Rutin loaded bilosomes for enhancing the oral activity and nephroprotective effects of rutin in potassium dichromate induced acute nephrotoxicity in rats.

Rutin, a flavone glycoside, has shown to have a significant beneficial kidney protection effect in drug-induced nephropathy. However, its poor solubility and low oral bioavailability have limited its pharmacological applications. This study aimed at formulating rutin-loaded bilosomes to enhance the renal protective effect of rutin for oral application. Rutin-loaded bilosomes were developed using thin-film hydration technique. The prepared formulations were characterized by entrapment efficiency percentage (EE%), vesicular size (VS) and zeta potential (ZP) measurement. The developed formula exhibited moderate EE%, ranging from 20.02 ± 2.85 to 48.57 ± 3.57%, suitable VS results that ranged from 502.1 ± 36 to 665.1 ± 45 nm and high ZP values (≤ -41.4 ± 7.27 mV). Transmission electron microscopy revealed the spherical shape of the developed bilosomes. The in-vitro release study revealed prolonged release of rutin from bilosomes, relative to free drug. F2, prepared using the molar ratio span 60: cholesterol: sodium cholate 1:1:0.5, was selected for further investigations as it showed the highest EE%, smallest VS, optimum ZP, and persistent release profile. In-vivo studies were performed on drug-induced nephropathy in rats. Acute renal failure was induced using a single dose of potassium dichromate (PDC; 15 mg/kg; i.p). The selected formulation, F2, alleviated kidney dysfunction, oxidative stress and inflammation via decreasing MDA, TNF-α and TGF-ß and increasing GSH. In addition, F2 promoted Akt/PI3K activation against PDC-induced acute renal failure. Histopathology results came in accordance with in-vivo results. Thus, bilosomes could be considered a potential delivery system for enhancing the oral delivery and kidney protection activity of rutin.

Bovine lactoferrin alleviates aflatoxin B1 induced hepatic and renal injury in broilers by mediating Nrf2 signaling pathway.

Aflatoxin B1 (AFB1) a mycotoxin found in chicken feed that possess a global hazard to poultry health. However different potent compounds like bovine lactoferrin (bLF) may prove to be protective effects against AFB1. This study aims to explore the protective effect of bLF against AFB1-induced injury in the liver and kidney in broiler. For this purpose, 600 broilers chicks were randomly alienated into 5 groups (n = 120 each): negative control; positive control (3 mg/kg AFB1), and bLF high, medium, and low dosage groups (600 mg/kg, 300 mg/kg, and 150 mg/kg, respectively). The results highlight that AFB1 toxicity in birds exhibited low feed intake, reduction in weight gain, and a decrease in FCR while, bLF regulated these adverse effects. Meanwhile, AFB1 group showed higher levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) and lower levels of superoxide dismutase (SOD) and glutathione (GSHpx) in liver, while urea and creatinine were decline in kidney. Supplementation with bLF effectively controlled these biomarkers and control the negative effects of toxicity. Furthermore, hematoxylin and eosin (H&E) staining exhibited normal morphological structures within liver and kidney in the bLF treated groups, while degenerative changes were observed in AFB1 group. Similarly, bLF, decreased oxidative stress and thus prevented apoptosis in the liver and kidney cells of the birds. Whereas, mRNA level of mitochondrial apoptosis related gene including Bcl-2 (Bak and Bax), caspase-3 and caspase-9 was upregulated, while bcl2 gene were downregulated in AFB1 group. Dietary supplementation of bLF effectively normalizes the expression of these genes. AFB1 exposed birds shown to decrease gene expression level of the crucial component of Nrf2 pathway, responsible to regulate antioxidant defense. Interestingly, bLF reverse these detrimental effects of and restore the normal expression levels of Nrf2 pathway. Conclusively, our findings demonstrate that bLF mitigates the detrimental effects of AFB1, besides regulation of the apoptosis-related genes via mitochondrial pathways. These findings validate that the bLF (600 mg/kg) could be used as protective agent against AFB1-induced liver and kidney damage.

Paraquat Toxicity Leading to Acute Kidney Injury: A Case Report in an Adult Patient.

ABSTRACT: Paraquat poisoning poses a significant and emerging public health challenge in developing countries. The distribution and usage of Paraquat, a potent herbicide, remain unrestricted in many regions despite its high fatality rate and absence of a specific antidote. Paraquat mostly involves lungs but can also involve the kidneys and liver. Diagnostic challenges and a lack of available samples at presentation contribute to underreporting and limited awareness among healthcare providers, making paraquat poisoning a neglected toxicological emergency. Herein, we present a case of a 40-year-old male who presented to the emergency department on the fourth day after ingesting paraquat in a suicidal attempt. Upon presentation, he had erosion on the tongue and posterior pharyngeal wall, along with deranged renal function tests and elevated serum creatinine levels. The patient developed acute kidney injury, with serum creatinine levels rapidly rising from normal to 3.85 mg/dl, accompanied by a decrease in daily urine output. He was managed conservatively, and his hospital stay was uneventful.

Mitigative role of cysteamine against unilateral renal reperfusion injury in Wistar rats.

Background: Ischemia-reperfusion injury (IRI) is unavoidable during kidney transplant and it is responsible for delayed or non-function after kidney transplantation. Cysteamine is the standard drug in the management of nephropathic cystinosis and its extra-renal complications. Thus, we designed this study to investigate its potential against renal reperfusion injury. Results: Significant elevation of H2O2, MDA, and nitrite and reduced GPx, GSH, and protein thiol in the Ischemia-reperfusion injury rats was reversed by cysteamine (50 and 100 mg/kg). Serum MPO, TNF-α, IL-1ß, creatinine, and AOPP were significantly elevated in IRI while rats treated with cysteamine revealed a significant decrease (p < 0.05) in the activities of these pro-inflammatory and renal injury markers. Conclusion: Based on its activity against inflammation, apoptosis, and free radical-induced stress, cysteamine has great potential to be used as a kidney transplant pre-operative drug to prevent renal reperfusion injury.

Risk factors associated with hospital mortality in non-surgical patients receiving extracorporeal membrane oxygenation and continuous renal replacement treatment: a retrospective analysis.

OBJECTIVES: The prognosis-predicting factors for non-surgical patients receiving continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) remains limited. In this study, we aim to analyze prognosis-predicting factors in the non-surgical patients receiving these two therapies. METHODS: We retrospectively analyzed data from non-surgical patients with ECMO treatment from December 2013 until April 2023. Hospital mortality was primary endpoint of this study. The area under the curve and receiver operating characteristic curves were used to assess the sensitivity and specificity of mortality. The independent risk factors were identified by multivariate logistic regression. The prediction model was a nomogram, and decision curve analysis and the calibration plot were used to assess it. Using restricted cubic spline curves and Spearman correlation, the correlation analysis was performed. RESULTS: The model that incorporated CRRT duration and age surpassed the two variables alone in predicting hospital mortality in non-surgical patients with ECMO therapy (AUC value = 0.868, 95% CI = 0.779-0.956). Older age, CRRT implantation, and duration were independent risk factors for hospital mortality (all p < 0.05). The nomogram predicting outcomes model containing on CRRT implantation and duration was developed, and the consistency between the predicted probability and observed probability and clinical utility of the models were good. CRRT duration was negatively associated with hemoglobin concentration and positively associated with urea nitrogen and serum creatinine levels. CONCLUSION: Hospital mortality in non-surgical ECMO patients was found to be independently associated with older age, longer CRRT duration, and CRRT implantation.

A comparison of the potential of melatonin and tryptophan to ameliorate CCl4-induced hepatic and renal toxicity in Wistar rats.

CCl4 causes oxidative injury, fatty degeneration, fibrosis of the liver, renal failure, and even hepatocellular and renal carcinoma. Certain substances have the potential to neutralize the harmful effects of CCl4, so it will lead to numerous beneficial effects. Melatonin (MEL) is a powerful antioxidant that regulates circadian rhythm and has beneficial effects on organism; tryptophan (TRP) is its precursor necessary for the synthesis of MEL. The aim of the current study was to determine whether MEL and TRP, have protective effects during subchronic application of CCl4 to the liver and kidneys. Results suggest that CCl4 led to decrease of total proteins, albumins, globulins, erythrocytes, hemoglobin, and hematocrit; and increase of creatinine, AST, ALT values, and leukocytes. MEL and TRP both showing protective effects on regulation of serum proteins, albumins, globulins, A/G, AST, ALT, and creatinine levels. TRP had been shown to have potential in regulation of disbalanced hematological parameters caused by CCl4. TRP had beneficial effects on hepatocyte morphology in term of beaded chromatin and preserved cell morphology. Overall, oral supplementation of TRP had better protective effects on liver/kidneys compared to MEL.

The hepatorenal protective effects of silymarin in cancer patients receiving chemotherapy: a randomized, placebo-controlled trial.

BACKGROUND: Breast cancer is one of the most common diseases globally that may have side effects on liver and renal function. Pharmacological treatments to reduce adverse liver and renal effects are still limited. It has been proposed that silymarin may possess hepatoprotective and anti-inflammatory properties. The present trial aims to assess the hepatorenal protective efficacy of silymarin supplementation in cancer patients receiving chemotherapy in an outpatient setting. METHOD: This is a randomized, placebo-controlled clinical trial that recruited female breast cancer patients. Participants were randomly assigned to one placebo group and two intervention groups. The control group received 140 mg of placebo daily, while the two intervention groups received 140 mg silymarin daily. Follow-up assessments were conducted at baseline, 3 weeks, and 6 weeks. At the beginning of the study, the patients were subjected to a computed tomography (CT) scan, and the liver and renal parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, Blood urea nitrogen (BUN) and Creatinine (Cr) were examined through laboratory tests. RESULTS: Despite two deaths and three dropouts, 100 patients completed the study. Silymarin showed significant effects on liver enzymes in the levels of ALP and bilirubin (P < 0.05), with no significant impact on renal function in the levels of Blood urea nitrogen (BUN) and Creatinine (Cr) (P > 0.05). The medication was well-tolerated, with minimal reported side effects (P > 0.05). DISCUSSION: The study suggests that silymarin may have hepato-renal protective potential in breast cancer patients and improve patient tolerance to chemotherapy. The data presented on the efficacy and safety of silymarin may provide stronger foundation for further trials and for a possible use in clinical practice. TRIAL REGISTRATION INFORMATION: Registration Number: IRCT20201123049474N2, First Trial Registration: 16/08/2021, Access: https://www.irct.behdasht.gov.ir/trial/57641.

Metabolomics analysis reveals a protective effect of hydroxycitric acid on calcium oxalate-induced kidney injury.

Objectives: Prior research has indicated that hydroxycitric acid (HCA) can impede the formation of calcium oxalate (CaOx) crystals, yet the specific mechanisms underlying its therapeutic effects remain unclear. In this study, we delved into the protective effects of HCA against glyoxylate-induced renal stones in rats and sought to elucidate the underlying metabolic pathways. Materials and Methods: Forty rats were randomly assigned to five groups: control group, model group, L-HCA-treated group, M-HCA-treated group, and H-HCA-treated group. Von Kossa staining was conducted on renal sections, and blood urea nitrogen and serum creatinine were determined by biochemical analysis. Meanwhile, body weight and urine volume were also measured. We subjected urine samples from the rats to analysis using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Next, we employed a metabolomic approach to scrutinize the metabolic profiles of each group. Results: HCA significantly reduced blood urea nitrogen and serum creatinine, and increased body weight and urine volume. It also reduced CaOx crystal deposition. A total of 24 metabolites, exhibiting a significant reversal pattern following HCA administration, were identified as urine biomarkers indicative of HCA's preventive effects against CaOx crystal-induced renal injury. These metabolites are primarily associated with glycine, serine, and threonine metabolism; phenylalanine metabolism; tricarboxylic acid cycle; taurine and hypotaurine metabolism; and tryptophan metabolism. Conclusion: It was demonstrated that HCA has a protective effect against CaOx crystal-induced kidney injury in rats by modulating various metabolic pathways. Additionally, results suggest that HCA holds promise as a potential clinical therapeutic drug for both the prevention and treatment of renal stones.

Zero-Contrast Transcatheter Aortic Valve Implantation vs. Standard Practice: Periprocedural and Long-Term Clinical Outcomes.

Background: We aimed to compare the procedural efficacy and long-term clinical results of a totally contrast-free Transcatheter Aortic Valve Implantation (TAVI) procedure (i.e., contrast dye was not used for either the pre-procedural assessment or during the procedure) to those of standard practice in patients with severe renal dysfunction. Methods: All consecutive patients with a glomerular filtration rate (GFR) ≤ 35 mL/min and severe aortic stenosis who were treated with transfemoral TAVI at our Institution were included in the registry. The zero-contrast patients underwent carbon dioxide angiography and a non-contrast CT scan for assessment of vascular access suitability, and aortic annulus sizing was performed by a TEE, and the procedural guidance was fluoroscopic and echocardiographic. Procedural outcomes were evaluated, and clinical long-term follow-up was performed for all included patients. Results: A total of 44 patients (median age, 85 (IQR, 80.75-87.00)) were included in the zero-contrast group (TEE guidance and general anesthesia in 37 (84%) patients), while 63 patients were included in the standard practice arm (82 ± 78 mL of contrast dye used). Procedural success was obtained in 100% of cases. There were no differences in procedural outcomes, including final mean aortic gradients (5.5 (IQR, 5.0-10.0) mmHg in the zero-contrast group vs. 6.0 (IQR, 5.0-10.0) mmHg in the standard practice group) and rate of at least a moderate paravalvular leak (0% vs. 1.6% in the zero-contrast and standard practice groups, respectively; p = 0.31). No differences in AKI during the hospital stay were observed. Over a median follow-up of 3.3 years, there was a significantly lower rate of AKI (1.2% vs. 25.9%, p < 0.001) and rehospitalizations (1.6% vs. 35.5%, p < 0.00) in standard practice group. Conclusions: We showed for the first time the feasibility and efficacy of a totally contrast-free strategy compared to standard practice in TAVI patients with severe renal dysfunction. Besides achieving comparable procedural results, the zero-contrast strategy showed a better long-term clinical outcome in reducing hospital readmissions for kidney function deterioration.

Renal protective and immunoregulatory effects of Lactobacillus casei strain Shirota in nephropathy-prone mice.

Introduction: The incidence of severe acute kidney injury (AKI) is considerably high worldwide. A previous study showed that gut microbial dysbiosis was a hallmark of AKI in mice. Whether the probiotic Lactobacillus casei strain Shirota (LcS) plays a role in kidney disease, particularly AKI, remains unclear. Methods: To investigate the effects of LcS on kidney injury, tubule-specific conditional von Hippel-Lindau gene-knockout C57BL/6 mice (Vhlhdel/del mice) were supplemented without (Ctrl) or with probiotics (LcS) in Experiment 1, and their lifespan was monitored. Additionally, the Vhlhdel/+ mice were supplemented without (Ctrl and AA) or with probiotics (LcS and LcS + AA) in Experiment 2. Probiotic LcS (1 × 109 colony-forming units) was supplemented once daily. After 4 weeks of LcS supplementation, AA and LcS + AA mice were administered aristolochic acid (AA; 4 mg/kg body weight/day)-containing purified diet for 2 weeks to induce AA nephropathy before sacrifice. Results: Supplementation of LcS significantly prolonged the lifespan of Vhlhdel/del mice, suggesting a potential renal protective effect. AA induced-nephropathy increased not only the indicators of renal dysfunction and injury, including urinary protein and kidney injury molecule (KIM)-1, serum blood urea nitrogen (BUN) and creatinine, but also serum interleukin (IL)-6 levels, renal macrophage infiltrations, and pathological lesions in Vhlhdel/+ mice. LcS supplementation significantly reduced urinary protein and KIM-1 levels, serum BUN and IL-6 levels, and renal M1 macrophages, tissue lesions, and injury scores. We also found that LcS maintained gut integrity under AA induction and increased intestinal lamina propria dendritic cells. Furthermore, LcS significantly reduced pro-inflammatory IL-17A and upregulated anti-inflammatory IL-10 production by immune cells from intestinal Peyer's patches (PP) or mesenteric lymph nodes (MLN), and significantly increased IL-10 and reduced IL-6 production by splenocytes. Conclusion: Prior supplementation with probiotic LcS significantly alleviated the severity of renal injury. This renal protective effect was partially associated with the enhancements of intestinal and systemic anti-inflammatory immune responses, suggesting that LcS-induced immunoregulation might contribute to its renal protective effects.

CO2 Angiography in the Standard and Complex Endovascular Repair of the Abdominal Aorta-A Narrative Review of the Literature.

Background/Objectives: Carbon dioxide digital-subtraction angiography (CO2-DSA) is an increasingly adopted technique in endovascular aortic repair (EVAR) and fenestrated/branched EVAR (F/B-EVAR); it is used to reduce the amount of iodinate contrast medium (ICM) and prevent postoperative renal function worsening (PO-RFW). Our aim is to report results from the literature on EVAR and F/B-EVAR procedures using CO2-DSA, together with wider applications in aortic endovascular treatment. Methods: We performed a literature review by searching electronic databases for published data on CO2-DSA during EVAR and F/B-EVAR procedures. The endpoints were postoperative renal function worsening (PO-RFW) and efficacy of intraoperative arterial visualization. Further, applications of CO2 for thoracic endovascular aortic repair (TEVAR) were described. Results: Seventeen studies reporting results on CO2-DSA in EVAR (644 patients) were retrieved. Overall, 372 (58%) procedures were performed with CO2 alone, and 272 (42%) were performed with CO2+ICM. Eight studies analyzed the effect of CO2-DSA angiography on PO-RFW; four studies showed a significantly lower rate of PO-RFW compared to ICM. Five studies (153 patients) analyzed intraoperative arterial visualization with CO2-DSA; renal and hypogastric arteries were effectively visualized in 69% and 99% of cases, respectively. The use of CO2-DSA in F/B-EVAR has not been widely investigated. The largest series reported that PO-RFW was lower in the CO2 vs. ICM group. Conclusions: Carbon dioxide is widely applied in modern aortic endovascular treatment. CO2-DSA for EVAR and F/B-EVAR is an efficient technique for reducing PO-RFW while allowing acceptable arterial intraoperative visualization.

Characterization and Clinical Significance of Hemolysis After Pulsed Field Ablation for Atrial Fibrillation: Results of a Multicenter Analysis.

BACKGROUND: Pulsed field ablation (PFA) is increasingly used in clinical practice for the treatment of atrial fibrillation. While the susceptibility of erythrocytes to electroporation is well established, the effect of cardiac PFA technologies on hemolysis has remained underreported. The aim of this study was to investigate the incidence, severity, and clinical impact of PFA-induced hemolysis. METHODS: We included n=145 patients undergoing atrial fibrillation catheter ablation with a pentaspline PFA catheter (biphasic, bipolar pulses of 2 kV) and n=70 patients receiving radiofrequency ablation (40-90 W) at 4 high-volume European centers. The lesion set comprised pulmonary vein isolation for paroxysmal atrial fibrillation and pulmonary vein isolation±additional lesions for persistent atrial fibrillation. Hemolysis and renal function biomarkers were analyzed in blood samples at baseline, at the end of ablation, and 24 hours after the procedure. RESULTS: Baseline characteristics were well balanced between groups (overall mean, 65.7±9.4 years; 69.3% male). The ablation procedures comprised a mean of 61.6±27.4 PFA deliveries and 26.3±15.0 minute RF duration. Hemolysis was detected in 94.3% versus 6.8% of patients after PFA versus radiofrequency ablation (P<0.001): PFA was associated with significantly lower haptoglobin levels (0.5±0.4 versus 1.0±0.4 g/L), while free plasma hemoglobin (592.8±330.6 versus 147.8±183.0 mg/L), bilirubin (21.3±11.3 versus 14.8±8.8 µmol/L), and LDH (lactate dehydrogenase, 352.7±115.7 versus 253.2±56.5 U/L) were significantly higher after PFA versus radiofrequency ablation (all P<0.001). Hemolysis correlated with the number of PFA deliveries (r=0.62 [95% CI, 0.33-0.80]; P<0.001), with the highest severity occurring ≥54 PFA deliveries. After PFA, hemoglobinuria occurred in 36.4%, while creatinine increase was higher in patients with baseline glomerular filtration rate <50 mL/min versus baseline glomerular filtration rate >50 mL/min (Δcrea, 27.0±103.1 versus -0.2±12.1 µmol/L; P=0.010). CONCLUSIONS: Intravascular hemolysis is a frequent finding after PFA and increases with the number of PFA deliveries. Until the clinical impact of PFA-associated hemolysis is fully elucidated, a careful titration of PFA deliveries during the ablation procedure is warranted.

The Value of Bedside Ultrasound Evaluation of Intravenous Ultrasound Grading System Combined with TyG Index in Predicting Acute Renal Injury in Patients with Acute Hyperlipidemic Pancreatitis.

Aims/Background Bedside ultrasound evaluation of venous excess ultrasound (VExUS) combined with the triglyceride-glucose (TyG) index plays an important role in predicting acute kidney injury (AKI) in patients with acute hyperlipidemic pancreatitis. VExUS can effectively evaluate the degree of venous congestion, while the TyG index is valuable in predicting severe pancreatitis. The combination of these two methods is expected to provide a more accurate AKI risk assessment tool for clinical practice. This study explores the value of combining bedside ultrasound evaluation using the VExUS grading system with the TyG index in predicting acute renal damage in patients with acute hyperlipidemic pancreatitis. Methods From January 2021 to December 2023, 110 patients with acute hyperlipidemic pancreatitis were selected. The patients were divided into two groups based on whether they were complicated with acute kidney injury (AKI): the AKI group (n = 23) and the non-AKI group (n = 87). The general data of the two groups were compared, and the risk factors for AKI in patients with acute hyperlipidemic pancreatitis were analyzed using multivariate logistic regression. The predictive value was assessed using receiver operating characteristic curve (ROC) analysis. Results There were no statistically significant differences in age, gender, outcome, triglyceride (TG), total cholesterol, low-density lipoprotein (LDL) levels at admission, blood nutrition at discharge, creatinine (CREA) at discharge, underlying diseases, start time of enteral nutrition, complications, length of stay, Intensive Care Unit (ICU) days, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, blood glucose level, blood amylase level, CREA, blood urine nitrogen (BUN), blood purification treatment (p > 0.05). However, there were significant differences (p < 0.05) between the TyG index and the VExUS score, with variables including the TyG index and the VExUS score (included in the logistic regression analysis as variables), and AKI (AKI = 1, non-AKI = 0) as dependent variables. Multiple logistic regression results showed that the TyG index and VExUS score were independent predictors of AKI in patients with acute hyperlipidemia pancreatitis (p < 0.05). The standard error, sensitivity and specificity of the TyG index, VExUS score and combined model for predicting AKI in these patients were 0.064, 73.91 and 87.45; 0.036, 78.16 and 95.65; 0.010, 100.00 and 95.65, respectively (p < 0.05). Conclusion The VExUS score combined with the TyG index is highly valuable in predicting AKI in patients with acute hyperlipidemic pancreatitis.

Renal angioembolization vs. surgery for high-grade renal trauma: a nationwide comparative analysis.

PURPOSE: Renal angioembolization (RAE) is widely employed in low-grade renal injuries and associated with improved patient outcomes, while surgery remains the mainstay for managing high-grade injuries. We compared the outcomes following surgery and RAE in high-grade renal trauma (HGRT). METHODS: We used the ACS TQIP 2016-2020 to identify patients ≥ 16 years with HGRT who underwent RAE or surgery. Morbidity was the primary outcome, while mortality and lengths of stay were secondary outcomes. We accounted for clinically relevant characteristics using multilevel logistic regression analyses. RESULTS: We included 591 patients, of whom 279 (47.2%) underwent RAE. After adjusting, there was no difference in morbidity, hospital LOS, or ICU LOS. The surgery cohort had increased odds of mortality (aOR 4.93; [95% CI] 1.53-15.82; p = 0.007) compared to RAE. In the penetrating injury subgroup, no associations between management and outcomes were observed. In the grade V injury subgroup, morbidity was significantly higher after surgery (aOR 4.64; [95% CI] 1.49-14.47; p = 0.008). CONCLUSION: Overall, RAE did not significantly impact morbidity but was associated with improved mortality. RAE could safeguard renal function by augmenting the efficacy of concurrent non-operative interventions. Randomized studies are needed to further validate the utility of RAE in HGRT.

Endoplasmic reticulum stress promotes oxidative stress, inflammation, and apoptosis: A novel mechanism of citrinin-induced renal injury and dysfunction.

Citrinin (CTN) has been reported to induce renal failure and structural damage, but its nephrotoxic effects and mechanisms are not fully understood. Therefore, we established a model by orally administering CTN (0, 1.25, 5, or 20 mg/kg) to mice for 21 consecutive days. Histological and biochemical analyses revealed that CTN caused structural damage to renal tubules, increased inflammatory cell infiltration, and elevated levels of serum markers of renal function (creatinine, urea, and uric acid). Moreover, mRNA transcript levels of the inflammatory factors TNF-α, IL-1ß, and IL-6 were increased, indicating the occurrence of an inflammatory response. Furthermore, exposure to CTN induced renal oxidative stress by decreasing antioxidant GSH levels, antioxidant enzyme (SOD, CAT) activities, and increasing oxidative products (ROS, MDA). In addition, CTN increased the expression of proteins associated with endoplasmic reticulum (ER)stress and apoptotic pathways. ER stress has been shown to be involved in regulating various models of kidney disease, but its role in CTN-induced renal injury has not been reported. We found that pretreatment with the ER stress inhibitor 4-PBA (240 mg/kg, ip) alleviated CTN-induced oxidative stress, NF-κB pathway mediated inflammatory response, and apoptosis. Interestingly, 4-PBA also partially alleviated renal structural damage and dysfunction. Thus, ER stress may be a novel target for the prevention and treatment of CTN-induced renal injury.

Bisphenol P induces increased oxidative stress in renal tissues of C57BL/6 mice and human renal cortical proximal tubular epithelial cells, resulting in kidney injury.

Bisphenol P (BPP) has been detected in human biological samples; however studies on its nephrotoxicity are scarce. Given the susceptibility of kidneys to endocrine-disrupting chemicals, there is an urgent need to investigate the renal toxicity of BPP. This study aimed to evaluate the effects of different concentrations of BPPs on the kidneys of C57BL/6 mice and elucidate the underlying mechanisms of renal damage using a combination of mouse renal transcriptomic data and human renal proximal tubular epithelial cells (HK-2). Mice were exposed to BPP (0, 0.3, 30, 3000 µg/kg bw/d) via gavage for 5 weeks. Renal injury was assessed based on changes in body and kidney weights, serum renal function indices, and histopathological examination. Transcriptomic analysis identified differentially expressed genes and pathways, whereas cellular assays were used to measure cell viability, reactive oxygen species (ROS), apoptosis, and the expression of key genes and proteins. The results show that BPP exposure induces renal injury, as evidenced by increased body weight, abnormal renal function indices, and renal tissue damage. Transcriptomic analysis revealed alterations in genes and pathways related to oxidative stress, p53 signaling, autophagy, and apoptosis. Cellular experiments confirmed that BPP induces oxidative stress and apoptosis. Furthermore, BPP exposure significantly inhibits autophagy, potentially exacerbating apoptosis and contributing to kidney injury. Treatment with a ROS inhibitor (N-Acetylcysteine, NAC) mitigated BPP-induced autophagy inhibition and apoptosis, implicating oxidative stress as a key factor. BPP exposure may lead to renal injury through excessive ROS accumulation, oxidative stress, inflammatory responses, autophagy inhibition, and increased apoptosis. The effects of NAC highlight the role of oxidative stress in BPP-induced nephrotoxicity. These findings enhance our understanding of BPP-induced nephrotoxicity and underscore the need to control BPP exposure to prevent renal disease. This study emphasized the importance of evaluating the safety of new Bisphenol A analogs, including BPP, in environmental toxicology.

Risk factors for mortality in patients receiving extracorporeal membrane oxygenation.

OBJECTIVE: Patients on extracorporeal membrane oxygenation (ECMO) are often complex and have a high mortality rate. Currently, risk assessment and treatment decisions for patients receiving ECMO are controversial. Therefore, we sought to identify risk factors for mortality in patients receiving ECMO and provide a reference for patient management. METHODS: We retrospectively analyzed the clinical data of 199 patients who received ECMO support from December 2013 to April 2023. Univariate and multivariable logistic regression analyses were used to identify risk factors. The cutoff value was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 199 patients were selected for this study, and the mortality rate was 76.38%. More than half of the patients underwent surgery during hospitalization. Multivariable logistic regression analysis revealed that continuous renal replacement therapy (CRRT) implantation (OR = 2.994; 95% CI, 1.405-6.167; p = 0.004) and age (OR = 1.021; 95% CI, 1.002-1.040; p = 0.032) were the independent risk factors for mortality. In the ROC curve analysis, age had the best predictive effect (AUC 0.646, 95% CI 0.559-0.732, p = 0.003) for death when the cutoff value was 48.5 years. Furthermore, in patients receiving combined CRRT and ECMO, lack of congenital heart disease and previous surgical history were the independent risk factors for mortality. CONCLUSIONS: CRRT implantation and age were independent risk factors for patients with ECMO implantation in a predominantly surgical cohort. In patients receiving a combination of CRRT and ECMO, lack of congenital heart disease and previous surgical history were independent risk factors for mortality.

Protective effect of ß-sitosterol against high-fructose diet-induced oxidative stress, and hepatorenal derangements in growing female sprague-dawley rats.

BACKGROUND: Chronic consumption of a high-fructose diet causes oxidative stress that compromises kidney and liver health. ß-sitosterol (Bst), a phytosterol, is a functional nutrient with health benefits. ß-sitosterol antioxidant activity protects the liver and kidney from ROS-mediated damage and lipid peroxidation. We evaluated the potential renoprotective and hepatoprotective effects of orally administrated ß-sitosterol in high-fructose diet-fed growing female rats. Thirty-five 21-day old female Sprague-Dawley rat pups were randomly assigned to and administered the following treatments for 12 weeks: group I- standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II- SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III- SRC + FS + 100 mg/kg body mass (BM) fenofibrate in gelatine cube; group IV- SRC + FS + 20 mg/kg BM ß-sitosterol gelatine cube (Bst) and group V- SRC + PW + Bst. The rats were fasted overnight, weighed then euthanised. Blood was collected, centrifuged and plasma harvested. Livers and kidneys were excised, weighed and samples preserved for histological assessments. Plasma biomarkers of oxidative stress, liver and kidney function and renal tubular injury were assessed. RESULTS: High fructose diet fed rats had increased plasma KIM-1, NGAL (p < 0.001) and MDA levels (p < 0.05). Dietary fructose caused microvesicular and macrovesicular steatosis, and reduced glomerular density, Bowman's capsule area and urinary space. ß-sitosterol protected against the high-fructose diet-induced hepatic steatosis and glomerular disturbances without adverse effects on liver and kidney function. CONCLUSIONS: ß-sitosterol, as a dietary supplement, could potentially be exploited to prevent high-fructose diet-induced NAFLD and to protect against high-fructose diet-induced renal tubular injury.

Alterations in the gut microbiome and metabolism profiles reveal the possible molecular mechanism of renal injury induced by hyperuricemia in a mouse model of renal insufficiency.

Objectives: To investigate the role of the intestinal flora and metabolites in the development of hyperuricemic renal injury in chronic kidney disease (CKD).Methods: Unilaterally nephrectomized mice were fed with adenine and potassium oxonate for 9 weeks. HE staining combined with plasma biochemical indicators was used to evaluate renal pathological and functional changes. We conducted 16S rRNA sequencing and untargeted metabolomics on feces and plasma samples to reveale changes in intestinal microbiota and metabolites.Result: Our analysis revealed significant differences in 15 bacterial genera, with 7 being upregulated and 8 being downregulated. Furthermore, metabolomic analysis revealed changes in the distribution of amino acid and biotin metabolites in basic metabolic pathways in both feces and serum. Specifically, differentially abundant metabolites in feces were associated primarily with histidine metabolism; the biosynthesis of phenylalanine, tyrosine, and tryptophan; and tyrosine metabolism. In plasma, the differentially abundant metabolites were involved in multiple metabolic pathways, including aminoacyl-tRNA biosynthesis; glycine, serine, and threonine amino acid metabolism; valine, leucine, and isoleucine biosynthesis; tyrosine biosynthesis and metabolism; biotin metabolism; and taurine and hypotaurine metabolism. Furthermore, correlation analysis revealed that Akkermansia, UCG-005, Lachnospiraceae_NK4A136_group, Lactococcus, and Butymonas were associated with various differentially abundant metabolites as well as renal function, oxidative stress, and mitophagy. The changes in the intestinal flora observed in hyperuricemia may lead to imbalances in amino acid and biotin metabolism in both the intestine and host, ultimately affecting oxidative stress and mitophagy in mice and accelerating the progression of CKD.Conclusion: Our findings provide insights into a potential pathogenic mechanism by which hyperuricemia exacerbates renal injury in mice with renal insufficiency. Understanding these pathways may offer new therapeutic strategies for managing hyperuricemic renal injury in CKD patients.

Unraveling Complexities: Rhabdomyolysis, Acute Renal Injury, and Compartment Syndrome Following a Wasp's Sting.

This study delves into the rare occurrence of rhabdomyolysis induced by wasp stings, emphasizing its toxic systemic repercussions. Drawing parallels with documented instances of insect bites worldwide, including those by honey bees and Africanized bees, the research explores the correlation between multiple wasp stings and acute renal failure associated with rhabdomyolysis. The venom's active components, such as amines, kinins, and histamine-releasing peptides, underpin toxic systemic reactions, leading to hemolysis, coagulopathy, and severe cytotoxicity-induced acute renal failure. Noteworthy is the emergence of blackish necroses at the sting site, suggesting intense cytotoxicity. The study also highlights skin necrosis as a prognostic indicator for toxic systemic reactions. The presented case manifests an anaphylaxis-like reaction, revealing insights into toxic responses devoid of IgE-mediated allergic reactions. Timely intervention, encompassing hydration, transfusion, and dialytic support, proves imperative in scenarios involving multiple wasp stings, offering successful outcomes documented through plasma exchange in severe cases. This research prompts considerations beyond anaphylaxis, urging exploration of severe toxic systemic reactions in the context of multiple wasp stings.