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[Display omitted] Acute kidney injury (AKI) is characterized by rapid and significant deterioration of renal function over a short duration with high mortality. However, the intricate pathophysiological mechanisms underlying AKI have hindered the development of effective therapeutic strategies. Recent research has highlighted the crucial role of ferroptosis in the pathogenesis of AKI and has identified it as a promising therapeutic target. Herein, we investigated the prophylactic efficacy of fullerenol nanoparticles, renowned for their broad-spectrum free radical scavenging capabilities and favorable biocompatibility, in preventing and mitigating ferroptosis-mediated cisplatin-induced AKI. Our findings demonstrate the remarkable potential of fullerenols in mitigating AKI. Specifically, fullerenols exert their protective effects primarily by suppressing renal lipid peroxidation and ferrous iron accumulation, which are two defining hallmarks of ferroptosis. Notably, fullerenols significantly inhibited the upregulation of key enzymes involved in the intracellular lipid peroxidation induced by cisplatin, including acyl-coA synthetase long chain family member 4 (ACSL4), arachidonate lipoxygenase 3 (ALOXE3), and cytochrome P450 oxidoreductase (POR), and enhanced antioxidant systems xc-/Glutathione (GSH)/Glutathione Peroxidase 4 (GPX4). Fullerenols also significantly suppressed the increase in mRNA expression of iron regulation-related genes and prevented the elevation of low-valent iron levels in the kidney tissue of AKI mice. Collectively, our study presents fullerenol as a promising drug candidate for the prevention of AKI in clinical settings, and provides valuable insights into the management of various ferroptosis-associated diseases. [ABSTRACT FROM AUTHOR]

BackgroundMethodsResultsConclusionPrevious studies have demonstrated that double-negative (DN) αβ T cells play an important role in immune responses during ischemic acute kidney injury (AKI). Here, we investigate the role of γ-chain cytokines in driving DN T cell proliferation in steady state and AKI, focusing on IL-2, IL-7, and IL-15.We assessed DN T cell proliferation in vitro in response to IL-2, IL-7, and IL-15, with co-culture experiments using renal tubular epithelial cells (RTECs) and IL-7 blockade. In vivo, wild-type and IL-7r knockout mice were studied to evaluate the impact of IL-7 on DN T cell expansion and kidney function during AKI. Human RTECs confirmed the relevance of these findings.All three cytokines promoted DN T cell proliferation in vitro, with IL-7 inducing the most robust expansion. Co-culture experiments showed RTECs as a key IL-7 source, and blockade reduced DN T cell expansion. In vivo, IL-7 complexes administered to wild-type mice increased DN T cells and selectively expanded the PD-1+ subset. IL-7 deficiency worsened renal outcomes during AKI. Human RTECs activated peripheral human DN T cells in vitro.These results establish IL-7 as pivotal for DN T cell expansion and highlight RTECs’ role in DN T cell homeostasis. [ABSTRACT FROM AUTHOR]

Background: While the cardiovascular risk of hyperglycemia has been thoroughly elucidated in patients with type 2 diabetes (T2DM) hospitalized for myocardial infarction, the evidence surrounding acute severe hyperglycemia is less well-established. Our study aimed to explore the impact of diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS), both severe hyperglycemic conditions, on cardiovascular outcomes in patients with T2D admitted for ST-elevation myocardial infarction (STEMI). Methods: We used the National Readmission Database (2016–2019) to extract patients with T2DM and STEMI at baseline. Subsequently, we selected cases of DKA and HHS. The primary endpoint was in-hospital mortality. Secondary endpoints included in-hospital acute renal failure, cardiogenic shock, and 30-day readmission and mortality. Results: The presence of DKA increased the adjusted odds of mortality and cardiogenic shock by almost 2-fold (adjusted Odds Ratios aOR = 2.30 [1.70–3.12], 2.055 [1.602–2.637], respectively) and renal failure by nearly 5-fold (aOR = 5.175 [4.090–6.546]). HHS was also associated with higher odds of mortality, acute renal failure, and cardiogenic shock. In 30 days, DKA and HHS increased the risk of readmission (aOR = 1.815 [1.449–2.75], 1.751 [1.376–2.228], respectively). There were no differences in the rates of cardiovascular disease, mortality, or other cardiovascular events between DKA and HHS patients. Within 30 days of readmission, DKA and HHS were associated with higher odds of readmission but not mortality. Cardiovascular disease was the most common etiology of readmission in all patients. The incidence of non-STEMI was the highest in DKA patients, and the incidence of STEMI was the highest in the HHS group. Conclusion: The presence of diabetic ketoacidosis or hyperglycemic hyperosmolar state is associated with higher odds of mortality, renal failure, cardiogenic shock, and 30-day readmission in STEMI patients with type 2 diabetes, highlighting the need for enhanced clinical management and monitoring of patients experiencing acute hyperglycemia. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) affects nearly half of children with severe malaria and increases the risk of adverse outcomes such as death and poor cognitive function. The pathogenesis and predictors of malaria-associated acute kidney injury (MAKI) are not fully described. This study aims to determine the clinical, immune, and genetic correlates of risk to AKI in Zambian children admitted with malaria. In addition, we intend to assess a modified renal angina index (mRAI), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and soluble urokinase receptor (suPAR), when done on the first day of admission, for the ability to predict AKI two days later (day 3) in children admitted with malaria. Methods: This is an unmatched case-control study with a nested prospective observational study. A case-to-control ratio of 1:1 is used and 380 children with malaria and aged less than 16 years are being recruited from two hospitals in Zambia. Eligible children are recruited after obtaining written informed consent. Recruitment occurs during the malaria season and began on 6th March 2024 and will continue until July 2025. AKI is defined using the 2012 KIDGO AKI creatinine criteria, and cases are defined as children admitted with malaria who develop AKI within 72 hours of admission, while controls are children admitted with malaria but with no AKI. Serum creatinine is collected on Day 1 within 24 hours of admission, on Day 3 and then again on discharge or day 7, whichever comes sooner. Baseline biomarker concentrations will be determined using the Luminex multiplex Elisa system or high-sensitivity ELISA. SPSS version 29 will be used for data analysis. Descriptive statistics and inferential statistical tests will be run as appropriate. A p ≤ 0.05 will be considered as significant. The sensitivity, specificity, and estimates of the area under the curve (AUC) for the renal angina score will be determined. [ABSTRACT FROM AUTHOR]

Background: Various treatments have been employed in managing type B aortic dissection (TBAD), encompassing open surgical repair (OSR), thoracic endovascular aortic repair (TEVAR), and optimal medical therapy (OMT). Nonetheless, the determination of the most efficacious treatment protocol remains a subject of debate. We aim to compare the treatments in patients with acute and subacute TBAD using a meta-analytic approach. Methods: A systematic search was conducted across databases including PubMed, EmBase, and the Cochrane Library for relevant studies published from their inception up to September 2024. Studies comparing OSR, TEVAR, and OMT for TBAD through controlled or direct comparative designs were incorporated. Pairwise comparison meta-analyses were performed employing odds ratios (OR) alongside 95% confidence intervals (CIs) to quantify intervention effects by using the random-effects model. Results: Thirty-one studies involving 34,681 patients with TBAD were included in the final meta-analysis. We noted OSR were associated with an increased risk of in-hospital mortality (OR: 2.41; 95%CI: 1.67–3.49; P < 0.001), paraplegia (OR: 3.60; 95%CI: 2.20–5.89; P < 0.001), limb ischemia (OR: 7.80; 95%CI: 2.39–25.49; P = 0.001) and bleeding (OR: 9.54; 95%CI: 6.57–13.85; P < 0.001) as compared with OMT. Moreover, OSR versus TEVAR showed an increased risk of in-hospital mortality (OR: 2.67; 95%CI: 1.92–3.72; P < 0.001), acute renal failure (OR: 1.98; 95%CI: 1.61–2.42; P < 0.001), myocardial infaraction (OR: 2.76; 95%CI: 1.64–4.65; P < 0.001), respiratory failure (OR: 2.19; 95%CI: 1.73–2.76; P < 0.001), or bleeding (OR: 1.88; 95%CI: 1.33–2.67; P < 0.001), and lower risk of reintervention (OR: 0.30; 95%CI: 0.10–0.89; P = 0.030). Finally, TEVAR was associated with an increased risk of stroke (OR: 1.77; 95%CI: 1.41–2.21; P < 0.001), limb ischemia (OR: 13.00; 95%CI: 4.33–39.06; P < 0.001), and bleeding (OR: 3.65; 95%CI: 2.40–5.55; P < 0.001) as compared with OMT. Conclusions: This study systematically compared various treatments and showed their safety and efficacy for acute and subacute TBAD. The results require further large-scale randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: The triglyceride–glucose (TyG) index is increasingly recognized for its ability to predict cardiovascular and metabolic risks. This study investigated the correlation between the TyG index and the risk of acute kidney injury(AKI) in critical ill patients with acute pancreatitis(AP). Methods: The Medical Information Mart for Intensive Care IV database was retrospectively searched to identify AP patients hospitalized in the intensive care unit. The primary outcome measure was the incidence of AKI. The secondary endpoint was in-hospital mortality and the rate of renal replacement therapy(RRT) use. Cox regression analysis and restricted cubic spline were used to analyze TyG index association with AKI risk. Kaplan–Meier survival analysis was performed to assess the incidence of endpoints in the different groups. Results: A total of 848 patients were enrolled. The incidence of AKI was 61.56%.The in-hospital mortality was 11.69%. Kaplan–Meier analysis showed that the TyG index ≥ 8.78 group has a high incidence of AKI and high risk of requiring RRT (P < 0.001). Multivariable Cox regression analysis showed whether TyG index was a continuous variable (HR, 1.65 [95% CI 1.10–2.48], P = 0.015) or a categorical variable (HR, 1.72 [95% CI 1.09–2.79], P = 0.028), and the TyG index was independently associated with the risk of AKI in AP patients. The restricted cubic splines model illustrated the linear relationship between higher TyG index and increased risk of AKI in this specific patient population. Conclusions: High TyG index is an independent risk factor for AKI in critical ill patients with AP. Assessing the TyG index may be beneficial for early stratification and interventions to improve prognosis. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury after CRS + HIPEC is a serious postoperative complication, but only a few studies have reported its postoperative risk factors. In addition, there are large discrepancies in the results of available observational studies. Methods: We searched The Cochrane Library, Embase, Web of Science,and PubMed to identify observational studies reporting risk factors for AKI after CRS + HIPEC. A meta-analysis was performed to investigate the effect of various preoperative and intraoperative risk factors on AKI after CRS + HIPEC. Results: A total of 7 studies were included in this study, comprising 1550 patients who developed AKI after CRS + HIPEC. The results of meta-analysis showed that the significant preoperative risk factors were age, sex, BMI, eGFR, Hb, PCI, diabetes mellitus, and hypertension. IO cisplatin, IO SBP < 100 was identified as an intraoperative risk factor, whereas IO mitomycin emerged as a protective factor for postoperative AKI. In addition, the risk of postoperative AKI varied by primary tumor site, with Appendix being less prone to AKI, while mesothelioma and ovarian, two sites with a greatly elevated risk of postoperative AKI. Conclusions: This meta-analysis identified a number of risk factors for postoperative AKI after CRS + HIPEC. By identifying these risk factors, it is more beneficial for clinicians to perform early preoperative interventions and select the most appropriate treatment strategy for their patients, thus minimizing the risk of postoperative AKI. Trial registration: PROSPERO CRD42024585269. [ABSTRACT FROM AUTHOR]

Ischemic acute kidney injury (AKI) is common in hospitalized patients and increases the risk for chronic kidney disease (CKD). Impaired endothelial cell (EC) functions are thought to contribute in AKI to CKD transition, but the underlying mechanisms remain unclear. Here, we identify a critical role for endothelial oxygen sensing prolyl hydroxylase domain (PHD) enzymes 1-3 in regulating postischemic kidney repair. In renal endothelium, we observed compartment-specific differences in the expression of the 3 PHD isoforms in both mice and humans. Postischemic concurrent inactivation of endothelial PHD1, PHD2, and PHD3 but not PHD2 alone promoted maladaptive kidney repair characterized by exacerbated tissue injury, fibrosis, and inflammation. scRNA-Seq analysis of the postischemic endothelial PHD1, PHD2, and PHD3-deficient (PHDTiEC) kidney revealed an endothelial hypoxia and glycolysis-related gene signature, also observed in human kidneys with severe AKI. This metabolic program was coupled to upregulation of the SLC16A3 gene encoding the lactate exporter monocarboxylate transporter 4 (MCT4). Strikingly, treatment with the MCT4 inhibitor syrosingopine restored adaptive kidney repair in PHDTiEC mice. Mechanistically, MCT4 inhibition suppressed proinflammatory EC activation, reducing monocyte-EC interaction. Our findings suggest avenues for halting AKI to CKD transition based on selectively targeting the endothelial hypoxia-driven glycolysis/MCT4 axis. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common critical clinical disease that is linked to significant morbidity, recurrence, and mortality. It is characterized by a fast and prolonged loss in renal function arising from numerous etiologies and pathogenic pathways. Renal fibrosis, defined as the excessive accumulation of collagen and proliferation of fibroblasts within renal tissues, contributes to the structural damage and functional decline of the kidneys, playing a pivotal role in the advancement of Chronic Kidney Disease (CKD). Until now, while continuous renal replacement therapy (CRRT) has been utilized in the management of severe AKI, there remains a dearth of effective targeted therapies for AKI stemming from diverse etiologies. Similarly, the identification of specific biomarkers and pharmacological targets for the treatment of renal fibrosis remains a challenge. Baicalin, a naturally occurring compound classified within the flavonoid group and commonly found in the Chinese herb Scutellaria baicalensis, has shown a range of pharmacological characteristics, such as antioxidant, anti-inflammatory, antifibrotic, antitumor and antiviral effects, as evidenced by research studies. Research shows that Baicalin has potential in treating kidney diseases like AKI and renal fibrosis. This review aims to summarize Baicalin's progress in these areas, including its molecular mechanism, application in treatment, and absorption, distribution, metabolism, and excretion. Baicalin's therapeutic effects are achieved through various pathways, including antioxidant, anti-inflammatory, antifibrosis, and regulation of apoptosis and cell proliferation. Besides, we also hope this review may give some enlightenment for treating AKI and renal fibrosis in clinical practice. [ABSTRACT FROM AUTHOR]

Sirtuins, identified as (NAD+)- dependent class III histone deacetylases, engage in a spectrum of biological functions, encompassing DNA damage repair, oxidative stress, immune modulation, mitochondrial homeostasis, apoptosis and autophagy. Sirtuins play an apoptosis role in regulating cellular operations and overall organism health. Mounting data indicate that dysregulated sirtuin expression is linked to the onset of renal diseases. Effective modulation of sirtuins expression and activity has been shown to improve renal function and attenuate the advancement of kidney diseases. In this review, we present a comprehensive overview of the biological impacts of sirtuins and their molecular targets in regulating renal diseases. Additionally, we detail advancements in elucidating sirtuin roles in the pathophysiology of both chronic and acute renal disorders. We review compounds that modulate sirtuin activity through activation or inhibition, potentially improving outcomes in renal disease. In summary, strategic manipulation of sirtuin activity represents a prospective therapeutic approach for renal diseases. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is defined by a sharp decrease in the estimated glomerular filtration rate (eGFR). However, the impact of medication history on the survival of AKI patients has received little attention. Hence, it is necessary to investigate the potential of medication history as a predictor of survival outcomes among AKI patients in the intensive care unit (ICU). Methods: Critically ill AKI patients were sourced from the MIMIC-IV database. To ascertain significant, drug-related, independent predictors of survival, univariate Cox analysis and stepwise Cox regression were performed. Based on the identified predictor, a nomogram was developed to estimate the individualized survival probability for AKI patients. Additionally, to address potential confounders among patients with medications referenced in the nomogram, a propensity score matching procedure was applied. Ultimately, a comparative analysis was performed to elucidate the prognostic disparities among these patient subgroups. Results: This study enrolled 1,208 patients and developed a nomogram incorporating oxygen flow rate, respiratory frequency, continuous venovenous hemodiafiltration status, age, and medication use (including ibuprofen, epinephrine, cefazolin, warfarin, and vasopressin). The predictive model demonstrated diagnostic accuracy, with AUC values for 1-year, 3-year, and 5-year survival among AKI patients of 0.827, 0.799, and 0.777 in the training dataset, and 0.760, 0.743, and 0.740 in the internal validation dataset, respectively. Kaplan–Meier survival analyses revealed significant differences in survival outcomes among AKI patients based on their exposure to different medications. Conclusions: In summary, the developed prediction model demonstrated accuracy for AKI patients in the ICU and helped clinical decision-making. However, future studies will require external validation to confirm these findings. [ABSTRACT FROM AUTHOR]

Aims: Endoplasmic reticulum (ER) degradation via autophagy is a process that maintains ER homeostasis when cells are in a state of stress and is associated with many diseases; however, the role of hypoxia inducible factor-1α (HIF-1α)-mediated ER degradation and the related regulatory pathway in acute kidney injury (AKI) still needs to be further established. Results: In the present study, an in vivo AKI model was induced in mice via the ischemia–reperfusion (IR) method. The results revealed that HIF-1α and BNIP3 were increased, and autophagy and ER degradation were activated in the kidneys of AKI mice, whereas HIF-1α knockout significantly inhibited BNIP3, autophagy and ER degradation, accompanied by aggravated kidney injury. Overexpression of HIF-1α in vitro significantly increased BNIP3, autophagy and ER degradation, whereas inhibition of BNIP3 significantly reversed the effects of HIF-1α. In addition, the in vitro inhibition of autophagy with chloroquine significantly reversed the effects of HIF-1α on cell apoptosis. Moreover, selectively overexpressing BNIP3 on the ER membrane significantly increased ER degradation via autophagy and decreased cell apoptosis in vitro. Innovation and Conclusion: These data indicate that HIF-1α/BNIP3-mediated ER degradation via autophagy in tubular cells protects against IR-induced AKI. Antioxid. Redox Signal. 42, 212–227. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a common complication after cardiac surgery and associated with adverse outcomes. The purpose of this study is to construct a nomogram to predict the probability of postoperative AKI in pediatric patients undergoing cardiac surgery. We conducted a single-center retrospective cohort study of 1137 children having cardiac surgery under cardiopulmonary bypass. We randomly divided the included patients into development and validation cohorts at a ratio of 7:3. The least absolute shrinkage and selection operator regression model was used for feature selection. We constructed a multivariable logistic regression model to select predictors and develop a nomogram to predict AKI risk. Discrimination, calibration and clinical benefit of the final prediction model were evaluated in the development and validation cohorts. A simple nomogram was developed to predict risk of postoperative AKI using six predictors including age at operation, cyanosis, CPB duration longer than 120 min, cross-clamp time, baseline albumin and baseline creatinine levels. The area under the receiver operator characteristic curve of the nomogram was 0.739 (95% CI 0.693–0.786) and 0.755 (95% CI 0.694–0.816) for the development and validation cohort, respectively. The calibration curve showed a good correlation between predicted and observed risk of postoperative AKI. Decision curve analysis presented great clinical benefit of the nomogram. This novel nomogram for predicting AKI after pediatric cardiac surgery showed good discrimination, calibration and clinical practicability. [ABSTRACT FROM AUTHOR]

Background and Aims: Sepsis-associated acute kidney injury (SA-AKI) significantly contributes to morbidity and mortality. Current biomarkers have limitations, necessitating the exploration of alternative indicators. This study aims to evaluate various urinary electrolyte parameters to predict SA-AKI. Methods: A prospective observational study included 111 sepsis patients within 24 h of admission. Urinary electrolyte samples were collected, and indices were calculated. Patients were monitored for 7 days to assess for acute kidney injury (AKI) according to Kidney Disease Improving Global Outcomes (KDIGO) definition criteria, mortality rates, and the need for renal replacement therapy. Mann-Whitney U test and Chi-squared test were used to analyse continuous and categorical variables, respectively. Receiver-operating characteristic (ROC) curves were constructed to determine to discriminatory ability of various parameters in predicting AKI. Results: Of 111 patients, 42.3% developed AKI, with a mortality rate of 59.5%. When evaluating urinary parameters, the product of urine sodium and urine creatinine exhibited the maximum full form [area under the receiver operating characteristic (AUROC): 0.66; 95%CI: 0.56, 0.77)], and the parameter of fractional excretion of potassium (FeK) exhibited an AUROC of 0.62 (95%CI: 0.51, 0.72). Furthermore, 2-hour excretion of potassium revealed a statistically significant correlation with 2-hour creatinine clearance (r = 0.62, P < 0.001). Logistic regression models, incorporating Sequential Organ Failure Assessment (SOFA) score, FeK, and urine sodium concentration as variables (P = 0.020, 0.044, and 0.033, respectively), achieved an AUROC of 0.751 in predicting AKI. Conclusion: Urine sodium levels and fractional potassium excretion moderately effectively predict AKI in sepsis patients. Urine potassium excretion correlates with glomerular filtration rate. [ABSTRACT FROM AUTHOR]

Paediatric acute kidney injury (AKI) is common and linked to longer hospitalisation and mortality. We investigated whether a continuous intraoperative infusion of dexmedetomidine, which increases renal blood flow, was associated with a lower risk of postoperative AKI in paediatric patients undergoing noncardiac surgery. This retrospective cohort study included paediatric patients undergoing noncardiac surgery between January 2019 and July 2021. Propensity score matching, based on the participants' baseline characteristics, was used to minimise the potential bias. The primary outcome was AKI within 7 days after surgery. The secondary outcomes included ICU admission, in-hospital mortality, length of hospitalisation, intraoperative bradycardia, and hypotension. The exposure of interest was continuous intraoperative infusion of dexmedetomidine at any dosage or duration. Multivariable logistic regression and linear regression analyses were further used to adjust for residual imbalanced intraoperative factors in the matched cohort. After propensity score matching, we identified 1858/4091 paediatric patients who had received intraoperative dexmedetomidine infusion. Intraoperative dexmedetomidine infusion was associated with a lower risk of AKI (1.4% vs 3.2%; odds ratio 0.43, 95% confidence interval 0.27–0.66; P <0.001), postoperative ICU admission (odds ratio 0.35, 95% confidence interval 0.30–0.42; P <0.001), and shorter hospitalisation (7 [5-10] vs 9 [6-13] days; P <0.001). Intraoperative bradycardia, hypotension, and in-hospital mortality were similar between the matched groups. This retrospective analysis of a single-centre paediatric noncardiac surgery cohort suggests that intraoperative dexmedetomidine infusion was associated with a lower incidence of AKI within 7 days after surgery. ChiCTR2300069115. [ABSTRACT FROM AUTHOR]

Ferroptosis is a type of non-apoptotic regulated cell death characterized by iron accumulation and lipid peroxidation. Cisplatin is an effective chemotherapy drug with several serious side effects including acute kidney injury (AKI). Asprosin is a peptide contributing to metabolism regulation and metabolic disorders. This study aimed to determine the role and mechanism of asprosin in AKI. Cisplatin was used to induce cell damage in mouse renal tubular epithelial (TCMK-1) cells and AKI in C57BL/6 mice. Cisplatin caused asprosin upregulation in cisplatin-treated TCMK-1 cells and mice. In TCMK-1 cells, asprosin overexpression led to iron overload and lipid peroxidation, while asprosin knockdown attenuated cisplatin-induced iron overload, lipid peroxidation and ferroptosis. Exogenous asprosin promoted cell damage and ferroptosis, which were attenuated by ferroptosis inhibitors. Asprosin-induced iron overload, lipid peroxidation, cell damage and SMAD1/5/8 phosphorylation were prevented by bone morphogenetic protein (BMP) type I receptor inhibitor. Integrin antagonist prevented asprosin-induced SMAD1/5/8 phosphorylation, and asprosin can specifically bind to integrin β3. Inhibition of integrin β3 reduced the asprosin-induced increases in Fe2+ and MDA levels. Asprosin knockdown relieved cisplatin-induced hepcidin upregulation, while hepcidin knockdown attenuated asprosin-induced iron overload, lipid peroxidation and ferroptosis. In cisplatin-induced AKI mice, specific knockdown of asprosin in the kidney not only attenuated renal dysfunction and damage, but also alleviated iron overload, lipid peroxidation and ferroptosis. These results indicated that excessively increased asprosin promotes TCMK-1 cells ferroptosis and damage via integrin β3/BMP/hepcidin-mediated iron overload and lipid peroxidation. Silencing of asprosin attenuates renal injury and dysfunction in cisplatin-induced AKI by inhibiting ferroptosis. [Display omitted] • Asprosin promotes iron overload, lipid peroxidation and ferroptosis in TCMK-1 cells. • The effects of asprosin are mediated by the integrin β3/BMP/hepcidin signaling pathway. • Inhibition of asprosin expression attenuates renal injury and dysfunction. • Inhibition of asprosin expression attenuates ferroptosis in cisplatin-induced AKI. • This study provides new ideas for the treatment and prevention of AKI. [ABSTRACT FROM AUTHOR]

Background: Pediatric cardiac surgery-associated acute kidney injury (CS-AKI) is common with variable association with outcomes, possibly because transient serum creatinine (SCr) elevations are unrelated to kidney disease. Sub-phenotypes of CS-AKI with biomarker integration may provide prognostic enrichment. This study aims to determine if combining early postoperative urine neutrophil gelatinase-associated lipocalin (uNGAL) and SCr into sub-phenotypes strengthens associations with AKI and outcomes. We hypothesized that patients with early subclinical (uNGAL + , SCr −) or damage (uNGAL + , SCr +) CS-AKI would have more postoperative day 2–4 KDIGO-defined AKI and worse clinical outcomes than patients with early functional AKI (uNGAL − , SCr +). Methods: Two-center prospective observational study evaluating combinations of early uNGAL (8–12 h from ICU admission, ≥ 150 ng/mL) and early postoperative (≤ 8 h of admission) KDIGO SCr-defined AKI to predict CS-AKI on postoperative days (POD) 2–4. Four CS-AKI phenotypes were derived (uNGAL − /SCr − ; uNGAL + /SCr − ; uNGAL − /SCr + and uNGAL + /SCr +). The primary outcome was POD2–4 KDIGO SCr-defined CS-AKI. Secondary outcomes included ventilator and intensive care unit-free days (maximum 28). Results: Four hundred seventy-six patients (median age 4.8 [IQR 1.4–30.4] months, 39% female) were included. POD2–4 AKI occurred in 44 (9.2%). 27% were uNGAL + /SCr − and 0.4% (n = 2) uNGAL + /SCr +. The adjusted odds of POD2–4 AKI was ninefold higher (aOR: 9.09, 95%CI: 3.84–21.53) in uNGAL + /SCr − when compared to uNGAL − /SCr −. uNGAL + /SCr − was associated with fewer ventilator-free (aOR: 0.30, 95%CI: 0.19–0.48) and ICU-free days (aOR: 0.41, 95%CI: 0.26–0.66) when compared to uNGAL − /SCr −. Conclusion: Early postoperative uNGAL, regardless of SCr elevation, refines risk assessment for pediatric POD2–4 CS-AKI and associated morbidity, enabling earlier AKI identification and prognostics. [ABSTRACT FROM AUTHOR]

Background: Elevated cefepime blood concentrations can cause neurotoxicity in adults. The consequences of elevated cefepime concentrations among pediatric patients are unknown. Future exploration of such effects requires first identifying patients at risk for elevated cefepime exposure. We investigated the role of acute kidney injury as a risk factor for increased cefepime concentrations in critically ill children. Methods: This was a retrospective analysis at a single pediatric intensive care unit. Analyzed patients received at least 24 h of cefepime and had at least two opportunistic samples collected for total cefepime concentration measurement. Individual pharmacokinetic (PK) profiles during treatment courses were reconstructed using Bayesian estimation with an established population PK model. Elevated trough concentration (Cmin) was defined as ≥ 30 mg/L based on adult toxicity studies. The effect of kidney dysfunction on cefepime PK profiles was interrogated using a mixed-effect model. Results: Eighty-seven patients were included, of which 13 (14.9%) had at least one estimated Cmin ≥ 30 mg/L. Patients with elevated Cmin were more likely to have acute kidney injury (AKI) during their critical illness (92% vs. 57%, p = 0.015 for any AKI; 62% vs. 26%, p = 0.019 for severe AKI). Patients who had AKI during critical illness had significantly higher cefepime exposure, as quantified by the area under the concentration–time curve over 24 h (AUC24h) and Cmin. Conclusions: Among critically ill children, AKI is associated with elevated cefepime concentrations. Identifying these high-risk patients is the first step toward evaluating the clinical consequences of such exposures. [ABSTRACT FROM AUTHOR]

Kidney dysfunction is a major determinant of prognosis in patients with decompensated cirrhosis awaiting transplantation. We hypothesized that for identical model for end-stage liver disease (MELD) scores at listing, outcomes before and after liver transplantation may vary if the predominant driver of the MELD score is serum creatinine (Cr) vs. serum bilirubin (Br) or international normalized ratio (INR). We evaluated all adult patients registered for liver transplantation (LT) between 2016–2020 and excluded patients receiving MELD exceptions or undergoing dual organ transplantation. Using K-Means clustering analysis, we classified each patient as MELD-Br, MELD-INR or MELD-Cr depending on the dominant variable for their MELD score. The primary outcome was intent-to-treat (ITT) survival, defined as survival within 1 year from listing with or without LT. MELD scores of LT waitlist registrants were clustered into three subtypes: MELD-Br (n = 13,658), MELD-INR (n = 13,809), and MELD-Cr (n = 12,412). One-year ITT survival rates were 78% (MELD-Br), 75% (MELD-INR), and 65% (MELD-Cr), p < 0.01. ITT survival was lower for each MELD subtype for females compared to males (e.g. MELD-Cr: 63% females vs. 67% males, p < 0.0001). The MELD-Cr subtype had the highest MELD at listing (MELD-Cr 23.4 vs. MELD-Br 19.2 vs. MELD-INR 21.0) and the largest decline in MELD over 3 months (23% vs. 12% vs. 21%). In adjusted analyses including MELD-Na, MELD-Cr was associated with higher waitlist mortality (hazard ratio 1.339, 95% CI 1.279-1.402) and lower LT rates (hazard ratio 0.688, 95% CI 0.664-0.713) compaed to the other subtypes. For equivalent listing practices, registrants with the MELD-Cr subtype have lower ITT survival. MELD subtype may serve as a more sophisticated variable for dynamic assessment of mortality risk and to guide organ allocation. The model for end-stage liver disease (MELD) score is an excellent predictor of waitlist mortality; however, our work highlights that the driver of a patient's MELD score matters and particularly those driven by elevated creatinine are associated with lower 1-year intent-to-treat survival. The 1-year intent-to-treat survival is also lower for women compared to men within the Cr-dominant subtype. These results are important for physicians and patients undergoing LT evaluation as creatinine may serve as a marker of prognosis and even if creatinine levels improve the prognosis remains poor, necessitating discussion about alternative pathways for transplant. Our work also highlights that the type of kidney injury matters, in that those with acute kidney injury were more likely to die or remain on the waitlist than those with chronic kidney disease within the creatinine-dominant subtype. [Display omitted] • Patients with MELD scores dominated by Cr have lower 1 year ITT survival compared to scores dominated by bilirubin or INR. • For each of the subtypes, females have lower 1 year ITT survival compared to males. • Within the MELD-Cr subtype, those with AKI were less likely to get transplanted and more likely to die than those with CKD. [ABSTRACT FROM AUTHOR]

Introduction: Aminoglycosides possess activity against aerobic gram-negative organisms and are often used in combination with beta-lactam antibiotics. Previous studies evaluating combination therapy in gram-negative bacteremia have not shown clear benefits, however antimicrobial resistance was not prevalent in these studies. Our objective is to elucidate potential benefits of adding a single dose of an aminoglycoside to a beta-lactam in patients with gram-negative bacteremia. Methods: This study was a single-center, retrospective, cohort study including patients 18 years old or older and treated for at least 24 hours for a confirmed gram-negative bacteremia. Patients were divided into two groups: receipt of beta-lactam monotherapy (n = 164) and receipt of a beta-lactam in addition to a single dose of an aminoglycoside (n = 79) within 24 hours of bacteremia onset. The primary endpoint was infection-related 30-day mortality per provider documentation. Key secondary outcomes include incidence of acute kidney injury (AKI) and time to improvement of AKI. Data were analyzed using Chi-square or Fisher's exact tests, student's T test, and descriptive statistics as appropriate. Results: The primary outcome occurred in 13/164 vs 2/79 patients in the monotherapy and combination groups (P = 0.10). Incidence of AKI (14% vs. 12%) and time to recovery from AKI (90 hours; IQR [50 – 133] vs 78 hours; IQR [42 – 128]) were comparable between groups (P = 1.00 and P = 0.73, respectively). Conclusions: The addition of a single-dose aminoglycoside was not significantly associated with reduced mortality or increased time to recovery from AKI in our patient population. Larger studies, particularly in more severely ill patient populations, are needed. [ABSTRACT FROM AUTHOR]

Background: Critically ill children are vulnerable to acute kidney injury (AKI) and are often exposed to nephrotoxic medications. Objectives: We aimed to investigate the association between nephrotoxic medications and the risk of AKI in critically ill children admitted to our paediatric intensive care unit (PICU). Methods: Patients aged > 1 month to ≤18 years old were prospectively recruited from 6/2020 to 6/2021. The medication records from 14 days prior to PICU admission to PICU discharge were reviewed. Medication-exposure intensity was defined as the number of concomitant nephrotoxic medications. The relative risk (RR) of nephrotoxic medication exposure indices and other potential predictors for AKI development were determined. Results: Altogether 253 episodes of admissions (median [IQR] age of 4.9 [9.6] years) were enrolled. The AKI incidence was 41.9% and 69.2% of the patients were exposed to ≥1 of the 47 nephrotoxic medications. The total nephrotoxic medication dose (RR: 1.01 [1.00, 1.02]) and medication-exposure intensity (RR: 1.381 [1.101, 1.732]) were significantly associated with AKI development. The risk of AKI increased when the medication-exposure intensity was ≥4 (RR: 3.687 (1.320, 10.301)). During their PICU stay, children with AKI received a higher number (P <.01), total dose (P <.01) and medication exposure intensity (P <.01) of nephrotoxic medications. Children with AKI who received nephrotoxic medications were more likely to have a persistently higher peak-to-baseline ratio (P =.046). Conclusion: Nephrotoxic medication exposure significantly increased the risk of AKI development among critically ill children. The use of nephrotoxic medications among critically ill children at risk for AKI should be monitored frequently. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the impact of a methicillin-resistant Staphylococcus aureus (MRSA) nasal polymerase chain reaction (PCR) protocol on the vancomycin length of therapy (LOT) for skin and soft tissue infections (SSTIs). Design: Retrospective quasi-experimental pre- and post- MRSA nasal PCR protocol implementation study. Setting: Tertiary-care academic medical center in Jacksonville, Florida. Patients: Eligible patients received empiric vancomycin for SSTIs from January 1st to September 30th 2020 (pre-implementation group) and from January 1st to September 30th 2022 (post-implementation group). Intervention: The electronic health system software was modified to provide a best-practice advisory (BPA) prompt to the pharmacist upon order verification of vancomycin for patients with SSTIs. Methods: We reviewed patient records to determine the time from vancomycin prescription to de-escalation. The secondary outcomes were incidence of acute kidney injury (AKI), number of vancomycin levels collected, and hospital length of stay (LOS). Results: The study included 131 patients (pre-implementation, n = 86 and post-implementation, n = 45). There was no significant difference in vancomycin length of therapy (LOT) between implementation groups: mean LOT in days and standard deviation (SD) were 2.7 (1.9) and 2.6 (1.3), respectively, p-value 0.493. Of significance, in the post-implementation group, vancomycin LOT between patients with a negative and positive MRSA PCR were 2.3 (1.1) and 3.9 (1.6), p-value 0.006. There was no difference in secondary outcomes. Conclusion: The utilization of the MRSA nasal PCR to guide vancomycin de-escalation did not significantly change the vancomycin LOT, however in the post-implementation group there was a significant difference in vancomycin LOT between negative and positive MRSA PCRs. [ABSTRACT FROM AUTHOR]

Background: Cefepime is used for the treatment of nosocomial infections and serves as a carbapenem-sparing agent for treating AmpC inducible bacteria. Cefepime induced neurotoxicity (CIN) is a well-documented adverse effect, although data describing the risk of CIN in patients with a history of seizures (HOS) remains limited. Objectives: The primary and secondary objectives were to compare the rates of CIN in patients with and without HOS and identify risk factors associated with CIN, respectively. Methods: This was a retrospective matched cohort study of patients admitted to University Hospital from January 2019 to December 2022 that were initiated on cefepime with and without a baseline HOS. Patients were matched at a rate of 1:1 by age (+/− 5 years), sex, and month of admission (+/− 1 month). Results: A total of 150 patients were included, 75 in each group. There was no statistically significant difference in CIN between the two groups (9 vs 7, P = 0.7923). The only risk factors associated with CIN were age >65 (OR, 5.8 [95% CI, 1.194-27.996]), acute kidney injury (AKI) during cefepime administration (OR, 13.8 [95% CI, 2.528-75.206]), and an intensive care unit (ICU) stay (OR, 8.6 [95% CI, 1.735-42.624]). Conclusion: There was no increased risk of CIN observed in patients with HOS. Patients age >65, AKI while receiving cefepime and those admitted to the ICU were 5.8, 13.8, and 8.6 times more likely to experience CIN. These results suggest that it may be safe to administer cefepime to patients with HOS in the appropriate clinical setting. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common in sepsis and a urine output <0.5 mL/kg/h associated with increased mortality is incorporated into AKI diagnosis. We aimed to identify the urine-output threshold associated with increased AKI incidence and hypothesized that a higher urine output than a specified threshold, which differs from the predominantly used 0.5 mL/kg/h threshold, would be associated with an increased AKI incidence. Methods: This was a post-hoc analysis of a nationwide prospective observational study. This study included adult patients newly diagnosed with sepsis and requiring intensive care. Urine output on the day of sepsis diagnosis was categorized as low, moderate, or high (<0.5, 0.5-1.0, and >1.0 mL/kg/h, respectively), and we compared AKI incidence, renal replacement therapy (RRT) requirement, and 28-day survival by category. Estimated probabilities for these outcomes were also compared after adjusting for patient background and hourly fluid administration. Results: Among 172 eligible patients, AKI occurred in 46.3%, 48.3%, and 53.1% of those with high, moderate, and low urine output, respectively. The probability of AKI was lower in patients with high urine output than in those with low output (43.6% vs 56.5%; P =.028), whereas RRT requirement was lower in patients with high and moderate urine output (11.7% and 12.8% vs 49.1%; P <.001). Patients with low urine output demonstrated significantly lower survival (87.7% vs 82.8% and 67.8%; P =.018). Cubic spline curves for AKI, RRT, and survival prediction indicated different urine-output thresholds, including <1.2 to 1.3 mL/kg/h for AKI and <0.6 to 0.8 mL/kg/h for RRT and mortality risk. Conclusions: Urine output >1.0 mL/kg/h on the day of sepsis diagnosis was associated with lower AKI incidence. The urine-output threshold was higher for developing AKI than for RRT requirement or mortality. [ABSTRACT FROM AUTHOR]

Current adult cardiac surgery guidelines recommend against the routine use of prophylactic intravenous corticosteroids during cardiopulmonary bypass (CPB) due to concerns about myocardial injury, despite their potential to reduce postoperative atrial fibrillation. Traditionally, a high dose of 1,000 mg of methylprednisolone was used to attenuate the inflammatory response associated with CPB. Our institution aligned with guideline recommendations and gradually reduced methylprednisolone dosages; thus, we reevaluated the impact on postoperative clinical outcomes. Our study reviewed 1341 cases from a total of 1680 adult cardiac surgeries performed between June 2019 and May 2022 after excluding cases with off-pump procedures, ventricular assist device implantations, heart transplants, and aortic surgeries requiring systemic circulatory arrest. The study timely sorted periods including a baseline data from 2018, and other three periods since 2019 to analyze the effects of three different methylprednisolone dosage: 0 mg, 500 mg, and 1000 mg. We assessed the annual trends in methylprednisolone administration and compared morbidity and mortality rates across the groups. We observed a significant decline in steroid use, with no-steroid surgeries increasing from 23% to 66.5% by period 3. Despite the decreased use of steroids, our study showed no increase in mortality, new-onset atrial fibrillation, acute kidney injury, cerebrovascular event and prolonged ventilation when compared to baseline data. Notably, less surgical site infection rate was observed in the no-steroid group. The data indicates that a reduction or discontinuation of steroids during CPB can be performed without compromising patient outcomes. This could support a transition towards a more conservative use of steroids in adult cardiac surgery, aligning with current guidelines, and potentially reducing certain postoperative complications. [ABSTRACT FROM AUTHOR]

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Introduction: Exertional rhabdomyolysis (ER) is the breakdown of muscle cells that occurs after intensive physical activity. Although a cautious and gradual return to physical activity (RTPA) is recommended after an episode of ER, physical sequelae are reported long afterwards. Case report: We present the case of a 31-year-old untrained amateur runner with no prior medical history who developed heat stroke, ER, and acute kidney failure on the occasion of a half-marathon. Three months later, whereas the patient was symptom-free and CK levels were normal, an MRI revealed typical signs of rhabdomyolysis, which normalized thereafter. Discussion: Given that clinical and biological data inform RTPA decisions, the delay between clinical biological and MRI normalization may cause an RTPA to be initiated prior to full muscle recovery, which could account for the symptoms' prolonged persistence. In sportspeople who have recovered and their CK blood levels are returned to normal, MRI data could defer the RTPA if MRI abnormalities persist or, conversely, give it the green light. BRIEF SUMMARY STATEMENT: In the event of exertional rhabdomyolysis following a race, the presence of muscular lesions on MRI, even if the patient feels healed and creatine kinase levels have returned to normal, should postpone the return to physical activity. [ABSTRACT FROM AUTHOR]

Copyright of Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Estimated glomerular filtration rate (eGFR) decline is associated with negative health outcomes, but the use of decision tree algorithms to predict eGFR decline is underreported. Among patients hospitalized during the first year of the COVID-19 pandemic, it remains unclear which individuals are at the greatest risk of eGFR decline after discharge. We conducted a retrospective cohort study on patients hospitalized at Stony Brook University Hospital in 2020 who were followed for 36 months post discharge. Random Forest (RF) identified the top ten features associated with fast eGFR decline. Logistic regression (LR) and Classification and Regression Trees (CART) were then employed to uncover the relative importance of these top features and identify the highest risk patients. In the cohort of 1,747 hospital survivors, 61.6% experienced fast eGFR decline, which was associated with younger age, higher baseline eGFR, and acute kidney injury (AKI). Multivariate LR analysis showed that older age was associated with lower odds of fast eGFR decline whereas length of hospitalization and vasopressor use with greater odds. CART analysis identified length of hospitalization as the most important factor and that patients with AKI and hospitalization of 27 days or more were at highest risk. After grouping by ICU and COVID-19 status and propensity score matching for demographics, these risk factors of fast eGFR decline remained consistent. CART analysis can help identify patient subgroups with the highest risk of post-discharge eGFR decline. Clinicians should consider the length of hospitalization in post-discharge monitoring of kidney function. [ABSTRACT FROM AUTHOR]

Background: The "weekend effect" on hospital admissions has been extensively studied, showing increased risks for patients admitted on weekends than those admitted on weekdays. We aimed to assess the "weekend effect" on in-hospital outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). Methods: A nationwide cohort study was conducted using the National Inpatient Sample Database. We identified 82,094 eligible patients aged ≥ 18 years admitted for TAVR between 2013 and 2021. Patients were grouped into weekend or weekday cohorts based on day of admission. Propensity score matching (PSM) and multivariate regression models were employed to evaluate outcomes. After PSM, 2,688 weekend admissions and 13,440 weekday admissions were included in the analyses. Results: Multivariable regression, adjusted for propensity score, revealed that weekend admission was associated with 45% higher odds of in-hospital mortality (adjusted odds ratio: 1.45; 95% confidence interval: 1.13–1.85). Significant heterogeneity in mortality was observed based on admission urgency, with a 3.27 times higher increased risk of death observed for elective admissions on weekends than on weekdays (P for interaction = 0.001). Moreover, weekend admissions had significantly higher adjusted odds for cardiogenic shock, permanent pacemaker implantation, endocarditis, acute kidney injury, acute ischemic stroke, and blood transfusion. There was a trend of higher in-hospital mortality for weekend over weekday admissions throughout the study period. Conclusions: Weekend admissions for TAVR had higher mortality, complications, and resource utilization, particularly in elective cases. Our findings suggest that patients admitted for TAVR during weekends are at high risk and warrant special attention. [ABSTRACT FROM AUTHOR]

Introduction: Delayed graft function (DGF) shortens the survival time of transplanted kidneys and increases the risk of rejection. Current methods are inadequate in predicting DGF. More precise tools are required to assess kidney suitability for transplantation. Cold-inducible RNA-binding protein (CIRBP) expression has been linked to acute kidney injury, suggesting its potential as a new biomarker for transplanted kidney function. Methods: We included deceased donors and recipients who had undergone successful kidney transplantation between 2016 and 2019. Recipients and their paired donors are assigned to either the DGF or immediate graft function (IGF) group, based on the recipient's recovery of graft renal function. Donor plasma CIRBP levels were measured using an enzyme-linked immunosorbent assay kit to assess their relationships with DGF. Results: Donor plasma CIRBP concentrations in the DGF group were approximately twice as high as those in the IGF group (6.82 vs. 3.44; P<0.001). DGF occurred in all cases where CIRBP concentrations exceeded 7.92 ng/mL. Furthermore, univariate and multivariate analyses (odds ratio [OR]=1.660; P<0.001) confirmed that donor plasma CIRBP level was an independent risk factor for DGF. Additionally, higher CIRBP levels were associated with increased plasma creatinine at 6 months (R²=0.08; P<0.001), and survival analysis showed shorter kidney survival in recipients with DGF (P=0.002). Conclusions: This study demonstrated that donor plasma CIRBP levels can effectively predict the occurrence of DGF. CIRBP is a potential novel biomarker for evaluating transplanted kidney function. Clinical trial registration: https://clinicaltrials.gov , identifier NCT06641622. [ABSTRACT FROM AUTHOR]

Background: Regionally anticoagulated continuous renal replacement therapy with citrate is the first choice for critically ill patients with acute kidney injury. If citrate that reaches the patient exceeds the metabolic capacity, metabolic alkalosis will follow. Bicarbonate from the treatment fluids will also reach the patient and add to the bicarbonate load. Net buffer load is a parameter calculated by the dialysis machine software from the treatment fluid contents, the fluid flows and the filter properties. Each time the treatment settings are altered the net buffer load will be re-calculated. This parameter is integrated as a static safety parameter in the Prismax version 3 software, and will guide the operator on a possible development of metabolic alkalosis with the current settings. Methods: Algorithms for estimating the net buffer load were developed. Hourly clinical data from electronic medical records from 60 patients' continuous renal replacement treatments at the Adult Intensive Care Unit, Skåne University Hospital, Lund, Sweden was used to simulate net buffer load. The relation between net buffer load and acid base status at steady state was evaluated. Net buffer load was also calculated from three previous studies for comparison to our present cohort. Results: The mean net buffer load was +0.09 ±0.04 mmol/h/kg in the present cohort, and comparable to historic cohorts from literature. We could not establish a correlation to steady state arterial bicarbonate. The pre blood pump citrate containing replacement fluid flow rate was affecting net buffer load most of all parts of the dialysis circuit, with a r2 Pearson correlation coefficient of 0.65 (p<0.001). Conclusion: The net buffer load parameter can alert the operator on the expected impact of the dialysis circuit on patient's acid base status. It was possible to calculate realistic net buffer load values during 60 CRRT treatments. [ABSTRACT FROM AUTHOR]

Background: Although extracorporeal membrane oxygenation (ECMO) is an effective technique for life support, the incidence of acute kidney injury (AKI) during ECMO support remains high. Dexmedetomidine (DEX), which has been widely used for sedation during ECMO, possesses several properties that help reduce the occurrence of AKI. This study aimed to investigate the protective effect of DEX on kidney function during ECMO. Methods: A total of 18 male Sprague–Dawley (SD) rats were randomly divided into three groups: Sham, ECMO, and ECMO + DEX groups. ECMO was established through the right jugular vein for venous drainage and right femoral artery for arterial infusion and lasts for four hours. Hematoxylin and eosin staining was used to evaluate the kidney Paller score for the rats in each group. Enzyme-linked immunosorbent assay was used to measure the levels of kidney injury biomarkers and cytokines in the serum. Reagent kits were used to measure the blood urea nitrogen (BUN) and creatinine (Cr) levels, which helped determine kidney function. Immunohistochemical staining was used to evaluate neutrophil infiltration in the kidney. Results: The pathological Paller score was substantially lower in the ECMO + DEX group. The levels of Kidney Injury Molecule-1 (KIM-1) and N-acetyl-β-D-glucosaminidase (NAG) were also significantly reduced. The kidney functionality, as indicated by BUN and Cr, was significantly improved compared with the ECMO group. The levels of cytokines IL-6, IL-1β, and TNF-α, were also significantly decreased in the ECMO + DEX group. Conclusion: This study demonstrated that dexmedetomidine could reduce inflammatory response and alleviate AKI during ECMO support. [ABSTRACT FROM AUTHOR]

AbstractIntroductionPatientsDiscussionConclusionsSotalol is a beta-adrenoceptor blocking drug with unique physical and pharmacologic properties. Unlike most beta-adrenoceptor blocking drugs, sotalol is amenable to extracorporeal removal and causes QT interval prolongation and ventricular dysrhythmias. These properties have implications for treating sotalol poisoning.Patient 1: A man in his seventh decade of life overdosed on sotalol 9 g and presented with bradycardia, hypotension, QT interval >600 ms and transient ventricular tachycardia. Dopamine, isoprenaline (isoproterenol), and a transvenous pacemaker were used instead of high-dose insulin due to the risk of iatrogenic hypokalemia. Hemodynamics improved, and the pacemaker was removed six days later. Patient 2: A woman in her seventh decade of life on sotalol presented with hypotension in the setting of anuric acute kidney failure. Hypotension worsened after administration of additional sotalol. Hemodialysis was performed for refractory hypotension, followed by improvement in hemodynamics and kidney function.High-dose insulin, a standard therapy in beta-adrenoceptor blocking drug poisoning, causes hypokalemia, which may exacerbate QT interval prolongation and ventricular dysrhythmias in patients with sotalol poisoning. Sotalol is cleared renally and is amenable to extracorporeal removal; hemodialysis may be a useful therapy in patients with cardiotoxicity and concomitant kidney injury.Chronotropes and overdrive pacing may be preferred therapies for patients with severe sotalol poisoning. If concomitant kidney injury occurs, hemodialysis may be a useful adjunctive therapy. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is a frequent clinical complication lacking early diagnostic tests and effective treatments. Novel biomarkers have shown promise for enabling earlier detection, risk stratification, and guiding management of AKI. We conducted a systematic review to synthesize evidence on the efficacy of novel biomarkers for AKI detection and management. Database searches yielded 17 relevant studies which were critically appraised. Key themes were biomarker efficacy in predicting AKI risk and severity before functional changes; potential to improve clinical management through earlier diagnosis, prognostic enrichment, and guiding interventions; emerging roles as therapeutic targets and prognostic tools; and ongoing challenges requiring further validation. Overall, novel biomarkers like neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and cell cycle arrest markers ([TIMP-2] •[IGFBP7]) demonstrate capability for very early AKI prediction and accurate risk stratification. Their incorporation has potential to facilitate timely targeted interventions and personalized management. However, factors influencing biomarker performance, optimal cutoffs, cost-effectiveness, and impact on patient outcomes require robust validation across diverse settings before widespread implementation. Addressing these limitations through ongoing research can help translate novel biomarkers into improved detection, prognosis, and management of AKI in clinical practice. [ABSTRACT FROM AUTHOR]

Background: The optimal pharmacokinetic and pharmacodynamic (PK/PD) parameters of vancomycin that can improve outcomes in enterococcal infections remain controversial. To clarify the therapeutic target for this antibiotic, this study aimed to determine vancomycin PK/PD parameters associated with efficacy in the early (during 72 h) or later (after 72 h) phase of treatment and nephrotoxicity in enterococcal bloodstream infection patients. Methods: This multicenter retrospective study reviewed medical records of patients with enterococcal bloodstream infections treated with intravenous vancomycin infusion for at least 72 h between January 2016 and March 2024 at Phramongkutklao Hospital or Nopparatrajathanee Hospital in Bangkok, and Rachaburi Hospital in Rachaburi Province, Thailand. Patients with data available on serum vancomycin concentration were analyzed. The primary outcomes were 30-day mortality and acute kidney injury. The estimates of the mean 24-h area under the curve in the first 72 h (AUC24) and in steady state (AUCss) were determined by Bayesian theorem. Results: Overall, 201 vancomycin concentrations were measured within the first 72 h after vancomycin treatment, while 156 were in a steady state (> 72 h). According to Classification and Regression Tree analysis, vancomycin AUC at 420 mg·h/l was the PK/PD target for 30-day mortality. Results reveal that patients with AUC24 (early phase) and AUCss < 420 mg·h/l (later phase) had significantly higher 14-day, 30-day, and in-hospital mortality than AUC ≥ 420 mg·h/l groups. In addition, patients with AUC24 ≥ 420 mg·h/l in the early phase had significantly reduced microbiological failure (p = 0.004). Patients with AUC ≥ 700 mg·h/l in early and later phases had significantly increased acute kidney injury risk. In addition, patients receiving concomitant nephrotoxic drugs had an AUC cutoff value of 650 mg·h/l. Multivariate Cox regression analysis showed that vancomycin AUCss < 420 mg·h/l, unknown source of bacteremia, and acute kidney injury were significantly associated with 30-day mortality. Conclusions: AUC 420–650 mg·h/l in early and later phases was the target of vancomycin's PK/PD in enterococcal bacteremia patients for efficacy and to prevent acute kidney injury. This study suggests close monitoring of vancomycin levels to ensure efficacy and safety. [ABSTRACT FROM AUTHOR]

Background/purpose: Early detection of severe dengue (SD) and appropriate management are crucial in reducing the case fatality rate. The objective of this study was to investigate the clinical characteristics of SD and identify independent risk factors associated with mortality among SD patients. Methods: A retrospective study was conducted at two medical center hospitals between 2002 and 2019, involving patients aged ≧18 years with laboratory-confirmed SD. Results: This study included 294 patients with SD, of whom 203 (69%) survived and 91 (31%) died. Among the 294 SD patients, 103 (35%) experienced acute kidney injury, 54 (18.4%) had pneumonia, and 19 (6.5%) had bacteremia. Among the 286 patients with available alanine aminotransferase (ALT) data, 41 (14.3%) experienced severe hepatitis (ALT>1000U/L). The median time from illness onset to death among the 91 SD patients who died was 5 days. Multivariable regression analysis revealed increasing odds of death associated with older age (odds ratio [OR], 1.037; 95% confidence interval [CI], 1.009–1.066), altered consciousness (OR, 8.591; 95% CI, 2.914–25.330), gastrointestinal bleeding (OR, 1.939; 95% CI, 1.037–3.626), and leukocytosis (OR, 2.504; 95% CI, 1.124–5.578) upon arrival, as well as organ impairment during hospitalization, including acute kidney injury (OR, 2.627; 95% CI, 1.373–5.028), severe hepatitis (OR, 5.324; 95% CI, 2.199–12.889), and pneumonia (OR, 2.250; 95% CI, 1.054–4.802). Conclusions: Our findings underscore the importance of early recognition and intervention by frontline physicians in identifying SD patients at high risk of mortality. This information can significantly contribute to reducing fatalities and improving the overall management of SD cases. Author summary: The early identification of severe dengue (SD) patients who are at high risk of mortality is crucial for frontline physicians to deliver timely and intensive clinical interventions. This study is particularly significant as it focuses on SD patients and explores the factors associated with mortality, aiming to reduce preventable deaths within this specific patient group. We have pinpointed several independent risk factors that are predictive of mortality outcomes, including advanced age, altered consciousness, elevated leukocyte counts, and gastrointestinal bleeding upon admission. Addressing these risk factors at the initial presentation is critical for mitigating the severity of SD and decreasing mortality rates. Additionally, the development of acute kidney injury, severe hepatitis, and pneumonia during hospitalization has been identified as significant prognostic indicators. Prompt recognition of signs of organ hypoperfusion and the implementation of intensive supportive management to prevent further deterioration are essential strategies to reduce mortality among SD patients. These insights are particularly vital for regions with limited medical resources, enabling healthcare providers to efficiently identify and prioritize SD patients at increased risk of mortality. [ABSTRACT FROM AUTHOR]

Background: Occurrence of life-threatening scorpion sting in adults is a rare entity compared with children. Different cases of organ failure following scorpion sting have been reported but complications, such as acute toxic myocarditis, cardiogenic shock, pulmonary edema, acute kidney injury and toxic hepatitis occurring simultaneously in adult patients is exceedingly rare with no prior documented similar report. This case report explores the unique presentation of these complications occurring simultaneously and their management in resource limited setting. Case presentation: A 31-year-old Eritrean female came to our emergency room with severe respiratory distress, persistent retching, drenching sweating, generalized pain and unrecordable blood pressure 12 hours after scorpion sting. Electrocardiography revealed signs of diffuse acute myocarditis. The diagnosis of cardiogenic shock and pulmonary edema owing to scorpion sting envenomation was made. The patient also developed acute kidney injury and toxic hepatitis. She recovered well after 10 days of hospital stay and further follow-up, with supportive management and scorpion antivenom. To date, over a period of more than 2 years the patient has no new complaint or complication. Conclusion: This case report highlights the clinical novelty of multiorgan failure following scorpion sting in adults. The unique presentation of acute toxic myocarditis, cardiogenic shock, pulmonary edema, acute kidney injury and toxic hepatitis in a 31-year-old female underscores the possibility of scorpion sting causing such life threatening envenomation after delayed presentation. This case contributes to the understanding of atypical presentations of scorpion sting in adults. [ABSTRACT FROM AUTHOR]

Optimal fluid strategy for laparoscopic donor nephrectomy (LDN) remains unclear. LDN has been a domain for liberal fluid management to ensure graft perfusion, but this can result in adverse outcomes due to fluid overload. We compared postoperative outcome of living kidney donors according to the intraoperative fluid management. Five hundred and five LDNs performed over a six-year period at a tertiary hospital were analyzed. Donors were divided into tertiles according to intraoperative crystalloid infusion rate (ml/kg/hr), and associations between the tertile and outcomes were investigated with inverse probability of treatment weighting with entropy balancing. Primary outcome was maximal rise of serum creatinine (sCr). Secondary outcomes were sCr rise meeting Acute Kidney Injury (AKI) criteria, time to reach minimal sCr, and length of hospital stay. The following covariates were used: age, sex, body weight, height, diabetes mellitus, hypertension, preoperative estimated glomerular filtration rate, operation duration, surgeon, nephrectomy side, and estimated blood loss. Median intraoperative crystalloid infusion rate was 3.5, 4.6, and 6.0 ml/kg/hr in the first, second, and third tertile, respectively (group 1, 2, and 3). Maximal rise of sCr did not differ between groups (P = 0.274). Twofold increase in sCr (equivalent to stage 2 AKI) during the first week and prolonged hospitalization were most frequent in group 1 [7.8 vs. 1.1 vs. 1.5%, P = 0.004; 7.9 vs. 3.1 vs. 0.7%, P = 0.003]. Time to reach minimal sCr was longest in group 1. No differences were found in recipient early renal function. Hypovolemia is associated with poor postoperative outcomes after LDN. Efforts to find the optimal fluid management should be continued. [ABSTRACT FROM AUTHOR]

This study is designed to assess the effect of root extract of P. ginseng on kidney tissue injury attributed to cisplatin and its molecular mechanism involved in this process in the AKI rat model. Twenty-four male Wistar rats were randomly allocated into 4 experimental groups including: the control group, the cisplatin group, the extract 100 mg/kg group, and the extract 200 mg/kg group. The duration of the investigation was 7 days, and all rats except the control group received a single dose of 10 mg/kg cisplatin on the 4th day. Our findings exhibited a significant reduction in blood concentration of creatinine in extract groups compared to the cisplatin group. In the cisplatin group, severe renal histopathological alterations were observed compared to the control group. In extract groups, significantly less tissue damage was observed than in the cisplatin group. Ginseng extract 200 showed minimal tissue damage as compared to extract 100. The expression of p21, p27, p53, TIMP2, IGFBP7, and NF-κB decreased significantly in extract groups compared to the cisplatin group. Our findings displayed amelioration of cisplatin-induced AKI and dose-dependent decrease of the NF-κB gene expression and cell death-inducing genes by administration of P. ginseng extract. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is common in critically ill patients and is associated with increased morbidity and mortality. Its complications often require renal replacement therapy (RRT). Invasive mechanical ventilation (IMV) and infections are considered risk factors for the occurrence of AKI. The use of IMV and non-invasive ventilation (NIV) has changed over the course of the pandemic. Concomitant with this change in treatment a reduction in the incidences of AKI and RRT was observed. We aimed to investigate the impact of IMV on RRT initiation by comparing critically ill patients with and without COVID-19. Furthermore, we wanted to investigate the rates and timing of RRT as well as the outcome of patients, who were treated with RRT. Results: A total of 8,678 patients were included, of which 555 (12.8%) in the COVID-19 and 554 (12.8%) in the control group were treated with RRT. In the first week of ICU stay the COVID-19 patients showed a significantly lower probability for RRT initiation (day 1: p < 0.0001, day 2: p = 0.021). However, after day 7 a reversed HR was found. In mechanically ventilated patients the risk was significantly higher for the initiation of RRT over the entire stay. While in non-COVID-19 patients this was a non-significant trend, in COVID-19 patients the risk for RRT was significantly increased. The median delay between initiation of IMV and requirement of RRT was observed to be longer in COVID-19 patients (5 days [IQR: 2–11] vs. 2 days [IQR: 1–5]). The analysis restricted to patients with RRT showed a significantly higher risk for ICU death in patients requiring IMV compared to patients without IMV. Conclusion: The analysis demonstrated that IMV as well as COVID-19 are associated with an increased risk for initiation of RRT. The association between IMV and risk of RRT initiation was given for all investigated time intervals. Additionally, COVID-19 patients showed an increased risk for RRT initiation during the entire ICU stay within patients admitted to an ICU due to respiratory disease. In COVID-19 patients treated with RRT, the risk of death was significantly higher compared to non-COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Oliguric acute kidney injury (AKI) is one of the critical conditions which needs emergent treatment due to the lack of the capacity of excreting toxins and fluids, and plasma membrane bleb formation is considered as one of the characteristic morphologic alterations in ischemic AKI in both animal models and human. We present here an autopsy case with clear electron microscopy images capturing a definitive instance of blebbing in ischemic AKI. Case presentation: A 66-year-old man was admitted for oliguric AKI with nephrotic syndrome (NS). Because of the existence of hematuria with red blood cell casts and rapid deterioration of renal function and severe systemic symptoms such as loss of appetite and general fatigue, we started immunosuppressive therapy with steroids, considering a vasculitis-like condition with NS, and hemodialysis was also started for oliguria. However, he suddenly died of hemorrhagic shock due to gastric ulcer. Histological findings of the kidney by autopsy showed segmental sclerosis and acute tubular necrosis (ATN) in paraffin sections, which suggests that this is the case with ATN showing oliguric AKI as a clinical presentation. Interestingly, in electron microscopical study, not only apical membrane blebbing but also numerous cytoplasmic bodies were observed in proximal tubules (PT), and this bleb formation was also observed as foamy blebs in the Toluidine blue stained Epon section, where it appeared to fill the tubular lumen. Conclusion: Our distinct finding of bleb formation with tubular obstruction strongly indicates that blebbing could be related to the mechanism of oliguric AKI in human, which supports the tubular obstruction theory as a contributing factor to the pathogenesis of ischemic AKI. [ABSTRACT FROM AUTHOR]

Background: Ursodeoxycholic acid (UDCA), traditionally recognized for its hepatoprotective effects, has also shown potential in protecting kidney injury. This study aimed to evaluate the protective effects of UDCA against sepsis-induced acute kidney injury (AKI) and to elucidate the underlying mechanisms. Methods: Sixty male C57BL/6 N mice were utilized to establish a sepsis-induced AKI model through intravenous injection of lipopolysaccharides (LPS, 10 mg/kg). UDCA (15, 30, and 60 mg/kg) was administered intraperitoneally once daily for 7 days before LPS injection. Kidney injury was evaluated by HE staining and biochemical markers, including serum creatinine (Cr), blood urea nitrogen (BUN), urinary protein, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), N-acetyl-β-D-glucosaminidase (NAG), and retinol binding protein (RBP). Oxidative stress parameters and nuclear factor erythroid 2-related factor 2 (Nrf2)/ heme oxygenase-1 (HO-1) pathway, pro-inflammatory cytokines and nuclear factor-kappa B (NF-κB) pathway were also evaluated. Additionally, HK-2 cells were treated with LPS in vitro, and cell viability and apoptosis were detected using CCK-8 kit and flow cytometer, respectively. Results: UDCA significantly attenuated LPS-induced renal histopathological damage and improved renal function, as evidenced by reduction in serum Cr, BUN, and urinary protein levels. UDCA also up-regulated the protein expression of zonula occludens-1 (ZO-1) and Ezrin in the kidney, and reduced the urinary levels of NGAL, KIM-1, NAG, and RBP. Moreover, UDCA inhibited NF-κB p65 phosphorylation and reduced pro-inflammatory cytokines levels (TNF-α, IL-1β, and IL-6) in both serum and kidney. UDCA alleviated oxidative stress by activating the Nrf2/HO-1 pathway in the kidney. In vitro, UDCA reduced LPS-induced cell injury and apoptosis in HK-2 cells, with these protective effects being blocked by the Nrf2 inhibitor ML385. Conclusions: Our present study demonstrated that UDCA exerts protective effects against sepsis-induced AKI by attenuating oxidative stress and inflammation, primarily through the activation of the Nrf2/HO-1 pathway and inhibition of the NF-κB pathway. These findings highlight the therapeutic potential of UDCA in preventing sepsis-induced AKI. [ABSTRACT FROM AUTHOR]

Marked by iron buildup and lipid peroxidation, ferroptosis is a relatively new regulatory cell death (RCD) pathway. Many diseases like cancer, myocardial ischemia-reperfusion injury (MIRI), neurological disorders and acute renal failure (AKI) are corelated with ferroptosis. The main molecular processes of ferroptosis discovered yet will be presented here, along with the approaches in which it interacts with tumour-associated signaling pathways and its uses in systemic therapy, radiation therapy, and immunotherapy managing tumors. [ABSTRACT FROM AUTHOR]

Background: Renal fibrosis is crucial in the progression of chronic kidney disease (CKD) to end-stage renal failure. Geniposide, an iridoid glycoside, has shown therapeutic potential in acute kidney injury, diabetic nephropathy, and atherosclerosis. The aim of this study was to investigate the role of geniposide in renal fibrosis and its underlying mechanisms. Methods: The network pharmacology and molecular docking methods were used to identify potential targets and pathways of geniposide for treating renal fibrosis. In vivo, the unilateral ureteral obstruction (UUO) mouse model was treated with geniposide. In vitro, TGF-β1-stimulated human renal tubular epithelial (HK-2) cells were applied for validation. HE, PAS, Masson, and immunohistochemistry staining were performed to evaluate its effects on the kidneys of UUO mice. RT-qPCR and western blotting were used to detect the expression of hub genes and signaling pathways. Results: 101 overlapping genes were identified, with the top 10 including AKT1, MMP9, GAPDH, BCL2, TNF, CASP3, SRC, EGFR, IL-1β, and STAT1. GO analysis suggested that these key targets were mainly involved in cell proliferation and apoptosis. KEGG analysis revealed that the PI3K/AKT, MAPK, and Rap1 signaling pathways were associated with geniposide against renal fibrosis. Molecular docking suggested a strong binding affinity of geniposide to the hub genes. In vivo experiments showed that geniposide ameliorated kidney injury and fibrosis, and inhibited the mRNA levels of AKT1, MMP9, BCL2, and TNF. In addition, geniposide inhibited the activation of the PI3K/AKT signaling pathway, thereby suppressing renal fibrosis in UUO mice and TGF-β1-induced HK-2 cells. Conclusions: Geniposide can attenuate renal fibrosis by inhibiting the PI3K/AKT pathway, suggesting its potential as a therapeutic agent for renal fibrosis. [ABSTRACT FROM AUTHOR]

Introduction: Electrical injuries (EIs) represent a significant clinical challenge due to their complex pathophysiology and variable presentation, ranging from minor burns to severe internal organ damage. Despite their prevalence in both; domestic and occupational settings, there remains a rareness of systematic guidelines and comprehensive literature to aid clinicians in effectively managing these injuries. Understanding these factors is crucial for developing protocols that can mitigate the risk of delayed complications, such as cardiac arrhythmias, in patients who initially appear stable. Objectives: This study aims to elucidate the epidemiology, clinical outcomes, and predictors of severe presentation in EIs, providing insights to improve patient assessment and management strategies. Methods: A retrospective study was conducted over 4 years. Data were collected from standardized medical records. The group of patients with severe complications included those who presented a life-threatening cardiac, respiratory, neurological, or biological impairment or died within the first 48 h of the EI. Results: We enrolled 118 cases of electrical injury (EI). Ages ranged from 4 to 82 years, with 31.3% under 15. EI incidence peaked in summer, with 63.5% being home accidents. High-voltage injuries occurred in 13.6%. The most common ED complaints were burns in children (59.5%) and trauma in adults (48.1%). ECG abnormalities correlated with tetany (p = 0.016), and palpitations (p = 0.014). Complications included cardiac arrest (n = 8), rhabdomyolysis (n = 23), and acute renal injury (n = 9). Severe EI was linked to respiratory distress and creatine kinase levels higher than ≥ 253 UI/l. A normal ECG within 1 h post-injury was correlated to a low risk of severe EI. At 2-year follow-up, 43.9% of survivors reported aesthetic sequelae, 25.3% had psychological disorders, and 7% of adults could not return to their previous occupations. Conclusion: EIs are frequent, with diverse clinical presentations requiring multidisciplinary care. Awareness of potential delayed complications is essential, and prevention is crucial. [ABSTRACT FROM AUTHOR]

Background: Marathon training and running have many beneficial effects on human health and physical fitness; however, they also pose risks. To date, no comprehensive review regarding both the benefits and risks of marathon running on different organ systems has been published. Main Body: The aim of this review was to provide a comprehensive review of the benefits and risks of marathon training and racing on different organ systems. A predefined search strategy including keywords (e.g., marathon, cardiovascular system, etc.) and free text search was used. Articles covering running regardless of sex, age, performance level, and event type (e.g., road races, mountain marathons) were considered, whereas articles examining only cycling, triathlon, stress-tests or other sports were excluded. In total, we found 1021 articles in PubMed, Scopus, and Google Scholar, of which 329 studies were included in this review. Overall, marathon training offers several benefits for different organ systems and reduces all-cause mortality. As such, it improves cardiovascular risk factors, leads to favorable cardiac adaptations, enhances lung function, and improves quality of life in chronic kidney disease patients. It also enhances gastrointestinal mobility and reduces the risk of specific tumors such as colorectal cancer and hepatocellular carcinoma. Marathon training enhances bone health and skeletal muscle metabolism. It further positively affects hematopoiesis and cytotoxic abilities of natural killer cells, and may act neuroprotective on a long-term basis. After a marathon, changes in biomarkers suggesting pathological events in certain organ systems such as cardiovascular, renal, gastrointestinal, liver, hematological, immune, musculoskeletal, central nervous, and endocrine systems can often be observed. Mostly, these changes are limited to 1–3 days post-race and usually normalize within a week. Moreover, marathon running poses the risk of serious adverse events such as sudden cardiac death or acute liver failure. Concerning lung function, a decrease after a marathon race was observed. Acute kidney injury, as well as electrolyte imbalances, are relatively common amongst marathon finishers. Many runners complain of gastrointestinal symptoms during or after long-distance running. Many runners suffer from running-related musculoskeletal injuries often impairing performance. A marathon is often accompanied by an acute inflammatory response with transient immunosuppression, making runners susceptible to infections. Also, hormonal alterations such as increased cortisol levels or decreased testosterone levels immediately after a race are observed. Disturbances in sleep patterns are commonly found in marathon runners leading up to or directly after the race. Conclusion: All in all, marathon training is generally safe for human health and individual organ systems. Considering the high popularity of marathon running, these findings supply athletes, coaches, sports scientists, and sports medicine practitioners with practical applications. Further large-scale studies examining long-term effects on the cardiovascular, renal, and other system are needed. Key Points: Marathon training and racing affects several organ systems in a positive and negative way. The most common problems during or after a marathon are acute kidney injury, gastrointestinal distress, running-related injuries, and upper respiratory tract infections. Generally, marathon training is safe for different organ systems and its positive effects outweigh any potential harms [ABSTRACT FROM AUTHOR]

Thrombotic microangiopathy (TMA) is a severe condition characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end-organ damage, often involving the kidneys. Complement-mediated hemolytic uremic syndrome (cHUS), a rare form of TMA, arises from dysregulated alternative complement pathway activation, frequently due to genetic mutations. We report the case of a 23-year-old male presenting with TMA secondary to a heterozygous mutation in the membrane cofactor protein (MCP/CD46) gene. The patient exhibited severe renal and cardiovascular complications, including acute kidney injury requiring hemodialysis, uremic pericarditis, and persistent anemia. Diagnostic evaluation confirmed complement dysregulation, and management with eculizumab, plasmapheresis, and hemodialysis was initiated. Renal biopsy revealed classic TMA features, and genetic testing identified the MCP mutation, underscoring the importance of genetic predispositions in guiding diagnosis and therapy. This case emphasizes the critical role of genetic testing in TMA evaluation and highlights the potential for improved outcomes through targeted complement inhibition and individualized care strategies. [ABSTRACT FROM AUTHOR]

Introduction: Sarcoidosis is a multisystem inflammatory disease of unknown etiology characterized by the formation of noncaseating epithelioid granulomas. Clinically significant renal involvement is rare in sarcoidosis. It most commonly manifests as chronic tubulointerstitial nephritis and nephrocalcinosis with nephrolithiasis. Further, glomerular involvement is observed sporadically, mainly membranous glomerulopathy or focal segmental glomerulosclerosis. Case presentation: We describe the clinical case of a 49-year-old patient of Caucasian ethnicity with a history of sarcoidosis of the lungs and intrathoracic lymph nodes who was hospitalized for acute kidney injury, hypercalcemia, hypoxemic respiratory insufficiency, general weakness, weight loss, and fever. Conservative treatment was not successful, and therefore early initiation of renal function replacement in the form of intermittent hemodialysis was necessary. During differential diagnosis process, we found nephrotic range proteinuria with microscopic hematuria; autoantibody panel was completely negative. Histologically, a unique constellation of renal lesions in the form of severe chronic tubulointerstitial nephritis combined with diffuse sclerosing crescentic glomerulonephritis was confirmed. Computed tomography scan of the lungs revealed recurrence of sarcoidosis, and a secondary finding was subpleurally localized primary calcified tuberculous infection. Treatment with corticosteroids was initiated in collaboration with a pulmonologist, with rapid improvement in the patient's extrarenal clinical condition. Conclusion: Sarcoidosis needs to be considered in the differential diagnosis of rapidly progressive glomerulonephritis even though it is a very rare type of renal involvement. [ABSTRACT FROM AUTHOR]

Background: Guidelines suggest treating fully penicillin-susceptible Enterococcus faecalis strains causing infective endocarditis with amoxicillin combined with gentamicin or ceftriaxone, but clinical evidence to support this practice is limited and monotherapy cohorts were excluded from studies. We describe antibiotic treatment, complications, and outcomes in patients with Enterococcus faecalis infective endocarditis, specifically comparing monotherapy versus combination therapy. Methods: Retrospective analysis of prospectively collected cohort of patients with definite or possible infective endocarditis from 2 English centres between 2006 and 2021. The primary outcome was 30-day mortality. Secondary outcomes included acute kidney injury, relapse, and clinical cure. Results: 178 individuals were included: median age was 72 years (interquartile range 60–79), male sex majority (138, 78%) and mostly native valve endocarditis (108, 61%). Thirty-nine patients (22%) received monotherapy (penicillin/glycopeptide/linezolid/daptomycin), 128 (72%) combination with gentamicin, 11 (6%) combination with ceftriaxone. Patients on combination therapy with gentamicin had a statistically significant lower 30-day mortality than those treated with monotherapy (21 (16.4%) versus 15 (38.5%) p = 0.035) and higher rates of clinical cure (101 (78.9%) versus 23 (59.0%) p = 0.018). Patient receiving gentamicin were more likely to experience acute kidney injury (64 (50%) versus 11 (28.2%) p = 0.057). Ceftriaxone combination was associated with poor outcomes, but the sample size was small. Conclusion: Patients treated with combination gentamicin therapy had better clinical outcomes than patients treated with monotherapy. Low-dose gentamicin regimens were associated with acute kidney injury. Patients treated with combinations were different to those treated with monotherapy and confounding remains a concern with observational analyses. An adequately powered clinical trial is needed to determine optimal treatment of enterococcal endocarditis. Clinical trial number: Not applicable. [ABSTRACT FROM AUTHOR]