales chez les patients hospitalisés ayant vécu un épisode d'IRA. Cette situation peut contribuer à l'inadéquation du suivi et des soins post-hospitalization pour cette population de patients. Des stratégies sont nécessaires pour accroître la documentation d'un épisode d'IRA dans les résumés de départ et augmenter la qualité de sa communication. Les résultats de cette étude sont notamment limités par notre définition de l'IRA fondée sur des critères de laboratoire qui pourraient avoir manqué des patients répondant aux critères fondés sur la production d'urine. Notre définition de l'IRA fondée sur le taux de créatinine le plus élevée et le plus faible pendant l'admission pourrait également avoir conduit à un surdiagnostic. En outre, sans les résultats de laboratoires externes, il est possible que nous n'ayons pas saisi la mesure initiale réelle de la créatinine chez certains patients.

Avacopan as an additional therapeutic intervention to promote renal recovery in severe ANCA-associated vasculitis: A case report.

Avacopan, a C5a receptor antagonist (C5aR) presents a new therapeutic option to improve outcomes in ANCA-associated vasculitis (AAV). Here we present a case report of a patient initially requiring kidney replacement therapy (KRT), where avacopan was added as an additional adjunctive therapeutic agent late in the treatment course.

Nutrition in critically ill children with acute kidney injury on continuous kidney replacement therapy: a 2023 executive summary.

OBJECTIVES: Nutrition plays a vital role in the outcome of critical illness in children, particularly those with acute kidney injury. Currently, there are no established guidelines for children with acute kidney injury treated with continuous kidney replacement therapy. Our objective was to create clinical practice points for nutritional assessment and management in critically ill children with acute kidney injury receiving continuous kidney replacement therapy. METHODS: An electronic search using PubMed and an inclusive academic library search (including MEDLINE, Cochrane, and Embase databases) was conducted to find relevant English-language articles on nutrition therapy for children (<18 y of age) receiving continuous kidney replacement therapy. RESULTS: The existing literature was reviewed by our work group, comprising pediatric nephrologists and experts in nutrition. The modified Delphi method was then used to develop a total of 45 clinical practice points. The best methods for nutritional assessment are discussed. Indirect calorimetry is the most reliable method of predicting resting energy expenditure in children on continuous kidney replacement therapy. Schofield equations can be used when indirect calorimetry is not available. The non-intentional calories contributed by continuous kidney replacement therapy should also be accounted for during caloric dosing. Protein supplementation should be increased to account for the proteins, peptides, and amino acids lost with continuous kidney replacement therapy. CONCLUSIONS: Clinical practice points are provided on nutrition assessment, determining energy needs, and nutrient intake in children with acute kidney injury and on continuous kidney replacement therapy based on the existing literature and expert opinions of a multidisciplinary panel.

Anticoagulation practices for continuous renal replacement therapy: a survey of physicians from the United States.

BACKGROUND: During continuous renal replacement therapy (CRRT), anticoagulants are recommended for patients at low risk of bleeding and not already receiving systemic anticoagulants. Current anticoagulants used in CRRT in the US are systemic heparins or regional citrate. To better understand use of anticoagulants for CRRT in the US, we surveyed nephrologists and critical care medicine (CCM) specialists. METHODS: The survey contained 30 questions. Respondents were board certified and worked in intensive care units of academic medical centers or community hospitals. RESULTS: 150 physicians (70 nephrologists and 80 CCM) completed the survey. Mean number of CRRT machines in use increased ∼30% from the pre-pandemic era to 2022. Unfractionated heparin was the most used anticoagulant (43% of estimated patients) followed by citrate (28%). Respondents reported 29% of patients received no anticoagulant. Risk of hypocalcemia (52%) and citrate safety (42%) were the predominant reasons given for using no anticoagulant instead of citrate in heparin-intolerant patients. 84% said filter clogging was a problem when no anticoagulant was used, and almost 25% said increased transfusions were necessary. Respondents using heparin (n = 131) considered it inexpensive and easily obtainable, although of moderate safety, citing concerns of heparin-induced thrombocytopenia and bleeding. Anticoagulant citrate dextrose solution was the most used citrate. Respondents estimated that 37% of patients receiving citrate develop hypocalcemia and 17% citrate lock. CONCLUSIONS: Given the increased use of CRRT and the lack of approved, safe, and effective anticoagulant choices for CRRT in the US, effective use of current and other anticoagulant options needs to be evaluated.

Acute kidney injury associated with piperacillin-tazobactam versus other antibiotics combined with vancomycin in critically ill patients: A retrospective cohort study.

Introduction: Evidence of acute kidney injury (AKI) induced by piperacillin-tazobactam (Piptazo) versus other broad-spectrum antibiotics (BSA) combined with vancomycin has been established in the literature. However, there is limited evidence regarding these combinations among critically ill patients. This study assessed the risk of nephrotoxicity of Piptazo versus other BSA as an add-on to vancomycin among patients admitted to an intensive care unit (ICU). Methods: We have reviewed patients' charts retrospectively to investigate AKI incidence among ICU patients receiving Piptazo versus other BSA as an add-on to vancomycin. Furthermore, we have assessed the duration of AKI and ICU stay, as well as the association between patients' criteria and risk of AKI using logistic regression analyses. Results: A total of 79 patients were included, 50 patients received the Piptazo combination while 29 patients received other BSA combinations. Almost 52 % of the patients in the Piptazo group developed AKI while only 37.9 % of those in the BSA group did, yet the difference was not statistically significant (p = 0.22). On the other hand, the risk of AKI was highly associated with vancomycin trough concentration above 20 mcg/mL, nephrotoxic medications, and African descent (OR 7.1, 95 %CI 1.96-25.84, OR 3.94, 95 %CI 1.27-12.2, OR 3.53, 95 %CI 1.1-11.27, respectively). Conclusion: Although the difference in AKI risk was not statistically significant between Piptazo versus BSA groups, the elevated trough concentration of vancomycin and the concomitant use of nephrotoxic medications, were found to increase the risk of AKI, independently of the combined antibiotics used.

Renal safety and survival among acutely ill hospitalized patients treated by blockers of the Renin-Angiotensin axis or loop diuretics: a single-center retrospective analysis.

BACKGROUND: Concern exists regarding the renal safety of blocking the renin-angiotensin system (RAS) during acute illness, especially in the presence of volume depletion and hemodynamic instability. METHODS: We explored the impact of loop diuretics and RAS blockers on the likelihood of developing acute kidney injury (AKI) or acute kidney functional recovery (AKR) among inpatients. Adjusted odds ratio for AKI, AKR and mortality was calculated, using logistic regression models, with subgroup analysis for patients with estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2, corrected for blood pressure measurements. RESULTS: 53,289 patients were included. RAS blockade was associated with reduced adjusted odds ratio for both AKI (0.76, CI 0.70-0.83) AKR (0.55, 0.52-0.58), and mortality within 30 days (0.44, 0.41-0.48), whereas loop diuretics were associated with increased risk of AKI (3.75, 3.42-4.12) and mortality (1.71, 1.58-1.85) and reduced AKR (0.71, 0.66-0.75). Comparable impact of RAS blockers and loop diuretics on renal outcomes and death was found among 6,069 patients with eGFR < 30 ml/min/1.73m2. RAS inhibition and diuretics tended to increase the adjusted odds ratios for AKI and to reduce the likelihood of AKR in hypotensive patients. CONCLUSIONS: Reduced blood pressure, RAS blockers and diuretics affect the odds of developing AKI or AKR among inpatients, suggesting possible disruption in renal functional reserve (RFR). As long as blood pressure is maintained, RAS inhibition seems to be safe and renoprotective in this population, irrespective of kidney function upon admission, and is associated with reduced mortality.

Enfermedad renal crónica agudizada como causa de mortalidad en paciente con COVID-19

Introducción: La infección por SARS-CoV-2 en pacientes con enfermedad renal crónica se asocia a larga estadía hospitalaria, aparición de complicaciones y mortalidad. Objetivo: Describir el caso clínico de un paciente con enfermedad renal crónica agudizada como causa de mortalidad en presencia de la infección por la COVID-19. Presentación del caso: Paciente masculino de 69 años con antecedentes de enfermedad renal crónica estadio 3a que ingresó a la institución hospitalaria con diagnóstico de COVID-19 y que durante su estadía presentó cifras elevadas de creatinina sérica con el consiguiente desarrollo de injuria renal aguda. Después de cinco sesiones de hemodiálisis mejoró el estado general del paciente y las cifras de creatinina disminuyeron parcialmente. A pesar de la mejoría clínica, el paciente progresó hacia el último estadio de la enfermedad renal crónica. Luego de tres semanas bajo terapia hemodialítica crónica falleció a causa de síndrome coronario agudo con elevación del segmento ST. Conclusiones: El pronóstico de los pacientes con daño renal que desarrollan la COVID-19 es desfavorable. La infección por SARS-CoV-2 favorece la progresión hacia los estadios finales de la enfermedad renal crónica con riesgo incrementado de la mortalidad.

Introduction: SARS-CoV-2 infection in patients with chronic kidney disease is associated with a long hospital stay, the appearance of complications and mortality. Objective: To describe the clinical case of a patient with exacerbated chronic kidney disease as a cause of mortality in the presence of COVID-19 infection. Clinical case: A 69-year-old male patient with a history of stage 3a chronic kidney disease who was admitted to a hospital with a diagnosis of COVID-19 and who during his stay presented elevated serum creatinine levels with the subsequent development of acute kidney injury. After five hemodialysis sessions, the patient's general condition improved and the creatinine levels partially decreased. Despite clinical improvement, the patient progressed to the last stage of chronic kidney disease. After three weeks under chronic hemodialytic therapy, the patient died due to ST-segment elevation acute coronary syndrome. Conclusions: The prognosis of patients with kidney damage who develop COVID-19 is unfavorable. SARS-CoV-2 infection favors progression to the final stages of chronic kidney disease with an increased risk of mortality.

Association between triglyceride-glucose index and AKI in ICU patients based on MIMICIV database: a cross-sectional study.

BACKGROUND: Methods for early prediction of the occurrence of acute kidney injury (AKI) were limited. The relationship between triglyceride glucose index (TyG) and the incidence of acute kidney injury in ICU patients is unclear. This study aims to explore the relationship between the two. METHODS: Based on their TyG index, participants from the Intensive Care Medical Information Market IV (MIMIC-IV) were divided into quartiles. A logistic regression model was constructed based on the risk of acute kidney injury as the main outcome, in order to detect a potential relationship that may exist between the TyG index and acute kidney injury in ICU patients. Finally, in order to confirm the relationship existing between the TyG index and the results, a restricted cubic spline model was used. RESULTS: In total, 54,263 patients were involved in our present study, of whom 48.2% were male. The occurrence of acute kidney injury was 25.1%. An independent relationship was observed between the TyG index and an increased risk of acute kidney injury through multivariate logistic regression analysis (OR, 1.28 [95% CI 1.22-1.35] p < 0.001). Q4 (5.344-9.911) of the TyG index quartiles was independently associated with an increase in the risk of acute kidney injury (OR, 1.43 [95% CI (1.32-1.54)] p < 0.001). Through the restricted cubic spline regression model, the risk of acute kidney injury was also demonstrated to increase linearly with an increase in the TyG index. CONCLUSION: The triglyceride glucose index is related to the risk of acute kidney injury in ICU patients. In the future, in order to further validate this finding, larger prospective studies are needed.

A fair exchange: why living kidney donors in England should be financially compensated.

Every year, hundreds of patients in England die whilst waiting for a kidney transplant, and this is evidence that the current system of altruistic-based donation is not sufficient to address the shortage of kidneys available for transplant. To address this problem, we propose a monopsony system whereby kidney donors can opt-in to receive financial compensation, whilst still preserving the right of individuals to donate without receiving any compensation. A monopsony system describes a market structure where there is only one 'buyer'-in this case the National Health Service. By doing so, several hundred lives could be saved each year in England, wait times for a kidney transplant could be significantly reduced, and it would lessen the burden on dialysis services. Furthermore, compensation would help alleviate the common disincentives to living kidney donation, such as its potential associated health and psychological costs, and it would also help to increase awareness of living kidney donation. The proposed system would also result in significant cost savings that could then be redirected towards preventing kidney disease and reducing health disparities. While concerns about exploitation, coercion, and the 'crowding out' of altruistic donors exist, we believe that careful implementation can mitigate these issues. Therefore, we recommend piloting financial compensation for living kidney donors at a transplant centre in England.

Evaluation of Cisplatin-Induced Acute Renal Failure Amelioration Using Fondaparinux and Alteplase.

Acute renal failure (ARF) is a deleterious condition with increased mortality or healthcare costs or dialysis-dependent end-stage renal disease. The study aims to compare prophylaxis with fondaparinux (Fund) vs. treatment with alteplase (Alt) in ameliorating cisplatin (Cis)-induced ARF. Sixty male mice were equally divided randomly into six groups of control, Cis, Alt, and Cis + Alt groups receiving normal saline for 10 days. All four groups except for the control received Cis (30 mg/kg, i.p.) on day 7, and 6 h later, both the Alt groups received Alt (0.9 mg/kg, i.v.). The animal groups Fund and Fund + Cis received Fund (5 mg/kg, i.p.) for 10 days, and the Fund + Cis group on day 7 received Cis. All the animal groups were euthanized 72 h after the Cis dose. The Fund + Cis group showed significantly increased expression levels of platelet count, retinoid X receptor alpha (RXR-α) and phosphorylated Akt (p-Akt) in addition to decreased levels of urea, blood urea nitrogen (BUN), uric acid, white blood cells (WBCs), red blood cells (RBCs), relative kidney body weight, kidney injury score, glucose, prothrombin (PT), A Disintegrin And Metalloproteinases-10 (ADAM10), extracellular matrix deposition, protease-activated receptor 2 (PAR-2), and fibrinogen expression when compared to the Cis-only group. Meanwhile, the Cis + Alt group showed increased caspase-3 expression in addition to decreased levels of urea, BUN, uric acid, WBCs, RBCs, glucose, platelet count and PT expression with a marked decrease in PAR-2 protein expression compared to the Cis group. The creatinine levels for both the Fund + Cis and Cis + Alt groups were found to be comparable to those of the Cis-only group. The results demonstrate that the coagulation system's activation through the stimulation of PAR-2 and fibrinogen due to Cis-induced ADAM10 protein expression mediated the apoptotic pathway, as indicated by caspase-3 expression through the p-Akt pathway. This is normally accompanied by the loss of RXR-α distal and proximal tubules as lipid droplets. When the animals were pre-treated with the anticoagulant, Fund, the previous deleterious effect was halted while the fibrinolytic agent, Alt, most of the time failed to treat Cis-induced toxicity.

Inhibition of pyruvate dehydrogenase kinase 4 ameliorates kidney ischemia-reperfusion injury by reducing succinate accumulation during ischemia and preserving mitochondrial function during reperfusion.

Ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury (AKI), is still without effective therapies. Succinate accumulation during ischemia followed by its oxidation during reperfusion leads to excessive reactive oxygen species (ROS) and severe kidney damage. Consequently, the targeting of succinate accumulation may represent a rational approach to the prevention of IR-induced kidney injury. Since ROS are generated primarily in mitochondria, which are abundant in the proximal tubule of the kidney, we explored the role of pyruvate dehydrogenase kinase 4 (PDK4), a mitochondrial enzyme, in IR-induced kidney injury using proximal tubule cell-specific Pdk4 knockout (Pdk4ptKO) mice. Knockout or pharmacological inhibition of PDK4 ameliorated IR-induced kidney damage. Succinate accumulation during ischemia, which is responsible for mitochondrial ROS production during reperfusion, was reduced by PDK4 inhibition. PDK4 deficiency established conditions prior to ischemia resulting in less succinate accumulation, possibly because of a reduction in electron flow reversal in complex II, which provides electrons for the reduction of fumarate to succinate by succinate dehydrogenase during ischemia. The administration of dimethyl succinate, a cell-permeable form of succinate, attenuated the beneficial effects of PDK4 deficiency, suggesting that the kidney-protective effect is succinate-dependent. Finally, genetic or pharmacological inhibition of PDK4 prevented IR-induced mitochondrial damage in mice and normalized mitochondrial function in an in vitro model of IR injury. Thus, inhibition of PDK4 represents a novel means of preventing IR-induced kidney injury, and involves the inhibition of ROS-induced kidney toxicity through reduction in succinate accumulation and mitochondrial dysfunction.

Non-ST Segment Elevation Myocardial Infarction (NSTEMI) in the Setting of Severe Rhabdomyolysis and COVID-19 Infection: A Case Report.

We present a case report of a non-ST segment elevation myocardial infarction (NSTEMI) occurring in an 89-year-old male with severe rhabdomyolysis and COVID-19 infection. The patient had a complex medical history, including non-ischemic cardiomyopathy, sinus bradycardia status post permanent pacemaker placement, and multiple comorbidities. He presented to the emergency department after a mechanical fall and was found to be COVID-19 positive. Despite the absence of typical symptoms, the patient's elevated troponin levels and electrocardiogram findings indicated NSTEMI. The initial management included an acute coronary syndrome protocol and admission to the cardiac intensive care unit. During the hospitalization, the patient developed acute hypoxic respiratory failure and was treated for COVID-19 pneumonia. The patient's renal function and creatine kinase levels showed improvement, and cardiac catheterization revealed non-obstructive coronaries. The patient was discharged in stable condition with a follow-up scheduled.

Pulmonary Angiosarcoma With Synchronous Invasive Aspergillosis Presenting as Diffuse Alveolar Hemorrhage and Acute Kidney Injury: A Case Report of a Previously Unreported Combination Posing a Diagnostic Challenge.

Angiosarcoma is a rare soft tissue sarcoma originating from endothelial cells. It can occur anywhere when there is a blood vessel or lymphatic channel, making highly perfused cutaneous sites their usual location, though they can also develop within visceral structures. Pulmonary angiosarcoma is usually caused by metastasis from other primary sites. The clinical course of pulmonary angiosarcoma is very aggressive, and the prognosis is poor. We present a case of a 55-year-old man who presented to the hospital with progressive exertional dyspnea and right-sided pleuritic chest pain for the past few days. He was found to have recurrent anemia and acute kidney injury. His hospital course was complicated by the development of hypoxia and hemoptysis. Computed tomography of the chest without contrast revealed bilateral nodular, ground-glass opacities compatible with diffuse alveolar hemorrhage. Further investigation with a lung biopsy revealed epithelioid angiosarcoma with extensive microvascular tumor emboli and invasive pulmonary aspergillosis (Aspergillus fumigatus) with patchy necrotizing pneumonia. He later developed acute hypoxic respiratory failure and worsening kidney failure, so he was transferred to the intensive care unit. Upon discussing with the family, the patient was put on comfort measures, and he passed away the following day. We present a rare presentation of concurrence of pulmonary angiosarcoma and invasive aspergillosis. Upon searching the literature, our case is one of the first to report such concurrence. Because of its rarity, the non-specific clinical presentation makes the diagnosis challenging.

Acute Cocaine Intoxication: An Approach to Severe Hepatic and Renal Dysfunctions.

Cocaine is a highly addictive substance. Its poisoning can lead to potentially fatal multi-organ dysfunction. We report a case of cocaine overdose with severe multi-organ dysfunction. A healthy 51-year-old man was admitted to the emergency room due to behaviour changes and seizure after inhaling crack. Multiple dysfunctions were developed, with emphasis on liver and kidney dysfunction, due to their severity. The patient had marked hepatic cytolysis with a peak on the third day with alanine aminotransferase (ALT) and aspartate aminotransferase (AST): 7941 and 4453 IU/L, respectively with mild coagulopathy and hyperbilirubinemia. Underwent empirical treatment with acetylcysteine ​​with good clinical response. Also developed anuric AKIN3 acute kidney injury secondary to rhabdomyolysis, requiring treatment with intermittent haemodialysis. The approach to a case with severe multiorgan dysfunction is described, with special emphasis on the use of acetylcysteine. The good evolution of the patient can corroborate the use of this drug as a potential modifier of prognosis.

Serum Insulin-Like Growth Factor-Binding Protein 7 Deriving from Spleen and Lung Could Be Used for Early Recognition of Cardiac Surgery-Associated Acute Kidney Injury.

INTRODUCTION: The utility of arithmetic product of urinary tissue metalloproteinase inhibitor 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7) concentrations has been widely accepted on early diagnosis of acute kidney injury (AKI). However, which organ is the main source of those two factors and how the concentration of IGFBP7 and TIMP2 changed in serum during AKI still remain to be defined. METHODS: In mice, gene transcription and protein levels of IGFBP7/TIMP2 in the heart, liver, spleen, lung, and kidney were measured in both ischemia-reperfusion injury (IRI)- and cisplatin-induced AKI models. Serum IGFBP7 and TIMP2 levels were measured and compared in patients before cardiac surgery and at inclusion (0 h), 2 h, 6 h, and 12 h after intensive care unit (ICU) admission, and compared with serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and serum uric acid (UA). RESULTS: In mouse IRI-AKI model, compared with the sham group, the expression levels of IGFBP7 and TIMP2 did not change in the kidney, but significantly upregulated in the spleen and lung. Compared with patients who did not develop AKI, the concentration of serum IGFBP7 at as early as 2 h after ICU admission (sIGFBP7-2 h) was significantly higher in patients who developed AKI. The relationships between sIGFBP7-2 h in AKI patients and log2 (SCr), log2 (BUN), log2 (eGFR), and log2 (UA) were statistically significant. The diagnostic performance of sIGFBP7-2 h measured by the macro-averaged area under the receiver operating characteristic curve was 0.948 (95% CI, 0.853-1.000; p < 0.001). CONCLUSION: The spleen and lung might be the main source of serum IGFBP7 and TIMP2 during AKI. The serum IGFBP7 value demonstrated good predictive accuracy for AKI following cardiac surgery within 2 h after ICU admission.

Animal models of kidney iron overload and ferroptosis: a review of the literature.

In recent years, it has been identified that excess iron contributes to the development of various pathologies and their complications. Kidney diseases do not escape the toxic effects of iron, and ferroptosis is identified as a pathophysiological mechanism that could be a therapeutic target to avoid damage or progression of kidney disease. Ferroptosis is cell death associated with iron-dependent oxidative stress. To study the effects of iron overload (IOL) in the kidney, numerous animal models have been developed. The methodological differences between these models should reflect the IOL-generating mechanisms associated with human IOL diseases. A careful choice of animal model should be considered for translational purposes.

From Toxic Ingestion to Cancer: Dramatic Acidosis as a Myeloma-Defining Event.

Acute kidney failure has myriad causes and presentations. This is a case of an individual with a history of alcohol abuse and a previous suicide attempt presenting with acute kidney failure and altered mentation accompanied by an anion gap metabolic acidosis with an elevated osmolar gap. These findings were concerning for toxic alcohol ingestion, but the patient was ultimately diagnosed with multiple myeloma. This case demonstrates the multiple factors that can impact both the anion and osmolar gaps. It shows that the traditionally held dogma about the meaning of anion or osmolar gaps may cloud an otherwise more obscure etiology. It illustrates a dramatic presentation of acute myeloma, for which early recognition is essential to initiate appropriate chemotherapy for a chance at preservation of renal function.

Factors Predictive of Development of Acute Kidney Injury in Patients With COVID-19 in Brunei Darussalam.

INTRODUCTION: Acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients affects their health outcomes. Incidence and outcomes varied in the literature, particularly with different population and epidemiological demographics. Data remain scarce in the Southeast Asia region. We report the incidence, outcomes, pattern, types of AKI, and factors that influence AKI patient outcomes in Brunei Darussalam. METHODS: All patients (N = 930) with COVID-19 who were admitted to the National Isolation Center (between 7th August 2021 and 30thSeptember 2021) were included in the study. The confirmation of AKI was based on the KDIGO (Kidney Disease Improving Global Outcomes) criteria. RESULTS: The mean age of the patients was 41.9 ± 14.4 years with diabetes mellitus (DM), hypertension (HT), and chronic kidney disease (CKD) accounting for 11.7%, 29.1%, and 4.8% of comorbidities, respectively. Overall, 109 (11.7%) had AKI (KDIGO Stage 1 [67.9%], 2 [13.8%], and 3 [18.3%]), while 75.2% of the cases occurred pre-admission and 26.6% were cases of acute exacerbation of CKD. Univariate analysis identified age (odd ratio [OR] 1.06), male gender (OR 1.63), local nationality (OR 8.03), DM (OR 4.44), HT (OR 5.29), vascular disease (OR 6.08), presence of gastrointestinal symptoms (OR 2.08), antibiotic (OR 3.70) and nephrotoxins exposures (OR 8.57) as significant variables. Multivariate analysis showed age (adjusted OR [AOR] 1.04), male gender (AOR 1.67), gastrointestinal symptoms (AOR 1.61), antibiotic (AOR 2.34), and nephrotoxins exposure (AOR 4.73) as significant. CONCLUSIONS: Our study showed that one in nine patients with COVID-19 developed AKI with almost a third having stages 2 and 3 AKI. Older age, male gender, presence of GI symptoms, and antibiotic and nephrotoxin exposures were significant predictors of AKI. Patients with these factors should be prioritized for admission and treatment. Even though manifestations are generally now less severe, findings from this study can guide the management of COVID-19 as the disease enters the endemic stage. Furthermore, lessons learned from the COVID-19 pandemic will provide useful information and knowledge for future viral outbreaks or pandemics.