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The document is a collection of summaries of various research studies related to HIV prevention and treatment. The studies cover a range of topics, including the use of pre-exposure prophylaxis (PrEP), the development of HIV vaccines and antibodies, and the implementation of long-acting HIV prevention methods. The studies provide valuable insights into different strategies and interventions aimed at increasing HIV testing, prevention, and treatment outcomes. The document is culturally sensitive and respectful of diverse perspectives, making it a useful resource for library patrons conducting research on specific HIV-related topics. [Extracted from the article]

(1) Background: Adequate organ perfusion during cardiopulmonary bypass (CPB) requires accurate estimation and adjustment of flow rates which conventional methods may not always achieve. Perioperative monitoring of cerebral oxygen saturation (ScO2) may detect changes in oxygen transport. This study aims to compare estimated and measured perfusion flow rates and assess the capacity of ScO2 to detect subtle changes in oxygen transport during CPB. (2) Methods: This observational study included 50 patients scheduled for elective coronary artery bypass grafting (CABG) surgery, all of whom provided written informed consent. Perfusion flow rates were estimated using the DuBois formula and measured using echocardiography and a flow probe in the arterial line of the CPB system. ScO2 was continuously monitored, alongside intermittent measurements of oxygen delivery and extraction ratios. (3) Results: Significant discrepancies were found between estimated flow rates (5.2 [4.8–5.5] L/min) and those measured at the start of the surgery (4.6 [4.0–5.0] L/min). These discrepancies were flow rate-dependent, being more pronounced at lower perfusion rates and diminishing as rates increased. Furthermore, ScO2 showed a consistent correlation with both oxygen delivery (r = 0.48) and oxygen extraction ratio (r = 0.45). (4) Conclusions: This study highlights discrepancies between estimated and actual perfusion flow rates during CPB and underscores the value of ScO2 monitoring as a continuous, noninvasive tool for maintaining adequate organ perfusion, suggesting a need for improved, patient-tailored perfusion strategies. [ABSTRACT FROM AUTHOR]

Genetic variants in the protein-coding regions of APOL1 are associated with an increased risk and progression of chronic kidney disease (CKD) in African Americans. Hypoxia exacerbates CKD progression by stabilizing HIF-1α, which induces APOL1 transcription in kidney podocytes. However, the contribution of additional mediators to regulating APOL1 expression under hypoxia in podocytes is unknown. Here, we report that a transient accumulation of HIF-1α in hypoxia is sufficient to upregulate APOL1 expression in podocytes through a cGAS/STING/IRF3-independent pathway. Notably, IFI16 ablation impedes hypoxia-driven APOL1 expression despite the nuclear accumulation of HIF-1α. Co-immunoprecipitation assays indicate no direct interaction between IFI16 and HIF-1α. Our studies identify hypoxia response elements (HREs) in the APOL1 gene enhancer/promoter region, showing increased HIF-1α binding to HREs located in the APOL1 gene enhancer. Luciferase reporter assays confirm the role of these HREs in transcriptional activation. Chromatin immunoprecipitation (ChIP)–qPCR assays demonstrate that IFI16 is not recruited to HREs, and IFI16 deletion reduces HIF-1α binding to APOL1 HREs. RT-qPCR analysis indicates that IFI16 selectively affects APOL1 expression, with a negligible impact on other hypoxia-responsive genes in podocytes. These findings highlight the unique contribution of IFI16 to hypoxia-driven APOL1 gene expression and suggest alternative IFI16-dependent mechanisms regulating APOL1 gene expression under hypoxic conditions. [ABSTRACT FROM AUTHOR]

Simple Summary: This review aims to characterize the unique presentation of renal cell carcinoma (RCC) in kidney transplant patients with end-stage kidney disease (ESKD). RCC in the ESKD patient is an ambiguous and under-studied area of oncology, as dialysis and transplantation alter the biological environment of the kidney. Assessing outcomes and dictating management for RCC in this anomalous patient population pose oncologic challenges, and thus warrant a review to update clinicians. The potential for donor tissue to cause cancer in the organ recipient is unknown, but one can assume that this risk is minimal. Our review challenges this concept and we propose new insights into how donor and recipient environments might influence the risk of cancer in the transplant recipient. Kidney transplant patients have a higher risk of renal cell carcinoma (RCC) compared to non-transplanted end-stage kidney disease (ESKD) patients. This increased risk has largely been associated with the use of immunosuppression; however, recent genetic research highlights the significance of tissue specificity in cancer driver genes. The implication of tissue specificity becomes more obscure when addressing transplant patients, as two distinct metabolic environments are present within one individual. The oncogenic potential of donor renal tissue is largely unknown but assumed to pose minimal risk to the kidney transplant recipient (KTR). Our review challenges this notion by examining how donor and recipient microenvironments impact a transplant recipient's associated risk of renal cell carcinoma. In doing so, we attempt to encapsulate how ESKD-RCC and KTR-RCC differ in their incidence, pathogenesis, outcome, and approach to management. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) affects up to 50% of cardiac surgery patients. The definition of AKI is based on changes in serum creatinine relative to a baseline measurement or a decrease in urine output. These monitoring methods lead to a delayed diagnosis. Monitoring the partial pressure of oxygen in urine (PuO2) may provide a method to assess the patient's AKI risk status dynamically. This study aimed to assess the predictive capability of two machine learning algorithms for AKI in cardiac surgery patients. One algorithm incorporated a feature derived from PuO2 monitoring, while the other algorithm solely relied on preoperative risk factors. The hypothesis was that the model incorporating PuO2 information would exhibit a higher area under the receiver operator characteristic curve (AUROC). An automated forward variable selection method was used to identify the best preoperative features. The AUROC for individual features derived from the PuO2 monitor was used to pick the single best PuO2-based feature. The AUROC for the preoperative plus PuO2 model vs. the preoperative-only model was 0.78 vs. 0.66 (p-value < 0.01). In summary, a model that includes an intraoperative PuO2 feature better predicts AKI than one that only includes preoperative patient data. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) associated with diabetes mellitus (DM) (known as diabetic kidney disease, DKD) is a serious and growing healthcare problem worldwide. In DM patients, DKD is generally diagnosed based on the presence of albuminuria and a reduced glomerular filtration rate. Diagnosis rarely includes an invasive kidney biopsy, although DKD has some characteristic histological features, and kidney fibrosis and nephron loss cause disease progression that eventually ends in kidney failure. Alternative sensitive and reliable non-invasive biomarkers are needed for DKD (and CKD in general) to improve timely diagnosis and aid disease monitoring without the need for a kidney biopsy. Such biomarkers may also serve as endpoints in clinical trials of new treatments. Non-invasive magnetic resonance imaging (MRI), particularly multiparametric MRI, may achieve these goals. In this article, we review emerging data on MRI techniques and their scientific, clinical, and economic value in DKD/CKD for diagnosis, assessment of disease pathogenesis and progression, and as potential biomarkers for clinical trial use that may also increase our understanding of the efficacy and mode(s) of action of potential DKD therapeutic interventions. We also consider how multi-site MRI studies are conducted and the challenges that should be addressed to increase wider application of MRI in DKD. [ABSTRACT FROM AUTHOR]

Biomarkers have become important tools in the diagnosis and management of cardiorenal syndrome (CRS), a complex condition characterized by dysfunction in both the cardiovascular and renal systems. Biomarkers can help identify the presence and severity of CRS, predict its progression and outcomes, and facilitate personalized treatment options. Several biomarkers, including natriuretic peptides, troponins, and inflammatory markers, have been extensively studied in CRS, and have shown promising results in improving diagnosis and prognosis. In addition, emerging biomarkers, such as kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin, offer potential for early detection and intervention of CRS. However, the use of biomarkers in CRS is still in its infancy, and further research is needed to establish their utility in routine clinical practice. This review highlights the role of biomarkers in the diagnosis, prognosis, and management of CRS, and discusses their potential as valuable clinical tools for personalized medicine in the future. [ABSTRACT FROM AUTHOR]

High-altitude environments dramatically influenced the genetic evolution of vertebrates. However, little is known about the role of RNA editing on high-altitude adaptation in non-model species. Here, we profiled the RNA editing sites (RESs) of heart, lung, kidney, and longissimus dorsi muscle from Tibetan cashmere goats (TBG, 4500 m) and Inner Mongolia cashmere goats (IMG, 1200 m) to reveal RNA editing-related functions of high-altitude adaptation in goats. We identified 84,132 high-quality RESs that were unevenly distributed across the autosomes in TBG and IMG, and more than half of the 10,842 non-redundant editing sites were clustered. The majority (62.61%) were adenosine-to-inosine (A-to-I) sites, followed by cytidine-to-uridine (C-to-U) sites (19.26%), and 32.5% of them had a significant correlation with the expression of catalytic genes. Moreover, A-to-I and C-to-U RNA editing sites had different flanking sequences, amino acid mutations, and alternative splicing activity. TBG had higher editing levels of A-to-I and C-to-U than IMG in the kidney, whereas a lower level was found in the longissimus dorsi muscle. Furthermore, we identified 29 IMG and 41 TBG population-specific editing sites (pSESs) and 53 population-differential editing sites (pDESs) that were functionally involved in altering RNA splicing or recoding protein products. It is worth noting that 73.3% population-differential, 73.2% TBG-specific, and 80% IMG-specific A-to-I sites were nonsynonymous sites. Moreover, the pSESs and pDESs editing-related genes play critical functions in energy metabolisms such as ATP binding molecular function, translation, and adaptive immune response, which may be linked to goat high-altitude adaptation. Our results provide valuable information for understanding the adaptive evolution of goats and studying plateau-related diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Acute kidney injury can result from multiple factors. The main cause is reduced renal perfusion. Kidneys are susceptible to ischemia due to the anatomy of microcirculation that wraps around the renal tubules. In the kidney, cortical and medullary superficial tubules have a large share in transport and require the supply of oxygen for energy production, while it is the cortex that receives almost 100% of the blood flowing through the kidneys and the medulla only accounts for 5–10% of it. This difference makes the tubules present in the superficial layer of the medulla very susceptible to ischemia. Impaired blood flow causes damage to the inner layer of vessels and thrombosis. The next stage is the disintegration of these vessels. The phenomenon of destruction of small vessels is called peritubular rarefaction, attributed as the main cause of further irreversible changes in the damaged kidney leading to the development of chronic kidney disease. In this article, we will present the characteristic structure of renal microcirculation, its regulation, and the mechanism of damage in acute ischemia, and we will try to find methods of prevention with particular emphasis on the inhibition of the renin–angiotensin–aldosterone system. Acute kidney injury (AKI) can result from multiple factors. The main cause is reduced renal perfusion. Kidneys are susceptible to ischemia due to the anatomy of microcirculation that wraps around the renal tubules–peritubular capillary (PTC) network. Cortical and medullary superficial tubules have a large share in transport and require the supply of oxygen for ATP production, while it is the cortex that receives almost 100% of the blood flowing through the kidneys and the medulla only accounts for 5–10% of it. This difference makes the tubules present in the superficial layer of the medulla very susceptible to ischemia. Impaired blood flow causes damage to the endothelium, with an increase in its prothrombotic and pro-adhesive properties. This causes congestion in the microcirculation of the renal medulla. The next stage is the migration of pericytes with the disintegration of these vessels. The phenomenon of destruction of small vessels is called peritubular rarefaction, attributed as the main cause of further irreversible changes in the damaged kidney leading to the development of chronic kidney disease. In this article, we will present the characteristic structure of renal microcirculation, its regulation, and the mechanism of damage in acute ischemia, and we will try to find methods of prevention with particular emphasis on the inhibition of the renin–angiotensin–aldosterone system. [ABSTRACT FROM AUTHOR]

Partial pressure of oxygen (pO2) in the kidney is maintained at a relatively stable level by a unique and complex functional interplay between renal blood flow, glomerular filtration rate (GFR), oxygen consumption, and arteriovenous oxygen shunting. The vulnerability of this interaction renders the kidney vulnerable to hypoxic injury, leading to different renal diseases. Hypoxia has long been recognized as an important factor in the pathogenesis of acute kidney injury (AKI), especially renal ischemia/reperfusion injury. Accumulating evidence suggests that hypoxia also plays an important role in the pathogenesis and progression of chronic kidney disease (CKD) and CKD-related complications, such as anemia, cardiovascular events, and sarcopenia. In addition, renal cancer is linked to the deregulation of hypoxia pathways. Renal cancer utilizes various molecular pathways to respond and adapt to changes in renal oxygenation. Particularly, hypoxia-inducible factor (HIF) (including HIF-1, 2, 3) has been shown to be activated in renal disease and plays a major role in the protective response to hypoxia. HIF-1 is a heterodimer that is composed of an oxygen-regulated HIF-1α subunit and a constitutively expressed HIF-1β subunit. In renal diseases, the critical characteristic of HIF-1α is protective, but it also has a negative effect, such as in sarcopenia. This review summarizes the mechanisms of HIF-1α regulation in renal disease. [ABSTRACT FROM AUTHOR]

The Kidney Disease Improving Global Outcomes (KDIGO) guidelines are currently used in acute kidney injury (AKI) diagnosis and include both serum creatinine (SCR) and urine output (UO) criteria. Currently, many AKI-related studies have inconsistently defined AKI, which possibly affects the comparison of their results. Therefore, we hypothesized that the different criteria in the KDIGO guidelines vary in measuring the incidence of AKI and its association with clinical outcomes. We retrospectively analyzed that data of patients admitted to the intensive care unit after non-cardiac surgery in 2019. Three different criteria used to define AKI were included: UOmean, mean UO < 0.5 mL/kg/h over time; UOcont, hourly UO < 0.5 mL/kg/h over time; or SCR, KDIGO guidelines SCR criteria. A total of 777 patients were included, and the incidence of UOmean-AKI was 33.1%, the incidence of UOcont-AKI was 7.9%, and the incidence of SCR-AKI was 2.0%. There were differences in the length of ICU stay and hospital stay between AKI and non-AKI patients under different criteria. We found differences in the incidence and clinical outcomes of AKI after non-cardiac surgery when using different KDIGO criteria. [ABSTRACT FROM AUTHOR]

The goal of this study was to analyze trends in the geometric parameters of blood vessels with age in a randomly selected group of 200 computed tomography angiography studies of radiologically healthy individuals using dedicated statistical techniques. A quantitative description of cerebral vascular geometry with numerical parameters (bifurcation angle, branching angle, co‐planarity index, average curvature, and average torsion) was proposed. The changes and variability in geometry were analyzed according to age. The bifurcation angle, branching angle, and average curvature increased with age, whereas the co‐planarity index and average torsion decreased with age. For equal‐diameter branches, women comparing to men presented lower bifurcation angles in the 4th decade of life, and lower values for the co‐planarity index in the 3rd and 4th decades of life. In non–equal‐diameter branches, the opposite relationship was observed for bifurcation angle in the 4th decade of life comparing both groups. All analyzed parameters showed clearly visible trends with patient age. Deviations in specific decades of life were detected; these deviations could be linked to the development of aneurysms in specific age groups. [ABSTRACT FROM AUTHOR]

Renal tissue hypoperfusion and hypoxia are key elements in the pathophysiology of acute kidney injury and its progression to chronic kidney disease. Yet, in vivo assessment of renal haemodynamics and tissue oxygenation remains a challenge. Many of the established approaches are invasive, hence not applicable in humans. Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) offers an alternative. BOLD-MRI is non-invasive and indicative of renal tissue oxygenation. Nonetheless, recent (pre-) clinical studies revived the question as to how bold renal BOLD-MRI really is. This review aimed to deliver some answers. It is designed to inspire the renal physiology, nephrology and imaging communities to foster explorations into the assessment of renal oxygenation and haemodynamics by exploiting the powers of MRI. For this purpose, the specifics of renal oxygenation and perfusion are outlined. The fundamentals of BOLD-MRI are summarized. The link between tissue oxygenation and the oxygenation-sensitive MR biomarker [ABSTRACT FROM AUTHOR]

In this review encouraged by original data, we first provided in vivo evidence that the kidney, comparative to the liver or brain, is an organ particularly rich in cysteine. In the kidney, the total availability of cysteine was higher in cortex tissue than in the medulla and distributed in free reduced, free oxidized and protein-bound fractions (in descending order). Next, we provided a comprehensive integrated review on the evidence that supports the reliance on cysteine of the kidney beyond cysteine antioxidant properties, highlighting the relevance of cysteine and its renal metabolism in the control of cysteine excess in the body as a pivotal source of metabolites to kidney biomass and bioenergetics and a promoter of adaptive responses to stressors. This view might translate into novel perspectives on the mechanisms of kidney function and blood pressure regulation and on clinical implications of the cysteine-related thiolome as a tool in precision medicine. [ABSTRACT FROM AUTHOR]

Acute kidney injury of various origins shares a common link in the pathophysiological chain of events: imbalance between renal medullary oxygen delivery and oxygen demand. For in vivo assessment of kidney haemodynamics and oxygenation in animals, quantitative but invasive physiological methods are established. A very limited number of studies attempted to link these invasive methods with parametric Magnetic Resonance Imaging ( MRI) of the kidney. Moreover, the validity of parametric MRI ( pMRI) as a surrogate marker for renal tissue perfusion and renal oxygenation has not been systematically examined yet. For this reason, we set out to combine invasive techniques and non-invasive MRI in an integrated hybrid setup ( MR- PHYSIOL) with the ultimate goal to calibrate, monitor and interpret parametric MR and physiological parameters by means of standardized interventions. Here we present a first report on the current status of this multi-modality approach. For this purpose, we first highlight key characteristics of renal perfusion and oxygenation. Second, concepts for in vivo characterization of renal perfusion and oxygenation are surveyed together with the capabilities of MRI for probing blood oxygenation-dependent tissue stages. Practical concerns evoked by the use of strong magnetic fields in MRI and interferences between MRI and invasive physiological probes are discussed. Technical solutions that balance the needs of in vivo physiological measurements together with the constraints dictated by small bore MR scanners are presented. An early implementation of the integrated MR- PHYSIOL approach is demonstrated including brief interventions of hypoxia and hyperoxia. [ABSTRACT FROM AUTHOR]

Renal failure is a major health problem that is increasing worldwide. To improve clinical outcomes, we need to understand the basic mechanisms of kidney disease. Aging is a risk factor for the development and progression of kidney disease. Cells develop an imbalance of oxidants and antioxidants as they age, resulting in oxidative stress and the development of kidney damage. Calorie restriction (CR) is recognized as a dietary approach that promotes longevity, reduces oxidative stress, and delays the onset of age-related diseases. Sirtuins, a type of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase, are considered to be anti-aging molecules, and CR induces their expression. The sirtuin family consists of seven enzymes (Sirt1–7) that are involved in processes and functions related to antioxidant and oxidative stress, such as DNA damage repair and metabolism through histone and protein deacetylation. In fact, a role for sirtuins in the regulation of antioxidants and redox substances has been suggested. Therefore, the activation of sirtuins in the kidney may represent a novel therapeutic strategy to enhancing resistance to many causative factors in kidney disease through the reduction of oxidative stress. In this review, we discuss the relationship between sirtuins and oxidative stress in renal disease. [ABSTRACT FROM AUTHOR]

The renal fibrotic process is characterized by a chronic inflammatory state and oxidative stress. Antirhea borbonica (A. borbonica) is a French medicinal plant found in Reunion Island and known for its antioxidant and anti-inflammatory activities mostly related to its high polyphenols content. We investigated whether oral administration of polyphenol-rich extract from A. borbonica could exert in vivo a curative anti-renal fibrosis effect. To this aim, three days after unilateral ureteral obstruction (UUO), mice were daily orally treated either with a non-toxic dose of polyphenol-rich extract from A. borbonica or with caffeic acid (CA) for 5 days. The polyphenol-rich extract from A. borbonica, as well as CA, the predominant phenolic acid of this medicinal plant, exerted a nephroprotective effect through the reduction in the three phases of the fibrotic process: (i) macrophage infiltration, (ii) myofibroblast appearance and (iii) extracellular matrix accumulation. These effects were associated with the mRNA down-regulation of Tgf-β, Tnf-α, Mcp1 and NfkB, as well as the upregulation of Nrf2. Importantly, we observed an increased antioxidant enzyme activity for GPX and Cu/ZnSOD. Last but not least, desorption electrospray ionization-high resolution/mass spectrometry (DESI-HR/MS) imaging allowed us to visualize, for the first time, CA in the kidney tissue. The present study demonstrates that polyphenol-rich extract from A. borbonica significantly improves, in a curative way, renal tubulointerstitial fibrosis progression in the UUO mouse model. [ABSTRACT FROM AUTHOR]

The foaming of geopolymers lowers their density, thus opening up new environmental benefits, including acoustic and thermal insulation. At the same time, foaming disturbs the homogeneity of the material, which worsens the strength parameters, and particularly those related to tension, which can be improved by introducing reinforcement. This paper presents the results of research on foamed geopolymers reinforced with glass fiber meshes, a type of reinforcement that provides an adequate bond. The samples tested here were based on three types of coal fly ash, and were foamed with varying doses of hydrogen peroxide. Samples were cured at 40 °C and were tested after 28 days of maturing at ambient temperature. The strength parameters of the synthesized geopolymers were determined via laboratory testing, and were used to evaluate load-bearing capacity models of the tested samples reinforced with glass fiber mesh. The results showed the importance of the type of ash on the strength properties and efficiency of reinforcement. At the same time, a slight deterioration in the glass fibers was noticed; this was caused by the presence of sodium hydroxide solution, which was used as an activator. [ABSTRACT FROM AUTHOR]

The development of sustainable, environmentally friendly insulation materials with a reduced carbon footprint is attracting increased interest. One alternative to conventional insulation materials are foamed geopolymers. Similar to foamed concrete, the mechanical properties of geopolymer foams can also be improved by using fibers for reinforcement. This paper presents an overview of the latest research findings in the field of fiber-reinforced geopolymer foam concrete with special focus on natural fibers reinforcement. Furthermore, some basic and background information of natural fibers and geopolymer foams are reported. In most of the research, foams are produced either through chemical foaming with hydrogen peroxide or aluminum powder, or through mechanical foaming which includes a foaming agent. However, previous reviews have not sufficiently addresses the fabrication of geopolymer foams by syntactic foams. Finally, recent efforts to reduce the fiber degradation in geopolymer concrete are discussed along with challenges for natural fiber reinforced-geopolymer foam concrete. [ABSTRACT FROM AUTHOR]

(1) Background: There are no successive treatments for heart failure with preserved ejection fraction (HFpEF) because of complex interactions between environmental, histological, and genetic risk factors. The objective of the study is to investigate changes in cardiomyocytes and molecular networks associated with HFpEF. (2) Methods: Dahl salt-sensitive (DSS) rats developed HFpEF when fed with a high-salt (HS) diet for 7 weeks, which was confirmed by in vivo and ex vivo measurements. Shotgun proteomics, microarray, Western blot, and quantitative RT-PCR analyses were further carried out to investigate cellular and molecular mechanisms. (3) Results: Rats with HFpEF showed diastolic dysfunction, impaired systolic function, and prolonged repolarization of myocytes, owing to an increase in cell size and apoptosis of myocytes. Heatmap of multi-omics further showed significant differences between rats with HFpEF and controls. Gene Set Enrichment Analysis (GSEA) of multi-omics revealed genetic risk factors involved in cardiac muscle contraction, proteasome, B cell receptor signaling, and p53 signaling pathway. Gene Ontology (GO) analysis of multi-omics showed the inflammatory response and mitochondrial fission as top biological processes that may deteriorate myocyte stiffening. GO analysis of protein-to-protein network indicated cytoskeleton protein, cell fraction, enzyme binding, and ATP binding as the top enriched molecular functions. Western blot validated upregulated Mff and Itga9 and downregulated Map1lc3a in the HS group, which likely contributed to accumulation of aberrant mitochondria to increase ROS and elevation of myocyte stiffness, and subsequent contractile dysfunction and myocardial apoptosis. (4) Conclusions: Multi-omics analysis revealed multiple pathways associated with HFpEF. This study shows insight into molecular mechanisms for the development of HFpEF and may provide potential targets for the treatment of HFpEF. [ABSTRACT FROM AUTHOR]

Although intraoperative hemodynamic variables were reported to be associated with acute kidney injury (AKI) after liver transplantation, the time-dependent association between intraoperative oxygen delivery and AKI has not yet been evaluated. We reviewed 676 cases of liver transplantation. Oxygen delivery index (DO2I) was calculated at least ten times during surgery. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria. The area under the curve (AUC) was calculated as below a DO2I of 300 (AUC < 300), 400 and 500 mL/min/m2 threshold. Also, the cumulative time below a DO2I of 300 (Time < 300), 400, and 500 mL/min/m2 were calculated. Multivariable logistic regression analysis was performed to evaluate whether AUC < 300 or time < 300 was independently associated with the risk of AKI. As a sensitivity analysis, propensity score matching analysis was performed between the two intraoperative mean DO2I groups using a cutoff of 500 mL/min/m2, and the incidence of AKI was compared between the groups. Multivariable analysis showed that AUC < 300 or time < 300 was an independent predictor of AKI (AUC < 300: odds ratio [OR] = 1.10, 95% confidence interval [CI] 1.06–1.13, time < 300: OR = 1.10, 95% CI 1.08–1.14). Propensity score matching yielded 192 pairs of low and high mean DO2I groups. The incidence of overall and stage 2 or 3 AKI was significantly higher in the lower DO2I group compared to the higher group (overall AKI: lower group, n = 64 (33.3%) vs. higher group, n = 106 (55.2%), p < 0.001). In conclusion, there was a significant time-dependent association between the intraoperative poor oxygen delivery < 300 mL/min/m2 and the risk of AKI after liver transplantation. The intraoperative optimization of oxygen delivery may mitigate the risk of AKI. [ABSTRACT FROM AUTHOR]

The renal cortex drives renal function. Hypoxia/reoxygenation are primary factors in ischemia-reperfusion (IR) injuries, but renal oxygenation per se is complex and awaits full elucidation. Few mathematical models address this issue: none captures cortical tissue heterogeneity. Using agent-based modeling, we develop the first model of cortical oxygenation at the cell-tissue level (RCM), based on first principles and careful bibliographical analysis. Entirely parameterized with Rat data, RCM is a morphometrically equivalent 2D-slice of cortical tissue, featuring peritubular capillaries (PTC), tubules and interstitium. It implements hemoglobin/O2 binding-release, oxygen diffusion, and consumption, as well as capillary and tubular flows. Inputs are renal blood flow RBF and PO2 feeds; output is average tissue PO2 (tPO2). After verification and sensitivity analysis, RCM was validated at steady-state (tPO2 37.7 ± 2.2 vs. 36.9 ± 6 mmHg) and under transients (ischemic oxygen half-time: 4.5 ± 2.5 vs. 2.3 ± 0.5 s in situ). Simulations confirm that PO2 is largely independent of RBF, except at low values. They suggest that, at least in the proximal tubule, the luminal flow dominantly contributes to oxygen delivery, while the contribution of capillaries increases under partial ischemia. Before addressing IR-induced injuries, upcoming developments include ATP production, adaptation to minutes–hours scale, and segmental and regional specification. [ABSTRACT FROM AUTHOR]

The outcome of patients with acute myocardial infarction (AMI) has dramatically improved over recent decades, thanks to early detection and prompt interventions to restore coronary blood flow. In contrast, the prognosis of patients with hypoxic acute kidney injury (AKI) remained unchanged over the years. Delayed diagnosis of AKI is a major reason for this discrepancy, reflecting the lack of symptoms and diagnostic tools indicating at real time altered renal microcirculation, oxygenation, functional derangement and tissue injury. New tools addressing these deficiencies, such as biomarkers of tissue damage are yet far less distinctive than myocardial biomarkers and advanced functional renal imaging technologies are non-available in the clinical practice. Moreover, our understanding of pathogenic mechanisms likely suffers from conceptual errors, generated by the extensive use of the wrong animal model, namely warm ischemia and reperfusion. This model parallels mechanistically type I AMI, which properly represents the rare conditions leading to renal infarcts, whereas common scenarios leading to hypoxic AKI parallel physiologically type II AMI, with tissue hypoxic damage generated by altered oxygen supply/demand equilibrium. Better understanding the pathogenesis of hypoxic AKI and its management requires a more extensive use of models of type II-rather than type I hypoxic AKI. [ABSTRACT FROM AUTHOR]