Acute Failure Research Articles

COLONOSCOPY-RELATED NEPHROPATHY

Colonoscopy is a widely used tool for the diagnosis and treatment of colon disease [1]. It is the gold standart to visualize the large bowel [2]. Acute phosphate nephropathy (APhN) is a clinical entity which causes acute and subsequent chronic renal failure after exposure to oral sodium phosphate (OSP) bowel purgatives. APhN is seen as a result of oral sodium phosphate use in patients undergoing bowel cleansing before colonoscopy [3]. Generally, patients who will undergo colonoscopy are given 45 ml of OSP twice, starting 12-24 hours before the procedure. After intestinal absorption, elevated urea and creatinine, transient hyperphosphatemia, hypocalcemia, hypernatremia, hyponatremia, hypokalemia and high anion gap metabolic acidosis may also be observed [4]. Advanced age, ACEi/ARB use, acute or chronic kidney disese or the presence of a kidney transplant, retention of OSP resulting from poor bowel motility or colitis, female gender, volume depletion, hypertension, diabetes, and diuretic, lithium, or nonsteroidal anti-inflammatory drug use are considered as risk factors [5]. This case report describes a patient who developed nephropathy and required urgent observation and treatment after phosphate administration before colonoscopy.

Mechanical circulatory support reduces renal sympathetic nerve activity in an ovine model of acute myocardial infarction.

The use of circulatory assist devices has been shown to improve glomerular filtration rate and reduce the incidence of acute kidney injury in patients following acute cardiac pathology. However, the mechanisms of improvement in kidney function are not clear. We tested the hypothesis that mechanical circulatory support would result in a decrease in directly recorded renal sympathetic nerve activity (RSNA) and mediate the improvement in renal blood flow (RBF) in a setting of acute myocardial infarction (AMI)-induced left ventricular systolic dysfunction. An anaesthetized ovine model was used to induce AMI (n = 8) using injections of microspheres into the left coronary artery in one group. The second group did not undergo embolization (n = 6). The effects of mechanical circulatory support using the Impella CP on directly recorded renal sympathetic nerve activity were examined in these two groups of animals. Injection of microspheres resulted in a drop in mean arterial pressure (MAP) of 21 ± 4mmHg compared to baseline values (p < 0.05; n = 8). This was associated with a 67% increase in renal sympathetic nerve activity (RSNA; from 16 ± 5 to 21 ± 5 spikes/s; p < 0.05; n = 7). Impella CP support significantly increased MAP by 13 ± 1.5mmHg at pump level 8 (p < 0.05) in the AMI group. Incremental pump support resulted in a significant decrease in RSNA (p < 0.05) in both groups. At pump level P8in the AMI group, RSNA was decreased by 21 ± 5.5% compared to pump level P0 when the pump was not on. Our data indicate that the improvement in kidney function following mechanical circulatory support may be mediated in part by renal sympathoinhibition.

Benefit of Expedited Time to Hip Fracture Surgery Differs Based on Patient Risk Profile.

To identify which hip fracture patients benefit the most from operative repair within 24 hours of Emergency Department (ED) presentation based on patient risk stratification. Design: Retrospective Cohort. Academic Medical Center. Patients operatively treated for an AO/OTA 31A, 31B, or 32A hip fracture. Each patient was placed into an "individualized risk quartile" (IRQ) using a validated risk stratification tool (The Score for Trauma Triage in the Geriatric and Middle-Aged [STTGMA], a tool proven to predict inpatient mortality in trauma patients). Patients were risk stratified into minimal-, low-, moderate-, and high-risk IRQ's. In each cohort, patients were separated into three groups based on their time from ED arrival to surgery (< 24 hours, > 24 hours and < 48 hours, and > 48 hours). Each of these 12 groups was analyzed for complications (minor inpatient complications included acute kidney injury, urinary tract infection, decubitus ulcer, and acute blood loss anemia, while major inpatient complications included sepsis or septic shock, pneumonia, acute respiratory failure, stroke, myocardial infarction, cardiac arrest, and deep vein thrombosis or pulmonary embolism), mortality rates, and hospital quality measures (length of stay and readmission rates). The results were compared across cohorts. A total of 2472 patients were identified: the mean age of the cohort was 80.6 ± 10.3 and was predominantly female (69%) and white (71%). The data demonstrated improved outcomes (complications, mortality rates, hospital quality measures) across all patients (non-risk stratified) for surgery within 24 hours compared to surgery between 24 hours and 48 hours and surgery greater than 48 hours (all outcomes p<0.050). However, these effects were not evenly distributed among the IRQ's. In the IRQ4 cohort, major complication rates progressed from 20% to 25% to 34% as a function of time to surgery (p=0.007). IRQ1 did not demonstrate similar results (p=0.756), with the rates essentially static across surgery time points (3% to 2% to 4%). A similar trend was seen when analyzing mortality at 1-year for highest risk patients, with similar 1-year mortality rates across operating room windows of IRQs 1-3 (IRQ1: p=0.061, IRQ2: p=0.259, IRQ3: p=0.524), but increased in IRQ4 with increasing time to surgery (21% vs 33% vs 33%, p=0.006). This study demonstrates a differential impact of expedited time to surgery on patients when stratified by risk profile. The lowest risk hip fracture patients do not fare worse if operated on within 48 hours as compared to 24 hours. III.

Acute Kidney Injury and Outcomes in Infants, Children, and Adolescents, Supported With Extracorporeal Life Support for Cardiopulmonary Failure

In neonatal and pediatric patients who require extracorporeal life support (ECLS), 60–70% develop acute kidney injury (AKI). Acute kidney injury has been associated with increased morbidity and mortality. We sought to describe our center’s experience with AKI in patients requiring ECLS and its effect on outcomes. We conducted a retrospective single-center study at an academic children’s hospital. All patients 0–18 years of age who required ECLS between January 2014 and December 2019. During the study period, there were 313 ECLS runs. The majority were neonates (66.8%) and 68.7% of runs were veno-arterial. Using Kidney Disease Improving Global Outcomes (KDIGO) criteria, 227 patients (72.5%) developed stage 2 or 3 AKI. The AKI group were younger (median age: 0.9 vs. 11.7 months, p &lt; 0.001), more likely to experience a hemorrhagic complication (46.9% vs. 31.9%, p = 0.0298), and had higher mortality rates (44.9% vs. 24.4%, p = 0.0009). Neonates who required ECLS were more likely to develop stage 2 or 3 AKI (78%) than pediatrics (63%) (p = 0.005). Adjusting for confounders, patients who developed AKI had 2.38 times higher odds of mortality (95% confidence interval [CI]: 1.34–4.25, p = 0.003). We conclude that the majority of patients requiring ECLS develop stage 2 or 3 AKI. Those with AKI were twice as likely to die when controlling for confounding variables. Multicenter and prospective evaluation of this modifiable risk factor is imperative to improve the care of this high-risk cohort.

Influence of the type of anaesthesia on acute kidney injury after nephrectomy: a randomised controlled trial.

Acute kidney injury develops frequently after nephrectomy, causing increased hospital duration of stay and mortality. Both propofol and volatile anaesthetic agents are thought to have renoprotective effects. We investigated whether the type of maintenance anaesthetic (propofol or desflurane) affected the incidence of acute kidney injury after nephrectomy. This single-centre, randomised controlled trial enrolled adult patients with renal cell carcinoma undergoing nephrectomy. In patients allocated to the propofol group, anaesthesia was induced and maintained using a target-controlled infusion of propofol. In patients allocated to the desflurane group, anaesthesia was induced with a bolus of thiopental and maintained with desflurane. Both groups received a target-controlled infusion of remifentanil during surgery. The primary outcome was the incidence of acute kidney injury within 7 postoperative days based on the serum creatinine component of the Kidney Disease: Improving Global Outcomes criteria. We analysed 317 patients (median (IQR [range]) age 62 (52-70 [26-85] y); 221 (70%) men). Postoperative AKI developed in 79 (25%) patients: 43 (27%) in the propofol group and 36 (23%) in the desflurane group (absolute risk difference (95%CI) 4.6 (-4.9-14.0%), p = 0.347). The severity of kidney injury was stage 1 in 76 patients, stage 2 in two patients and stage 3 in one patient. The type of anaesthetic maintenance drug (propofol vs. desflurane) did not affect the incidence of acute kidney injury after nephrectomy. Future research might be better directed towards investigating other potentially modifiable risk factors for postoperative acute kidney injury in this patient population.

Glucosamine mitigates ischemia-reperfusion-induced acute kidney injury through anti-inflammatory mechanisms

ObjectiveAcute kidney injury (AKI), a syndrome with high morbidity and mortality worldwide, frequently arises from renal ischemia-reperfusion (I/R) injury, particularly in surgical contexts. Despite extensive research, effective therapies for both AKI and its progression to renal interstitial fibrosis remain elusive. This study investigates the potential therapeutic efficacy of glucosamine (GS), an endogenous amino sugar, in alleviating I/R-induced AKI.MethodsA murine I/R injury model was utilized to evaluate the protective effects of GS. Mice were treated with GS prior to I/R injury, and renal tissues were harvested for biochemical, histological, and molecular analyses. Key markers of oxidative stress, mitochondrial integrity, and endoplasmic reticulum (ER) stress were measured. Additionally, inflammatory responses in proximal convoluted tubular epithelial cells exposed to TPHP, an environmental toxin, were assessed in vitro.ResultsGS administration markedly reduced oxidative stress levels, preserved mitochondrial structure, and mitigated ER stress in renal tissues following I/R injury. Moreover, GS significantly attenuated TPHP-induced inflammatory responses in proximal tubular epithelial cells, suggesting a targeted anti-inflammatory action.ConclusionThese findings highlight glucosamine’s potential as a therapeutic agent for AKI, offering protection through the modulation of oxidative, mitochondrial, and inflammatory pathways. This study provides foundational evidence for GS as a promising candidate for AKI intervention and opens avenues for further exploration of glucosamine in kidney disease therapeutics.

Comment on "Impact of Dexmedetomidine Dosing and Timing on Acute Kidney Injury and Renal Outcomes After Cardiac Surgery: A Meta-Analytic Approach".

Comment on "Impact of Dexmedetomidine Dosing and Timing on Acute Kidney Injury and Renal Outcomes After Cardiac Surgery: A Meta-Analytic Approach".

Focus on the evaluation and control of medical quality to implement high-quality CRRT

Continuous renal replacement therapy (CRRT) has become a crucial treatment for critical acute kidney injury (AKI) patients. With the widespread application of CRRT, the need for standardized evaluation and control of CRRT medical quality has emerged as a significant issue in nephrology and related fields. This article reviews the development of CRRT, from its origins to technological advancements and current widespread use, explores the framework for evaluating CRRT medical quality, emphasizes the importance of balancing efficacy and safety, and provides recommendations for improving medical quality including the formation of multidisciplinary teams and goal-directed renal replacement therapy to ensure the efficacy and safety.

Left Ventricular Apical Aneurysm in a Dog—A Case Report

The cadaver of a 16-year-old mixed-breed male dog was presented to the Faculty of Veterinary Medicine of IULS, Romania, after having been euthanized in a private practice at the owner’s request following acute cardio-respiratory failure. The necropsy revealed a left ventricular apical aneurysm with a bulging fibrous sac measuring about 0.7 cm/0.3 cm. The lesion involved all three structures of the cardiac wall, with mineralization areas and neovascularization. Immunohistochemistry showed strong positivity for desmin and weak positivity for CD-31 in the cardiac muscle fibers, positivity for α-sma in the smooth muscle cells of the vascular walls and positivity for vimentin in the cardiac stroma. MMP-2 and MMP-9 showed strong expression in the cardiomyocytes, whereas TIMP-1 showed positive immunoexpression only in the Eberth’s lines. To the authors’ knowledge, left ventricular apical aneurysm has only been reported once in dogs.

Innominate Artery Translocation with Hemiarch Replacement Strategy for Acute Type A Aortic Dissection: a Single-Center Study.

Aggressive surgical methods for acute type A aortic dissection (ATAD) can cause extended operating times and postoperative complications. less extensive techniques may increase the risk of needing further aortic reintervention. To prevent the need for extensive aortic arch surgery and subsequent re-sternotomy, hemiarch replacement (HAR) with innominate artery (a.) translocation is performed to create a suitable proximal landing zone for future endovascular repair. Retrospective study of 112 patients with ATAD who underwent aortic surgery from January 2009 to December 2020. Forty-one patients underwent HAR with innominate artery translocation, 16 underwent total arch replacement (TAR), and 55 underwent only HAR. Multivariable Cox regression and logistic regression analyses were used to study the outcomes and risk factors. The TAR group had a higher incidence of postoperative acute kidney injury. The overall mortality rate of the TAR group was 25%, compared with 20% in the HAR group and 14.6% in the translocation group. The 5-year overall survival rates for the groups were 81.9%, 75.0%, and 77.7%, respectively. False lumen thrombosis at the aortic arch and descending aorta level were factors associated with reduced mortality in both univariable and multivariable analyses. The translocation group had a significantly higher reintervention rate of 41.5% compared with the TAR and HAR groups, with rates of 31.3% and 16.4%, respectively. The median reintervention time for the translocation group was 4.72 years. Despite the innominate translocation technique having a higher reintervention rate, it had similar mortality outcomes to HAR and TAR. Thus, it could be a more convenient option for reintervention, including creating a proximal landing zone, which could benefit patients needing endovascular repair.

Association between early fluid balance and outcomes in patients receiving continuous renal replacement therapy for cardiac surgery-associated acute kidney injury

Objective: To evaluate the association between fluid balance within 48 hours after initiating continuous renal replacement therapy (CRRT) and 90-day mortality of patients with cardiac surgery-associated acute kidney injury (CSA-AKI). Methods: Adult patients who received CRRT for CSA-AKI for more than 24 hours between January 2016 and December 2021 in the First Affiliated Hospital of Nanjing Medical University were prospectively included. Exposures were fluid input, fluid output, fluid balance and percentage of fluid overload change (defined as weight-standardized fluid input/output difference) within 48 hours after CRRT initiation. The primary outcome was 90-day mortality. The relationship between the exposures and 90-day mortality was determined by restricted cubic spline and segmented Cox regression. Results: The study enrolled 262 patients, and 90-day mortality was 60.3% (158/262). There were 171 males and 91 females, with a median age of 64 (54, 71) years. The dead patients (n=158) had more fluid input [6.43 (5.62, 7.34) L vs 6.07 (5.09, 6.90) L, P=0.013], greater fluid balance [-0.01 (-1.36, 1.34) L vs -0.65 (-1.71, 0.42) L, P=0.005] and higher percentage of fluid overload change [-0.01% (-2.17%, 2.01%) vs -0.85% (-2.49%, 0.52%), P=0.013] within 48 hours after CRRT initiation than the survived patients (n=104). The cumulative fluid balance and fluid overload changes have a "J" curve relationship with 90-day mortality. Higher positive fluid balance (adjusted HR per 1 L increase above 0.5 L=1.33, 95%CI: 1.17-1.50) and greater proportion of fluid overload changes (adjusted HR per 1% increase above 0.7%=1.20, 90%CI: 1.11-1.30) were associated with an increased risk of death. Cumulative fluid input was linearly related to the 90-day mortality. Higher input (adjusted HR per 1 L increase=1.13, 95%CI: 1.03-1.24) was associated with an increased risk of death. The cumulative fluid output showed a U-shaped relationship with risk of death. Both lower output (adjusted HR per 1 L increase below 6.7 L=0.73, 95%CI: 0.58-0.90) and higher output (adjusted HR per 1 L increase above 6.7 L=1.24, 95%CI: 1.01-1.53) were associated with increased risk of death. Conclusion: In patients with CSA-AKI, excessive fluid input, insufficient or excessive output and a positive fluid balance or percentage of fluid overload change within the first 48 hours after CRRT initiation are associated with increased risk of 90-day mortality.

Tubular MYDGF Slows Progression of Chronic Kidney Disease by Maintaining Mitochondrial Homeostasis.

Mitochondrial dysfunction is a key event driving the maladaptive repair of tubular epithelial cells during the transition from acute kidney injury to chronic kidney disease (CKD). Therefore, identifying potential targets involved in mitochondrial dysfunction in tubular epithelial cells is clinically important. Myeloid-derived growth factor (MYDGF), a novel secreted protein, plays important roles in multiple cardiovascular diseases, but the function of MYDGF in tubular epithelial cells remains unknown. In the present study, it is found that MYDGF expression is significantly reduced in the cortex of the kidney, especially in the proximal tubules, from mice with CKD. Notably, lower expression of MYDGF is observed in tubules from patients with CKD and the level of MYDGF correlated with key factors related to kidney fibrosis and estimated glomerular filtration rate (eGFR) in patients with CKD. Tubule-specific deletion of Mydgf exacerbates kidney injury in mice with CKD; however, Mydgf overexpression attenuates kidney fibrosis by remodeling mitochondrial homeostasis in tubular epithelial cells. Mechanistically, renal tubular MYDGF positively regulates the expression of isocitrate dehydrogenase 2 (IDH2), restores mitochondrial homeostasis, and slows CKD progression. Thus, this study indicates that MYDGF derived from tubules may be an effective therapeutic strategy for patients with CKD.

Kidney and blood pressure outcomes 11years after pediatric critical illness and longitudinal impact of AKI: a prospective cohort study.

Acute kidney injury (AKI) is common in critically ill children and associated with adverse short-term outcomes; however, long-term outcomes are not well described. This longitudinal prospective cohort study examined the prevalence of chronic kidney disease (CKD) and hypertension (HTN) 11 vs. 6years after pediatric intensive care unit (PICU) admission and association with AKI. We examined children (age < 19years) without pre-existing kidney disease 11 ± 1.5years after PICU admission at a single center. AKI was defined using serum creatinine criteria. The primary outcome was a composite of CKD or HTN. CKD was defined as estimated glomerular filtration rate (eGFR) < 90mL/min/1.73 m2 or albuminuria. Multivariable analyses compared outcomes at 11- vs. 6-year follow-up and association with AKI during PICU admission. Of 96 children evaluated 11years after PICU admission, 16% had evidence of CKD or HTN (vs. 28% at 6years, p < 0.05). Multivariable analysis did not show improvement in outcomes from 6- to 11-year follow-up. eGFR decreased from 6- to 11-year follow-up (adjusted coefficient - 11.7, 95% CI - 17.6 to - 5.9) and systolic and diastolic blood pressures improved. AKI was associated with composite outcome at 6-year (adjusted odds ratio (aOR) 12.7, 95% CI 3.2-51.2, p < 0.001), but not 11-year follow-up (p = 0.31). AKI was associated with CKD (aOR 10.4, 95% CI 3.1-34.7) at 11years. This study provides novel data showing that adverse kidney and blood pressure outcomes remain highly prevalent 10years after critical illness in childhood. The association with AKI wanes over time.

Pregnancy-related acute kidney injury leads to hypertension, reduced kidney function and cognitive impairment in postpartum rats

IntroductionWomen with hypertensive disorders of pregnancy such as HELLP (hemolysis, elevated liver enzyme, low platelet) Syndrome are affected by acute kidney injury during pregnancy (PR-AKI) at higher rates than women without hypertension. Both hypertensive disorders of pregnancy and Acute Kidney Injury (AKI) outside the context of pregnancy have been associated with an increased risk of developing Chronic Kidney Disease (CKD) and cognitive impairment. In our current study, we set out to determine if PR-AKI led to the development of CKD and impaired cognition in the postpartum period and if HELLP syndrome exacerbates the impairments.MethodsUsing timed-pregnant Sprague Dawley rats, on gestational day (GD) 12, mini-osmotic pumps infusing anti-angiogenic factors were surgically placed in the intraperitoneal cavity to induce HELLP. On GD18, AKI was induced via bilateral renal reperfusion ischemia surgery. Mean arterial pressure and birth outcomes were used to assess the global effects of AKI, and liver enzymes were used to assess HELLP. CKD was assessed by measuring glomerular filtration rate (GFR), urinary output, and renal fibrosis. Anxiety-like behaviors, object recognition memory, spatial memory, and avoidance memory were assessed via behavioral experiments.ResultsHELLP + AKI rats demonstrated more evidence of renal injury, hypertension, and behavioral deficits compared to normal pregnant animals. In addition, AKI had a negative impact on birth outcomes and maternal survival.ConclusionHELLP + AKI together led to evidence of persistent hypertension, progressive renal dysfunction, and cognitive impairment, which were exacerbated compared to AKI or HELLP alone. These findings suggest that PR-AKI in the presence of a hypertensive disorder of pregnancy, such as HELLP, leads to the development of CKD, cognitive dysfunction, and hypertension.

Clinical Impact of Admission Day on Outcomes in Acutely Decompensated Aortic Stenosis: A Nationwide Analysis

Background/Objectives: Aortic stenosis (AS) is a critical valvular heart disease associated with significant morbidity and mortality if not managed promptly. Previous studies have highlighted the “weekend effect”, where the day of admission impacts outcomes in various cardiac conditions. This study evaluates the impact of weekend versus weekday admissions on outcomes in patients admitted with acutely decompensated aortic stenosis. Methods: We conducted a retrospective cohort study using the National Inpatient Sample database, focusing on patients emergently admitted with decompensated aortic stenosis. Patient outcomes were compared between those admitted on weekends (midnight Friday to midnight Sunday) and weekdays. Results: Among 94,320 patients included, 4537 (4.81%) were admitted on weekends. Weekend admissions were associated with significantly higher mortality (aOR 1.86; 95% CI 1.27–2.74) and longer hospital stays (mean increase 3.18 days; p &lt; 0.001) compared to weekday admissions. Complication rates were also higher on weekends, including cardiogenic shock (aOR 2.1; 95% CI 1.54–2.87; p &lt; 0.001), acute kidney injury (aOR 2.48; 95% CI 2.09–2.94; p &lt; 0.001), and acute respiratory failure (aOR 2.88; 95% CI 2.38–3.49; p &lt; 0.001). Additionally, weekend admissions had lower rates of transcatheter aortic valve replacement (TAVR) (aOR 0.49; 95% CI 0.40–0.62; p &lt; 0.01) than weekday admissions. Conclusions: Patients with aortic stenosis admitted on weekends face significantly higher mortality, extended hospital stays, and increased complication rates compared to weekday admissions. Transcatheter aortic valve replacement (TAVR) rates were also lower for patients admitted on weekends. The “weekend effect” markedly influences outcomes, underscoring the need for hospital and administrative strategies to mitigate these adverse effects. Implementing standardized protocols and optimizing resource allocation during weekends could potentially reduce mortality and improve patient outcomes, offering a path to more equitable healthcare delivery.

Fibronectin type III domain containing protein 5/irisin alleviated sepsis-induced acute kidney injury by abating ferroptosis through the adenosine 5'-monophosphate-activated protein kinase/nuclear factor erythroid-2-related factor 2 signaling pathway

Objective: Ferroptosis has been described in association with acute kidney injury (AKI)-induced sepsis. Fibronectin type III domain containing protein 5 (FNDC5)/irisin plays a crucial role in renal protection. The objective of this study was to investigate whether FNDC5/irisin is involved in AKI-induced sepsis by modulating ferroptosis, and the molecular mechanisms that may be involved. Material and Methods: A sepsis-induced AKI model was built in vivo and in vitro through lipopolysaccharide (LPS) intervention. FNDC5, adenosine 5'-monophosphate-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), glutathione peroxidase 4 (GPX4), and acyl-CoA synthetase long-chain family member 4 (ACSL4) concentrations in cells and mouse kidney tissues were appraised by Western blot. Pro-inflammatory cytokines concentrations in cell supernatants and mouse kidney tissues were appraised by enzyme-linked immunosorbent assay. Fe2+ concentration in cells and mouse kidney tissue was appraised by kit. The apoptosis rate of cells and mouse kidney tissue was measured by flow cytometry. Automatic biochemical analyzer was to test serum creatinine (SCr) and blood urea nitrogen (BUN). The kidney tissue sections from each groups were observed by hematoxylin and eosin staining. Results: LPS abated FNDC5 concentration in human kidney-2 cells and mouse kidney tissue (P &lt; 0.001). Overexpression of FNDC5 can abated proinflammatory cytokines concentrations in cells and mouse kidney tissue (P &lt; 0.01). Meanwhile, overexpression of FNDC5 can boost GPX4 protein concentration, abate ACSL4 protein, and abate Fe2+ concentration in cells and mouse kidney tissues (P &lt; 0.05). In addition, the overexpression of FNDC5 can reduce the rate of apoptosis (P &lt; 0.01). In vivo experiments showed that FNDC5 overexpression reduced serum BUN and SCr concentrations and alleviated pathological damage in the mouse renal tissues (P &lt; 0.05) and exhibited a certain renal protective effect. FNDC5 overexpression can boost p-AMPK/AMPK, Nrf2, and HO-1 protein concentrations (P &lt; 0.01). Conclusion: FNDC5/irisin improves sepsis-induced acute renal injury by abating ferroptosis through the AMPK/Nrf2 signaling pathway.

Signal pathways involved in contrast-induced acute kidney injury

Contrast-induced acute kidney injury (CI-AKI) has emerged as a global public health concern, ranking as the third most prevalent cause of hospital-acquired acute kidney injury, which is related to adverse outcomes. However, its precise pathogenesis remains elusive. Consequently, researchers are dedicated to uncovering CI-AKI’s pathophysiology and signaling pathways, including inflammation, oxidative stress, apoptosis, and ferroptosis, to improve prevention and treatment. This review thoroughly analyzes the signaling pathways and their interactions associated with CI-AKI, assesses the impact of various research models on pathway analysis, and explores more precise targeted treatment and prevention approaches. Aims to furnish a robust theoretical foundation for the molecular mechanisms underpinning clinical treatments.

CTCA Prior to Invasive Coronary Angiography in Patients With Previous Bypass Surgery: Patient-Related Outcomes, Imaging Resource Utilization, and Cardiac Events at 3 Years From the BYPASS-CTCA Trial.

In patients with previous coronary artery bypass grafting, computed tomography cardiac angiography (CTCA) before invasive coronary angiography (ICA) was demonstrated in the BYPASS-CTCA trial (Randomized Controlled Trial to Assess Whether Computed Tomography Cardiac Angiography Can Improve Invasive Coronary Angiography in Bypass Surgery Patients) to reduce procedure time and incidence of contrast-associated acute kidney injury, with greater levels of patient satisfaction. Patient-related outcomes, utilization of further diagnostic imaging resources, and longer-term incidence of major adverse cardiac events were key secondary end points not yet reported. Patients with prior coronary artery bypass grafting referred for ICA were randomized 1:1 to undergo CTCA before ICA or ICA alone and followed up for a median of 3 (2.2-3.4) years. Angina status was assessed using the Seattle Angina Questionnaire and overall quality of life using the EQ-5D-5L. The incidence of noninvasive imaging use and major adverse cardiac events were compared between the 2 groups. In all, 688 patients were randomized, 344 to CTCA+ICA and 344 to ICA only. The mean age of participants was 69.8 years, with 45% undergoing ICA for acute coronary syndromes and the remainder stable angina. At 3 months follow-up, patients in the CTCA+ICA group were more likely to be angina-free (51.7% versus 43.2%; P=0.03) with greater quality of life (EQ-5D-5L index, 81.6 versus 74.4; P=0.001), although these improvements did not persist. At 3 years follow-up, imaging resource use (35.8% versus 45.1%; odds ratio, 0.68 [95% CI, 0.50-0.92]; P=0.013) and incidence of major adverse cardiac events were lower in the CTCA+ICA group (35.8% versus 43.5%; hazard ratio, 0.73 [95% CI, 0.58-0.93]; P=0.010). In patients with prior coronary artery bypass grafting undergoing ICA, CTCA before ICA leads to reductions in the use of imaging resources and the rate of major cardiac events out to 3 years, but with similar patient-related outcome measures. Together with the initial findings of BYPASS-CTCA, these data are supportive of routinely undertaking a CTCA before ICA in patients with prior coronary artery bypass grafting. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03736018.

The Effects of Syphilis Infection on Total Knee Arthroplasty Outcomes: A Retrospective Cohort Study

Objective: This study investigated the impact of recent syphilis infection on postoperative outcomes following total knee arthroplasty (TKA). We hypothesized that patients with a documented history of syphilis infection would experience a higher rate of postoperative complications compared to those without such a history. Methods: We conducted a retrospective cohort analysis using a national insurance claims database. Our study population included 237,360 patients who underwent primary TKA between 2005 and 2024. Patients were classified into two groups based on the presence (+Syph) or absence (−Syph) of a syphilis diagnosis within one year prior to the TKA. We evaluated the rates of several postoperative complications at 30 days postsurgery, including infection, hematologic issues, and cardiac events. Statistical analyses between groups was performed using chi-squared tests and Fisher’s exact tests. Routine demographic data such as age, sex, race, and comorbidities were also analyzed. Results: Among the 237,360 TKA patients, we identified 71 with a history of syphilis within one year of their surgery. The +Syph group exhibited significantly higher rates of periprosthetic infection (4.23% vs. 0.81%, p = 0.001), need for manipulation under anesthesia (MUA) at four months (7.04% vs. 2.82%, p = 0.032), deep venous thrombosis (4.23% vs. 1.27%, p = 0.026), periprosthetic fracture (2.82% vs. 0.23%, p &lt; 0.001), and pneumonia (2.82% vs. 0.62%, p = 0.019) within 30 days postTKA. No significant differences were observed in 30-day mortality, deep or superficial surgical site infections, wound dehiscence, blood loss anemia, or transfusion requirements. Additionally, rates of acute renal failure, pulmonary embolism, and cardiac events did not differ significantly between groups. Demographically, patients in the syphilis cohort had a higher prevalence of smoking and diabetes preoperatively within one year of their surgical date. Conclusions: A documented syphilis diagnosis within one year of TKA significantly affects postoperative outcomes, increasing the rates of prosthetic joint infection, MUA, deep venous thrombosis, periprosthetic fracture, and pneumonia. These findings underscore the need for heightened vigilance in the pre- and postoperative management of patients with a history of syphilis infection undergoing TKA. Further research is warranted to explore the relationship between prior syphilis infection and TKA outcomes, as well as to develop strategies to mitigate this increased risk.

Dexmedetomidine inhibits ferroptosis and attenuates sepsis-induced acute kidney injury via activating the Nrf2/SLC7A11/FSP1/CoQ10 pathway

ABSTRACT Objectives The molecular mechanism underlying the protective effects of DEX against sepsis-induced acute kidney injury (SAKI) remains to be elucidated. Methods We established S-AKI models in vivo via CLP and in vitro with LPS-induced HK-2 cells. Results The Nrf2/SLC7A11/FSP1/CoQ10 pathway was inhibited in S-AKI both in vitro and in vivo. The overexpression of Nrf2 inhibited LPS-induced ferroptosis by activating the SLC7A11/FSP1/CoQ10 pathway. DEX ameliorated kidney tissue damage, as determined by a decrease in BUN, Cr, and inflammatory factor levels, along with renal tubule vacuolation and inflammatory cell infiltration in S-AKI mice. Additionally, DEX treatment significantly ameliorated ferroptosis in S-AKI in vitro and in vivo, as indicated by an improvement in mitochondrial shrinkage and disruption of cristae, a decrease in iron, ROS, MDA, and 4-HNE levels, and an increase in GSH and GPX4 levels. Mechanistically, DEX treatment restored the reduction of Nrf2 expression and nuclear translocation in S-AKI, as well as, the levels of downstream SLC7A11, FSP1, and CoQ10. Knocking down Nrf2 in vitro and administering brusatol in vivo eliminated the protective effect of DEX against S-AKI. Conclusions DEX mitigated ferroptosis and attenuated S-AKI by activating the Nrf2/SLC7A11/FSP1/CoQ10 pathway. Abbreviation: CLP: Cecal ligation puncture; LPS: Lipopolysaccharide; Nrf2: Nuclear factor-erythroid- 2-related factor 2; SLC7A11: Solute carrier family 7 member 11; FSP1: Ferroptosis suppressor protein 1; CoQ10: Coenzyme Q10; BUN: Blood urea nitrogen; Cr: Serum creatinine; ROS: Reactive oxygen species; MDA: Malondialdehyde; 4-HNE: 4-hydroxynonenal; GSH: Hlutathione; GPX4: Glutathione peroxidase 4.