Acute Failure Research Articles

Predictors for Irreversibility of Contrast-Induced Acute Kidney Injury in Patients with Obesity After Contrast-Enhanced Computed Tomography Coronary Angiography

Predictors for Irreversibility of Contrast-Induced Acute Kidney Injury in Patients with Obesity After Contrast-Enhanced Computed Tomography Coronary Angiography

Association of Serum Ferritin Levels with Short-Term Mortality Risk in Sepsis-associated Acute Kidney Injury: A Retrospective Cohort Study

： Background: This study aimed to assess the prognostic significance of serum ferritin levels in sepsis-associated acute kidney injury (SA-AKI) and their correlation with short-term mortality. Despite the established predictive value of serum ferritin in various serious diseases, its specific prognostic relevance in SA-AKI remains unexplored. Therefore, this study aimed to fill this research gap by investigating the association between serum ferritin levels and short-term mortality in patients diagnosed with SA-AKI. Methods: This retrospective cohort study used clinical information from the Medical Information Mart for Intensive Care-IV(MIMIC-IV) database to include all patients with SA-AKI admitted to the Intensive Care Unit(ICU) for the first time. The relationship between serum ferritin levels and 28-day mortality was explored using restricted cubic splines. Kaplan Meier curves and Cox regression models were utilized to evaluate the association between serum ferritin levels and mortality. Subgroup analysis is used to verify the stability of previous results. Results: In this study, a total of 878 patients (486 males and 392 females) with a median age of 63.7 years were enrolled. The results showed that increasing serum ferritin levels were linearly associated with a gradual increase in 28-day mortality rates. Specifically, the highest quartile group had a significantly higher 28-day mortality compared to the reference group (the first ferritin quartile). After adjusting for various factors, the fully adjusted hazard ratios (HRs) were calculated to be 1.92 (95% CI: 1.25~2.97, p=0.003). Conclusion: In patients with SA-AKI, higher serum ferritin levels are associated with an increased 28-day mortality rate.

Can Novel Biomarkers Effectively Predict Acute Kidney Injury in Liver or Kidney Transplant Recipients?

Acute kidney injury (AKI) constitutes a common complication associated with liver or kidney transplantation, which may significantly impact the graft condition and perioperative mortality. Current AKI diagnostic criteria based on serum creatinine (sCr) and urine output alterations are widely utilized in routine clinical practice. However, the diagnostic value of sCr may be limited by various confounding factors, including age, sex, reduced or increased muscle mass, and pre-existing chronic kidney disease (CKD). Furthermore, sCr is rather a late indicator of AKI, as its concentration tends to increase only when the severity of the injury is enough to decrease the estimated glomerular filtration rate (eGFR). Recent expertise highlights the need for novel biomarkers in post-transplantation AKI diagnosis, prediction of event-associated mortality, or evaluation of indications for renal replacement treatment (RRT). Over the last decade, the diagnostic performance of various AKI biomarkers has been assessed, among which some showed the potential to outperform sCr in AKI diagnosis. Identifying susceptible individuals, early diagnosis, and prompt intervention are crucial for successful transplantation, undisturbed graft function in long-term follow-up, and decreased mortality. However, the research on AKI biomarkers in transplantation still needs to be explored. The field lacks consistent results, rigorous study designs, and external validation. Considering the rapidly growing prevalence of CKD and cirrhosis that are associated with the transplantation at their end-stage, as well as the existing knowledge gap, the aim of this article was to provide the most up-to-date review of the studies on novel biomarkers in the diagnosis of post-transplantation AKI.

Carnosol alleviates cisplatin–induced acute kidney injury by regulating apoptosis and pyroptosis

AbstractThe use of the common anticancer drug cisplatin (CP) in clinical practice often leads to acute kidney injury (AKI); however, no protective therapy is available. Therefore, new drugs that reduce the nephrotoxicity induced by CP are urgently needed. Carnosol (CA) is an antioxidant found. We investigated the renoprotective effects of CA on CP‐induced AKI in male C57BL/6 mice and HK2 cells. CA mitigated renal dysfunction, histopathological changes and tubular injury in vivo, as indicated by the expression of NGAL, KIM1 and HMGB1. Moreover, the numbers of apoptotic cells and the expression of apoptotic proteins were dramatically reduced after CA treatment in mouse kidneys and HK2 cells. CA significantly ameliorated CP‐induced inflammation and decreased TNF‐α and IL‐1β levels in vivo and in vitro and macrophage infiltration in the mouse kidney. CA decreased the expression levels of p‐p65/p65, NLRP3 and ASC, which indicates that CA suppressed the activation of the NF‐κB/NLRP3 signaling axis induced by CP in vivo and in vitro. In addition, CA decreased the levels of certain protein in pyroptotic cells, as indicated by the expression of cleaved caspase‐1, GSDMD, and mature IL‐1β and IL‐18 in vivo and in vitro. Finally, CA reduced the level of cleaved caspase‐1, but those of GSDMD and NLRP3 protein were not significantly different after treatment with the NLRP3 inhibitor MCC950 and were elevated by the NLRP3 activator nigericin. In conclusion, this study revealed that CA protects against CP‐induced AKI by decreasing apoptosis and NF‐κB/NLRP3/GSDMD‐mediated pyroptosis, which provides new insight into the prevention of AKI.

Rhabdomyolysis Without Acute Kidney Injury in a 14-Year-Old Child With a Sedentary Lifestyle

Rhabdomyolysis Without Acute Kidney Injury in a 14-Year-Old Child With a Sedentary Lifestyle

Ketamine attenuates kidney damage and depression-like behaviors in mice with cisplatin-induced acute kidney injury

Acute kidney injury (AKI) is a serious condition characterized by decreased urine output, often accompanied by psychiatric symptoms like depression. However, there are limited pharmacological treatments available for AKI and its associated depressive symptoms. In this study, we investigated whether cisplatin-induced AKI in mice leads to depression-like behaviors and whether ketamine could alleviate both the kidney injury and these behaviors. Mice with cisplatin-induced AKI exhibited elevated levels of creatinine and urea, kidney damage, increased kidney injury molecule-1 protein, and pathological changes in the liver, colon, and spleen. They also showed depression-like behaviors and reduced expression of synaptic proteins in the prefrontal cortex. Remarkably, a single dose of ketamine significantly reduced these symptoms and pathological changes. Interestingly, the beneficial effects of ketamine on the kidneys, other organs, and depression-like behaviors, were reversed by the tropomyosin receptor kinase B (TrkB) inhibitor ANA-12. Western blot analysis revealed the involvement of the TrkB and ERK (extracellular signal-regulated kinase)-CREB (cAMP response element binding protein) signaling pathway. Additionally, metabolomics analysis indicated that blood metabolites, such as C16-ceramide, may contribute to the effects of ketamine in this model. These findings suggest that cisplatin-induced nephrotoxicity in AKI mice contributes to depression-like behaviors, and ketamine can alleviate both kidney damage and depression-like symptoms by modulating the TrkB and ERK-CREB signaling pathways, as well as altering blood metabolites. However, the role of the kidney-brain axis in these depression-like behaviors remains unclear. Furthermore, ketamine may have therapeutic potential for treating kidney diseases such as AKI, along with associated depressive symptoms.

Sacituzumab-govitecan-induced severe acute tubulointerstitial nephritis requiring hemodialysis

BackgroundSacituzumab govitecan is an antibody-drug conjugate that is FDA approved for refractory metastatic triple-negative breast cancer. It targets the human trophoblastic cell-surface antigen 2 (Trop-2) with SN-38, a topoisomerase I inhibitor, attached to the antibody [1]. SN-38 breaks DNA strands and induces tumor apoptosis [2]. Acute kidney injury (AKI) is one of its adverse effects mainly prerenal due to gastrointestinal toxicity, but it has not been reported to cause acute tubulointerstitial nephritis (ATIN).Case PresentationThis report describes a rare adverse effect of sacituzumab govitecan, the approach to diagnosing the etiology of the patient’s AKI, and the mechanism by which sacituzumab govitecan causes ATIN. A woman with metastatic ER positive, PR positive, HER2 negative breast cancer who was initiated on sacituzumab govitecan presents with vomiting and diarrhea, and findings of nephrotic-range proteinuria, negative anti-PLA2R antibody, and severe AKI requiring hemodialysis. She underwent kidney biopsy and pathology showed ATIN characterized by patchy interstitial inflammation alongside tubular injury without glomerular and vascular involvement. With intermittent renal replacement therapy, furosemide challenge, and a course of prednisone, the patient’s kidney function recovered.ConclusionsSacituzumab has a high affinity for Trop-2 protein which is also expressed within the collecting ducts, and to a lesser extent, the proximal tubule. Individuals, such as this patient, who express a homozygous genotype for UGT1A1*28 allele are at increased risk for AKI from sacituzumab govitecan due to decreased glucuronidation of SN-38.

Chyme reinfusion therapy in adults with severe acute intestinal failure: A descriptive cohort study

AbstractBackgroundChyme reinfusion therapy treats patients with high‐output fistulas or stomas by returning chyme to the distal gut. The role of this treatment in severe acute intestinal failure is currently unclear. The primary outcome of this study was a successful establishment of chyme reinfusion therapy, defined by the ability to replace parenteral nutrition for nutrition support.MethodsA descriptive cohort study of adult patients with severe acute intestinal failure due to a high‐output stoma and distal mucus fistula or a high‐output small intestinal fistula receiving chyme reinfusion therapy was undertaken. The effect of chyme reinfusion therapy on parenteral nutrition requirements, medication, nutrition status, liver function, and treatment cost were studied.ResultsTwenty‐four patients commenced treatment for a median of 44 (range, 3–571; total, 2263) days. Fifteen (62.5%) were successfully established for 1208 days, and nine continued treatment at home. Parenteral requirements, including volume, energy and nitrogen content, and frequency, were significantly reduced (P = 0.002), whereas anthropometric measurements remained stable. However, chyme therapy was not tolerated in nine patients (37.5%), and only two (8.3%) weaned fully from parenteral nutrition. Chyme reinfusion therapy was associated with a 47.6% reduction in parenteral energy requirements, 42.8% reduction in nitrogen, and 33.3% reduction in volume of parenteral nutrition requirements. Treatment was associated with a net cost of £30.05 ($40.27) per patient per day.ConclusionChyme reinfusion therapy was associated with reductions in the need for parenteral therapy and medication but did not replace parenteral nutrition or result in a significant cost saving.

Effect of thread direction on rotational stability in lag‐screw fixation of sacroiliac luxation: An ex vivo cadaveric study in small‐breed dogs

AbstractObjectiveTo assess the effect of screw thread direction on rotational resistance in canine sacroiliac (SI) luxation models using left‐ and right‐handed screws.Study designControlled laboratory study.Sample populationTwenty‐four adult canine pelves with proximal femora were examined.MethodsFour groups (n = 6 each) were established: right‐handed screw/right SI luxation (RhRSI), right‐handed screw/left SI luxation (RhLSI), left‐handed screw/left SI luxation (LhLSI), and left‐handed screw/right SI luxation (LhRSI). Under fluoroscopy, 2.4 mm cortical screws were placed into the SI joint in a lag fashion. An acute failure test measured force and torque at yield and peak points, with the ilium and femur positioned at a 108° angle and displacement at 0.099 cm/s. Torque (N cm) was calculated from force (N) and the moment arm (cm).ResultsDifferences in median torque were found at yield and peak points. RhRSI gave 50.08 N cm versus 16.01 N cm for RhLSI (p < .01), and LhLSI showed 39.42 N cm versus 19.93 N cm for LhRSI (p < .03). At peak, RhRSI recorded 67.55 N cm compared to 28.14 N cm for RhLSI (p < .01), and LhLSI reached 51.79 N cm versus 28.28 N cm for LhRSI (p < .05). All samples failed by rotation without screw breakage or fractures.ConclusionRight‐handed screws provided greater rotational resistance in right‐sided luxation, and left‐handed screws in left‐sided luxation, which demonstrated that screw thread direction influenced fixation stability in SI luxation.Clinical significanceThe findings suggest that selecting screw thread direction can enhance biomechanical stability in SI luxation repair, improving surgical outcomes for affected dogs.

Incidence and risk factors of acute kidney injury in redo cardiac surgery: a single center analysis

The incidence, risk factors and prognostic implications of acute kidney injury (AKI) in patients undergoing redo cardiac surgery are still poorly defined. We prospectively collected data on 394 consecutive redo patients between January 2011 and October 2020. Patients were divided into groups according to the occurrence of different degrees of postoperative AKI (No AKI vs. Any AKI; No AKI-AKI 1 vs. AKI 2–3). The relationship between AKI and other major complications was also investigated. Postoperatively, AKI 1 occurred in 124 (31.5%), AKI 2 in 36 (9.1%) and AKI 3 in 64 (16.2%). Higher KDIGO classes were associated with increased in-hospital mortality: 5.3% among patients with no postoperative AKI and 8.9%, 13.9% and 64.1% in patients with AKI 1, 2 and 3, respectively (p < 0.001). Age, baseline hemoglobin, comorbidity, EuroSCORE II, operative time and transfusion during CPB proved to be significantly associated to the occurrence of AKI. Our study confirms the burden and prognostic role of AKI in a large, all comers, single center database of redo cardiac procedures.

Sepsis-Associated Acute Kidney Injury in Critically Ill Children: Incidence and Outcomes

Background: Acute kidney injury (AKI) is a major concern in pediatric critical care, often occurring in conjunction with sepsis. This study aimed to identify the incidence, outcomes, and risk factors for AKI in the context of pediatric sepsis. Methods: This was a bicentric retrospective cohort study conducted at two university hospitals in Saudi Arabia. All patients aged 1 month to 14 years admitted to pediatric intensive care units (PICUs) with evidence of sepsis between January 2021 and December 2022 were included. AKI was defined and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Demographic, clinical, and laboratory data were collected from electronic medical records. Results: 309 patients were included, 38 (12.3%) developed stage 1 AKI, 64 (20.7%) developed stage 2 AKI, and 183 (59.2%) developed stage 3 AKI. Patients with sepsis-associated AKI had significantly longer PICU stays and higher mortality rates than those without AKI (p &lt; 0.01). Inflammatory markers and certain medications were associated with increased AKI risk. Factors independently associated with stage 3 AKI include younger age, positive blood culture, gentamycin use, and higher SOFA score. Conclusions: Sepsis-associated AKI is a common and serious complication in critically ill children, contributing to increased morbidity and mortality. Identification of specific risk factors may facilitate early recognition and targeted interventions to mitigate the impact of AKI in this vulnerable population.

Early Acute Kidney Injury in Stroke Patients Submitted to Endovascular Treatment: A Cohort Study

Background/Objectives: Acute kidney injury (AKI) is a potential complication of cardiovascular disorders and is associated with worse outcome. The aim of this study was to assess the incidence of early AKI after endovascular therapy for acute ischemic stroke, identify predictors for this complication, and test the association between AKI and mortality or death or dependency. Methods: This was a single-center cohort study involving consecutive patients with acute ischemic stroke submitted to endovascular therapy between 2015 and 2022. AKI was defined according to the KDIGO criteria and evaluated at 48 h. Other outcomes of interest were vital status and functional dependency at 3 months using the modified Rankin Scale, with death or dependency being defined as a score &gt; 2. An adjustment for potential confounders was performed using logistic regression. Results: Overall, 1150 patients were included in the analysis, with a mean age of 74 years and a slight female preponderance (56%). The median NIHSS was 15, the mean onset-to-groin time was 392 min, and 92% of patients were successfully recanalized. The overall incidence rate of AKI was 6%. On univariate analysis, patients with AKI were older (p = 0.002), had a longer time to EVT (p = 0.042), higher NIHSS (p = 0.006), higher blood glucose (p = 0.033), and lower baseline glomerular filtration rate (GFR) (p &lt; 0.001). After adjustment for confounders, AKI was independently associated with NIHSS (p = 0.012), time to treatment (p = 0.004), and lower baseline GFR (p &lt; 0.001). AKI was also independently associated with higher mortality (OR = 2.302, p = 0.003). Conclusions: Patients with impaired baseline renal function and more severe stroke are at higher risk of AKI, and AKI begets worse stroke outcome. Better strategies are required to optimize treatment outcome in these patients and avert this vicious cycle.

Ultrasmall Black Phosphorus Quantum Dots with Robust Antioxidative Properties for Acute Kidney and Liver Injury Therapy.

Acute organ injuries, such as acute kidney injury (AKI) and acute liver injury (ALI), usually present high morbidity and mortality in patients. However, the current clinical treatments remain limited, especially the lack of effective drug-based treatment. Since these acute injuries are often associated with reactive oxygen species (ROS) overproduction, it is a promising strategy to develop therapeutic agents with potent ROS scavenging ability and excellent biocompatibility for efficient antioxidation therapy. Black phosphorus quantum dots (BPQDs), low-dimensional nanomaterials prepared through a straightforward one-step method and capable of complete controllable biodegradation, offer significant potential. This study comprehensively explores the extensive free-radical scavenging capabilities of BPQDs, underscoring their immense potential in treating ROS-related organ injuries. BPQDs could simultaneously achieve radical scavenging of DPPH, ABTS·, OH·, and O2 -· and exhibit excellent cytoprotective effects against ROS-mediated damage even at extremely low dosages. Besides, the ultrasmall size of BPQDs (≈3-5nm) allows them to effectively penetrate the glomerular filtration barrier (≈6nm), significantly improving the symptoms of AKI and ALI in vivo. The therapeutic efficacy and great biocompatibility of BPQDs facilitate the clinical management of ROS-related diseases, which will broaden the applications of QDs in the field of biomedicine.

New Therapeutic Method for Alleviating Damage of Acute Kidney Injury Through BCL-2 Gene Promoter I-Motif

Acute kidney injury (AKI) is a global public health problem with its pathogenesis not fully understood. Excessive apoptosis of renal tubular epithelial cells is an important feature of AKI patients, and therefore an anti-apoptotic approach could be used in the treatment for AKI. Up-regulation of B-cell lymphoma-2 (BCL-2) gene and protein has been found to be correlated with anti-apoptosis of cells. It has been found that the presence of the C-rich sequence on the upstream region of the BCL-2 gene promoter could form DNA secondary i-motif structure, and its stabilization by small molecules could up-regulate gene transcription and translation. In the present study, we constructed AKI models through folic acid (FA) induction. With these in vitro and in vivo models, we demonstrated that the acridone derivative A22 could up-regulate the expression of BCL-2 by targeting its gene promoter i-motif to reduce renal tubular epithelial cell apoptosis and improve renal function in many ways. A22 could alleviate FA-induced oxidative stress injury, inflammatory response, and endoplasmic reticulum stress in mouse kidneys. Our results provided a potentially new anti-apoptotic approach for the treatment of early stages of AKI. Our employed model focused on its short-term effect on AKI, while its long-term efficacy and safety, particularly regarding the regeneration of renal tubular epithelial cells, require further investigation before clinical application. This study further demonstrated that promoter i-motif could be targeted for up-regulating BCL-2 expression for the treatment of important diseases caused by excessive apoptosis.

Assessing acute kidney injury risk after COVID vaccination and infection in a large cohort study

Acute kidney injury (AKI) has been noticed after both COVID-19 vaccination and infection, affecting risk-benefit evaluations and vaccine hesitancy. We conducted a large-scale N3C cohort study to compare AKI incidence following COVID-19 vaccination and infection. Participants from December 2020 to August 2023 were divided into two groups based on their initially observed COVID-19 antigen exposure: COVID-19 vaccination group (n = 2,953,219) and COVID-19 infection group (n = 3,616,802). AKI was defined by diagnostic codes and serum creatinine changes within a 30 day follow-up window after exposure. The absolute risk of AKI was 0.66% in the vaccination group versus 4.88% in the infection group. After adjusting for various confounders, COVID-19 infection was associated with a significantly higher risk of AKI than COVID-19 vaccination (aHR = 10.31, P < 0.001). Our study reveals that COVID-19 vaccination is associated with a significant lower AKI risk compared to COVID-19 infection.

The Effect of Diabetes Mellitus Severity on Foot &amp; Ankle Burn Recovery

Background: Diabetic patients often present with complex limb pathology, resulting in impaired sensation in the distal extremities making tactile injuries such as burns difficult to notice. We posit that poorly controlled diabetes mellitus, evidenced by increasing elevations in hemoglobin A1c, is associated with delayed wound healing and increased complications in burn patients. Methods: The TriNetX Network, a database of 89 million patients across the U.S., was queried for diabetic patients with foot and ankle burns. Patients were divided into four groups based on A1c: properly controlled (&lt;7%), moderately controlled (7–9%), poorly controlled (&gt;9%), and propensity-matched non-diabetic controls. Evaluated outcomes included split-thickness skin grafting, infections, amputations, acute kidney failure (AKF), and mortality within one month of the burn. Results: When comparing the poorly controlled A1c cohort with the properly controlled and moderately controlled A1c cohorts, we found a significant increase in amputations (p = 0.042) and cutaneous infections (p = 0.0438), respectively. When evaluating non-diabetics to diabetic patients, significantly increased rates of amputations (p &lt; 0.0001), cutaneous infections (p = 0.0485), systemic infections (p = 0.0066), and AKF (p = 0.0005) were noted in the latter. Conclusions: Poorly controlled diabetes shows a significant correlation with increased complications following foot and ankle burns, including amputations, infections, and AKF.

An audit of the adherence to dosing and therapeutic monitoring of intravenous vancomycin in accordance with the trust’s antimicrobial guidelines

Abstract Introduction Inappropriate vancomycin dosing and monitoring have compromised patient safety, causing acute kidney injury and prolonged hospital stays. Misuse of antibiotics, like vancomycin, accelerates resistance, a global health threat. Following guidelines can prevent harm and curb the emergence of vancomycin-resistant enterococci and resistant Staphylococcus aureus1. Aim To assess the level of adherence to trust guidelines for the dosing and monitoring of intravenous vancomycin. Audit Standards Standard 1: Patients prescribed intravenous vancomycin should have documented indication Standard 2: Patients prescribed intravenous vancomycin should have correct loading dose Standard 3: Patients prescribed intravenous vancomycin should have correct maintenance dose Standard 4: Patients prescribed intravenous vancomycin should have trough levels taken at the right time Standard 5: Patients prescribed intravenous vancomycin should have doses accurately adjusted against trough level Results: Standard 6: Patients prescribed intravenous vancomycin should have all prescribed doses administered (i.e. no missed doses). Standard 7: Vancomycin prescriptions should be screened by a pharmacist. Methods This audit was approved by both the Trust Clinical Audit Committee and the Antimicrobial Stewardship Group. A retrospective audit using data extracted from EPMA. The data collected included: indication documented (Yes/No), correct loading dose? (Yes/No), missed doses? (Yes/No), correct maintenance dose? (Yes/No), correct first sampling? (Yes/No), correct subsequent sampling? (Yes/No), correct dose adjustments based on levels? (Yes/No) and prescription screened by a pharmacist? (Yes/No). Data was input into Microsoft Excel for analysis. The period covered was 01/12/2022 to 31/05/2023. Ethics approval was not required, as clinical audits do not require ethical review. The inclusion criterion was adult patients prescribed intravenous vancomycin. The exclusion criteria were patients in maternity, labour, and renal wards, due to different guidelines and ITU due to no EPMA. The population size was 243; sample size (n) =150 ensuring a 95% confidence level. Results In total, 150 patient drug charts were analysed, of which 96 % had their vancomycin indication documented. 65.3% of patients had the correct loading dose, 64.7% had the correct maintenance dose. 32.23% had the initial trough level done at the right time and 35% had correct subsequent trough levels measured. 44% had correct dose adjustments based on their trough levels and 57.33% had their prescriptions screened by a pharmacist. Discussion and conclusion None of the target compliance rates were met, highlighting significant issues with vancomycin dosing and therapeutic monitoring within the trust. Therapeutic drug monitoring (TDM) is crucial to ensure optimal patient outcomes2. Audit findings have been shared with the wider multidisciplinary team, education on TDM has taken place with junior pharmacists and digital prompts on EPMA have been included to help improve adherence. A limitation of this audit is its retrospective nature, useful for trend analysis but not for identifying causes. A prospective audit was not feasible due to staffing pressures. Conducting clinical audits are an important tool for assessing and ensuring safe clinical practice.

Detection of DNA of Leishmania infantum in the brains of dogs without neurological signs in an endemic region for leishmaniasis in the state of Rio Grande do Sul, Brazil.

Canine visceral leishmaniasis (CVL) is a parasitic disease caused by the protozoan Leishmania infantum. Neurological infection occurs due to the parasite's ability to cross the blood-brain barrier. It is known that dogs can remain infected with a subclinical infection for life, potentially acting as reservoirs for L. infantum when bitten by sandflies. In this context, the objective of this study was to evaluate the occurrence of Leishmania spp. in the brains of dogs from the metropolitan region of Rio Grande do Sul, Brazil, without a history of neurological disease but residing in an endemic area for L. infantum. A total of 200 samples, from 2022 to 2023, were evaluated using conventional Polymerase Chain Reaction (PCR) with the primers Leishmini-F GGKAGGGGCGTTCTGC and Leishmini-R STATWTTACACCAACCCC, aiming to amplify a product of 120 base pairs for Leishmania spp. To identify the species, a multiplex PCR was used, differentiating L. braziliensis (127bp), L. amazonensis (100bp), and L. infantum (60bp), with the molecular target being the conserved region of the kinetoplast DNA (kDNA) minicircle, specific to Leishmania spp. Of the 200 samples evaluated, 26.5% (53/200) tested positive in the conventional PCR reaction for Leishmania spp., with the PCR multiplex the only species detected was Leishmania infantum. The average age of the positive animals was 5.08years, with 47.2% being females and 52.8% being males; among these, mixed-breed dogs were the most predominant, representing 43.4% of the total. Clinical signs varied: hepatomegaly in two dogs, pronounced neutrophilic hepatitis in one, splenomegaly in one with lymphoid hyperplasia, and glomerulonephritis and nephritis in two animals. Mild anemia and thrombocytopenia were found in eight, with pale mucous membranes in three, and diffuse alveolar edema in one case. Notable pathological findings included suspected distemper in one animal and lymphoplasmacytic meningitis in another. Histopathological findings revealed alveolar edema and acute renal failure. A third dog exhibited bilateral hydrocephalus and diffuse edema in the brain. Additional changes, such as mild inflammatory infiltrate and slight vacuolar degeneration, were observed in 11.3% of the analyzed brains. There was no clinical suspicion of leishmaniasis in any of the studied cases. Therefore, the detection of L. infantum DNA in the brains of dogs suggests that animals with subclinical infection may play a crucial role in the spread of leishmaniasis, and infection by Leishmania spp. should be considered as a differential diagnosis for neurological disease in endemic areas for the protozoan.

The association between stress hyperglycemia ratio and clinical outcomes in patients with sepsis-associated acute kidney injury: a secondary analysis of the MIMIC-IV database

BackgroundThe stress hyperglycemia ratio (SHR) is associated with poor outcomes in critically ill patients. However, the relationship between SHR and mortality in patients with sepsis-associated acute kidney injury (SA-AKI) remains unclear.MethodsThe data of patients with SA-AKI, identified based on the KDIGO criteria, were retrospectively collected from the Beth Israel Deaconess Medical Center between 2008 and 2019. SHR was calculated as follows: (glycemia [mmol/L]) / (1.59 × HbA1c [%] – 2.59). Primary outcomes were 30-day and 1-year mortality. The cumulative incidence of all-cause mortality was assessed using Kaplan–Meier survival analysis. Multivariable-adjusted logistic and Cox models and restricted cubic spline curves were used to analyze the correlation between SHR and all-cause mortality. Post-hoc subgroup analysis was performed to compare the effects of SHR across different subgroups.Results1161 patients with SA-AKI were identified and categorized into four SHR quartiles as follows: Q1 (0.26, 0.90), Q2 (0.91, 1.08), Q3 (1.09, 1.30), and Q4 (1.31, 5.42). The median age of patients was 69 years, with 42.7% of the patients being women and 20.2% of the patients having chronic kidney disease. The 30-day and 1-year mortality were 22.1% and 35.0% respectively. Kaplan–Meier survival analysis indicated a gradual decrease in survival probability with increasing SHR quartiles. An increased SHR exhibited a strong correlation with 30-day mortality (hazard ratio [HR], 1.50; 95% confidence interval [CI], 1.18–1.90; P < 0.001) and 1-year mortality (HR, 1.32; 95% CI, 1.06–1.65; P = 0.014). SHR has a nonlinear relationship with 1-year mortality but not with 30-day mortality (P-nonlinear = 0.048 and 0.114, respectively). The results of subgroup analysis were mostly consistent with these findings.ConclusionAn increased SHR is independently associated with 30-day and 1-year mortality in patients with SA-AKI. Therefore, SHR may serve as an effective tool for risk stratification in patients with SA-AKI.

Inhibiting SIRT2 Attenuates Sepsis-Induced Acute Kidney Injury via FOXO1 Acetylation-Mediated Autophagy Activation

Abstract Sepsis-associated acute kidney injury (SAKI), a common complication in intensive care units (ICUs), is linked to high morbidity and mortality. Sirtuin 2 (SIRT2), an NAD+-dependent deacetylase, has been shown to have distinct effects on autophagy regulation compared to other sirtuins, but its role in SAKI remains unclear. This study explored the potential of SIRT2 as a therapeutic target for SAKI. We found that inhibition of SIRT2 with the antagonist AGK2 improved the survival of septic mice. SIRT2 inhibition reduced kidney injury, as indicated by lower levels of KIM-1, NGAL, serum creatinine (Scr), blood urea nitrogen (BUN), and proinflammatory cytokines following cecal ligation and puncture (CLP). Pretreatment with AGK2 in septic mice increased autophagosome and autolysosome formation in renal tubular epithelial cells (RTECs) and upregulated LC3 II expression in the renal cortex. Consistent with in vivo findings, SIRT2 gene silencing promoted autophagy in LPS-treated HK-2 cells, whereas SIRT2 overexpression inhibited it. Mechanistically, SIRT2 inhibition increased FOXO1 acetylation, inducing its nuclear-to-cytoplasmic translocation, which promoted kidney autophagy and alleviated SAKI. Our study suggests SIRT2 as a potential target for SAKI therapy.