Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting.

Patients with cirrhosis are prone to developing acute kidney injury (AKI), a complication associated with a markedly increased in-hospital morbidity and mortality, along with a risk of progression to chronic kidney disease. Whereas patients with cirrhosis are at increased risk of developing any phenotype of AKI, hepatorenal syndrome (HRS), a specific form of AKI (HRS-AKI) in patients with advanced cirrhosis and ascites, carries an especially high mortality risk. Early recognition of HRS-AKI is crucial since administration of splanchnic vasoconstrictors may reverse the AKI and serve as a bridge to liver transplantation, the only curative option. In 2023, a joint meeting of the International Club of Ascites (ICA) and the Acute Disease Quality Initiative (ADQI) was convened to develop new diagnostic criteria for HRS-AKI, to provide graded recommendations for the work-up, management and post-discharge follow-up of patients with cirrhosis and AKI, and to highlight priorities for further research.

Development of a new miniaturized system for ultrafiltration.

Acute decompensated heart failure and fluid overload are the most common causes of hospitalization in heart failure patients, and often, they contribute to disease progression. Initial treatment encompasses intravenous diuretics although there might be a percentual of patients refractory to this pharmacological approach. New technologies have been developed to perform extracorporeal ultrafiltration in fluid overloaded patients. Current equipment allows to perform ultrafiltration in most hospital and acute care settings. Extracorporeal ultrafiltration is then prescribed and conducted by specialized teams, and fluid removal is planned to restore a status of hydration close to normal. Recent clinical trials and European and North American practice guidelines suggest that ultrafiltration is indicated for patients with refractory congestion not responding to medical therapy. Close interaction between nephrologists and cardiologists may be the key to a collaborative therapeutic effort in heart failure patients. Further studies are today suggesting that wearable technologies might become available soon to treat patients in ambulatory and de-hospitalized settings. These new technologies may help to cope with the increasing demand for the care of chronic heart failure patients. Herein, we provide a state-of-the-art review on extracorporeal ultrafiltration and describe the steps in the development of a new miniaturized system for ultrafiltration, called AD1 (Artificial Diuresis).

Oxidative stress, defective proteostasis and immunometabolic complications in critically ill patients.

Oxidative stress (OS) develops in critically ill patients as a metabolic consequence of the immunoinflammatory and degenerative processes of the tissues. These induce increased and/or dysregulated fluxes of reactive species enhancing their pro-oxidant activity and toxicity. At the same time, OS sustains its own inflammatory and immunometabolic pathogenesis, leading to a pervasive and vitious cycle of events that contribute to defective immunity, organ dysfunction and poor prognosis. Protein damage is a key player of these OS effects; it generates increased levels of protein oxidation products and misfolded proteins in both the cellular and extracellular environment, and contributes to forms DAMPs and other proteinaceous material to be removed by endocytosis and proteostasis processes of different cell types, as endothelial cells, tissue resident monocytes-macrophages and peripheral immune cells. An excess of OS and protein damage in critical illness can overwhelm such cellular processes ultimately interfering with systemic proteostasis, and consequently with innate immunity and cell death pathways of the tissues thus sustaining organ dysfunction mechanisms. Extracorporeal therapies based on biocompatible/bioactive membranes and new adsorption techniques may hold some potential in reducing the impact of OS on the defective proteostasis of patients with critical illness. These can help neutralizing reactive and toxic species, also removing solutes in a wide spectrum of molecular weights thus improving proteostasis and its immunometabolic corelates. Pharmacological therapy is also moving steps forward which could help to enhance the efficacy of extracorporeal treatments. This narrative review article explores the aspects behind the origin and pathogenic role of OS in intensive care and critically ill patients, with a focus on protein damage as a cause of impaired systemic proteostasis and immune dysfunction in critical illness.

Hemoadsorption: Consensus report of the 30th Acute Disease Quality Initiative workgroup.

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex-vivo, experimental, and clinical observations. Accordingly, unspecific adsorptive extracorporeal therapies have now been applied to the treatment of a wide array of conditions from poisoning to drug overdoses, to inflammatory states and sepsis, and acute or chronic liver and kidney failure. In response to the rapidly expanding knowledge base and increased clinical evidence, we convened an Acute Disease Quality Initiative (ADQI) consensus conference dedicated to such treatment. The data show that hemoadsorption has clinically acceptable short-term biocompatibility and safety, technical feasibility, and experimental demonstration of specified target molecule removal. Pilot studies demonstrate potentially beneficial effects on physiology and larger studies of endotoxin-based hemoadsorption have identified possible target phenotypes for larger randomized controlled trials (RCTs). Moreover, in a variety of endogenous and exogenous intoxications, removal of target molecules has been confirmed in vivo. However, some studies have raised concerns about harm or failed to deliver benefits. Thus, despite many achievements, modern hemoadsorption remains a novel and experimental intervention with limited data, and a large research agenda.

Postoperative Fluid Accumulation is Associated With Underestimation of AKI Severity in Lung Transplant Recipients.

BACKGROUND: Post-lung transplantation (LTx) fluid accumulation can lead to dilution of serum creatinine (SCr). We hypothesized that fluid accumulation might impact the diagnosis, staging, and outcome of posttransplant acute kidney injury (AKI). METHODS: In this retrospective study, we analyzed data from 131 adult LTx patients at a single German lung center between 2005 and 2018. We assessed the occurrence of AKI within 7 days posttransplant, both before and after SCr-adjustment for fluid balance (FB), and investigated its impact on all-cause mortality. Transient and persistent AKIs were defined as return to baseline kidney function or continuation of AKI beyond 72 h of onset, respectively. RESULTS: AKI was diagnosed in 58.8% of patients according to crude SCr values. When considering FB-adjusted SCr values, AKI severity was underestimated in 20.6% of patients, that is, AKI was detected in an additional 6.9% of patients and led to AKI upstaging in 23.4% of cases. Patients initially underestimated but detected with AKI only after FB adjustment had higher mortality compared to those who did not meet AKI criteria (hazard ratio [HR] 2.98; 95% confidence interval [CI] 1.06, 8.36; p = 0.038). Persistent AKI was associated with higher mortality than transient AKI, regardless of using crude or adjusted SCr values (p < 0.05). Persistent AKI emerged as an independent risk factor for mortality (HR 2.35; 95% CI 1.29, 4.30; p = 0.005). CONCLUSION: Adjusting for FB and evaluating renal recovery patterns post-AKI may enhance the sensitivity of AKI detection. This approach could help identify patients with poor prognosis and potentially improve outcomes in lung transplant recipients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03039959, NCT03046277.

Pediatric AKI in the real world: changing outcomes through education and advocacy-a report from the 26th Acute Disease Quality Initiative (ADQI) consensus conference.

BACKGROUND: Acute kidney injury (AKI) is independently associated with increased morbidity and mortality across the life course, yet care for AKI remains mostly supportive. Raising awareness of this life-threatening clinical syndrome through education and advocacy efforts is the key to improving patient outcomes. Here, we describe the unique roles education and advocacy play in the care of children with AKI, discuss the importance of customizing educational outreach efforts to individual groups and contexts, and highlight the opportunities created through innovations and partnerships to optimize lifelong health outcomes. METHODS: During the 26th Acute Disease Quality Initiative (ADQI) consensus conference, a multidisciplinary group of experts discussed the evidence and used a modified Delphi process to achieve consensus on recommendations on AKI research, education, practice, and advocacy in children. RESULTS: The consensus statements developed in response to three critical questions about the role of education and advocacy in pediatric AKI care are presented here along with a summary of available evidence and recommendations for both clinical care and research. CONCLUSIONS: These consensus statements emphasize that high-quality care for patients with AKI begins in the community with education and awareness campaigns to identify those at risk for AKI. Education is the key across all healthcare and non-healthcare settings to enhance early diagnosis and develop mitigation strategies, thereby improving outcomes for children with AKI. Strong advocacy efforts are essential for implementing these programs and building critical collaborations across all stakeholders and settings.

Sorbent functionalization with vancomycin enhances bacteria killing in extracorporeal hemoadsorption.

BACKGROUND: The level of bacteremia in patients with sepsis and septic shock is a predictor of complications and mortality, regardless of the type of bacteria. Devices for bacteria, endotoxin and cytokines removal by adsorption have been recently developed. Thus, extracorporeal blood purification therapies have been proposed as adjunctive therapy in sepsis in combination with drugs. Some potentially useful drugs, however, are precluded due to their organ or metabolic toxicity. The present study represents a preliminary report on the in vitro effect of a sorbent device (minimodule with HA380 beads, Jafron medical, Zhuhai, China) in which the particles have been functionalized with vancomycin on the surface. The impact of the surface-modified beads on circulating bacteria (Staphylococcus aureus) has been tested in a simulated in vitro circulation. METHODS: In vitro experiments were carried out with 800 mL of blood enriched with S. aureus species. Blood was circulated in the vancomycin-functionalized and non-functionalized mini-module cartridges in hemoadsorption setup (300 mL each) and the bactericidal effect was assessed. Also, 200 mL of blood was used as a control. RESULTS: A significant increase in the time to positivity of blood cultures was observed after 60 min and also after 120 min of therapy with the mini-module functionalized with vancomycin as opposed to the non-functionalized cartridge. CONCLUSIONS: These results suggest a possible way of treating sepsis by using drug- or antibiotic-functionalized cartridges without worrying about pharmacological toxicity. The prolongation of the time to bacterial culture positivity to S. aureus after a passage through a column packed with beads functionalized with vancomycin represents a proof of concept.

Ultrafiltration Tolerance: A Phenotype That We Need to Recognize.

BACKGROUND: The evaluation and management of fluid balance are key challenges in critical care patients who require renal replacement therapies because cumulative fluid balance is an independent factor that increases morbidity and mortality in different clinical scenarios. SUMMARY: One of the strategies when fluid overload is refractory to diuretics is extracorporeal fluid removal (i.e., net ultrafiltration [UFNET] during kidney replacement therapy). However, problems with UFNET without individualized assessment are cardiovascular events and intradialytic hypotension, events that contribute to decreasing organ perfusion and sympathetic stress. Therefore, we must consider and try to predict the best timing for the start of ultrafiltration and find the point where the patient is most tolerant to ultrafiltration, making a simile to the concept of fluid tolerance. KEY MESSAGES: UFNET is a continuous and dynamic process, going through moments of tolerance and intolerance to ultrafiltration; as nephrologists, we must take the necessary measures to move through this period.

Generative AI in Critical Care Nephrology: Applications and Future Prospects.

BACKGROUND: Generative artificial intelligence (AI) is rapidly transforming various aspects of healthcare, including critical care nephrology. Large language models (LLMs), a key technology in generative AI, show promise in enhancing patient care, streamlining workflows, and advancing research in this field. SUMMARY: This review analyzes the current applications and future prospects of generative AI in critical care nephrology. Recent studies demonstrate the capabilities of LLMs in diagnostic accuracy, clinical reasoning, and continuous renal replacement therapy (CRRT) alarm troubleshooting. As we enter an era of multiagent models and automation, the integration of generative AI into critical care nephrology holds promise for improving patient care, optimizing clinical processes, and accelerating research. However, careful consideration of ethical implications and continued refinement of these technologies are essential for their responsible implementation in clinical practice. This review explores the current and potential applications of generative AI in nephrology, focusing on clinical decision support, patient education, research, and medical education. Additionally, we examine the challenges and limitations of AI implementation, such as privacy concerns, potential bias, and the necessity for human oversight. KEY MESSAGES: (i) LLMs have shown potential in enhancing diagnostic accuracy, clinical reasoning, and CRRT alarm troubleshooting in critical care nephrology. (ii) Generative AI offers promising applications in patient education, literature review, and academic writing within the field of nephrology. (iii) The integration of AI into electronic health records and clinical workflows presents both opportunities and challenges for improving patient care and research. (iv) Addressing ethical concerns, ensuring data privacy, and maintaining human oversight are crucial for the responsible implementation of AI in critical care nephrology.

Human Proenkephalin A 119-159 (penKid) in Extracorporeal Therapies: Ex vivo Sieving Coefficient, Diffusive Clearance, and Hemoadsorption Kinetics.

INTRODUCTION: Enkephalins, endogenous opioid peptides, are involved in the regulation of renal function. One derived molecule, proenkephalin A, also known as penKid, has been demonstrated to be a reliable biomarker for kidney function and its plasma concentration correlates with measured glomerular filtration rate. penKid is used for prediction and diagnosis of AKI and need of renal replacement therapy (RRT). penKid has also been used to predict the successful weaning from RRT in patients with AKI. Whether the concentration of penKid is affected or not by RRT is a controversial point and there are no studies describing the kinetics of the molecule in such conditions. The low molecular weight (4.5 kDa) would imply free removal by the glomerulus and the dialysis membranes. During RRT, this reduction could not be detected in clinical practice due to the complex kinetics involving either low dialytic clearance or increased production in response to impaired kidney function. The aim of this study was to determine the sieving coefficient and the diffusive clearance of the penKid molecule in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively, and also the penKid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous resin. METHODS: Blood spiked with a lyophilized penKid peptide solved in 20 mm dipotassium phosphate and 6 mm disodium EDTA [pH 8] to reach target concentrations is used as testing solution. In each experiment, the blood batch was adjusted at a volume of 1,000 mL, maintained at 37°, and continuously stirred. Samples were collected from blood, ultrafiltrate, and spent dialysate at different times during the experiments. Sieving, clearance, and removal ratio were calculated. RESULTS: Significant removal of penKid was observed in CVVH (sieving 1.04 ± 0.27), in CVVHD (clearance 23.08 ± 0.89), and in HA (removal ratio 76.1 ± 1% after 120 min). CONCLUSION: penKid is effectively removed by extracorporeal therapies. In presence of anuria, penKid generation kinetics can be calculated based on extracorporeal removal and volume variation. In steady state conditions, declining values may be the result of an initial renal function recovery and may suggest discontinuation and successful liberation from RRT.

Effect of Mechanical Vibration on Kinetics of Solute Adsorption.

INTRODUCTION: Hemadsorption with new sorbent cartridges is an emerging extracorporeal blood purification technique. Flow distribution inside the sorbent is one of the main issues concerning the device's performance and optimal sorbent utilization. In this experiment, we aimed to investigate the efficacy of vibration during adsorption by measuring the removal of vancomycin. METHODS: In this experimental study, 1,000 mL of saline with 10 g of vancomycin was circulated in a closed circuit (set flow of 250 mL/min) simulating a hemadsorption blood run using HA380 minimodule cartridge containing 75 g of wet resin. This vibration model was implemented with a damping head device installed in front of the adsorption cartridge during the experiment. The kinetics of the vancomycin were assessed by removal ratio over 120 min. RESULTS: We found no difference between the two models. Adsorption with and without vibration did not differ significantly for partial reduction ratios, overall amount of adsorbed molecule, or adsorption kinetics. CONCLUSION: The current design and structure of the minimodule cartridge demonstrated no difference in small-middle solute removal. Further improvement with the addition of mechanical vibration to the device was not observed.

Extracorporeal Removal of Per- and Polyfluoroalkyl Substances by Hemoadsorption: In vitro Kinetic Model.

INTRODUCTION: Per- and polyfluoroalkyl substances (PFAS) are known water pollutants leading to potential public health consequences. High blood levels of PFAS have been associated with several pathological conditions including testicular and kidney cancer. Classic extracorporeal therapies have demonstrated limited efficiency, and new approaches should be explored. In this study, we studied the possible role of hemoadsorption to achieve a fast, safe, and effective removal of PFAS from blood in patients with high blood levels. METHODS: We developed an in vitro model of hemoadsorption to test the potential of PFAS removal by extracorporeal treatment. We recirculated a highly polluted batch of water (4 L) through a sorbent cartridge (Jafron Medical, Zhuhai, China) for 120 min at a flow of 150 mL/min. We collected samples at different time points and analyzed 39 different PFAS compounds. RESULTS: For the PFAS compounds with concentrations significantly above normal, we observed a removal ratio close to 90% already within the first 60 min of circulation leading to almost complete elimination of all pollutants at 120 min. CONCLUSIONS: The in vitro model of hemoadsorption suggests the possible application in vivo of this technique to reduce/normalize the concentrations of PFAS in patients exposed to water or environmental pollution.

Extracorporeal Techniques in Kidney Failure.

During the last decades, various strategies have been optimized to enhance clearance of a variable spectrum of retained molecules to ensure hemodynamic tolerance to fluid removal and improve long-term survival in patients affected by kidney failure. Treatment effects are the result of the interaction of individual patient characteristics with device characteristics and treatment prescription. Historically, the nephrology community aimed to provide adequate treatment, along with the best possible quality of life and outcomes. In this article, we analyzed blood purification techniques that have been developed with their different characteristics.

Neutrophil Gelatinase-Associated Lipocalin in Peritoneal Dialysis-Related Peritonitis: Correlation with White Blood Cells over Time and a Possible Role as the Outcome Predictor.

INTRODUCTION: The present study aimed to monitor peritoneal neutrophil gelatinase-associated lipocalin (pNGAL) during peritonitis episodes and to enhance its diagnostic value by evaluating pNGAL at scheduled times in parallel with white blood cell (WBC) count. In addition, we investigated possible correlations between pNGAL and the etiology of peritonitis, evaluating it as a possible marker of the clinical outcome. METHODS: Twenty-two patients with peritoneal dialysis (PD)-related peritonitis were enrolled. Peritonitis was divided into Gram-positive, Gram-negative, polymicrobial, and sterile. WBC count and neutrophil gelatinase-associated lipocalin (NGAL) in PD effluent were measured at different times (days 0, 1, 5, 10, 15, and/or 20 and 10 days after antibiotic therapy discontinuation). NGAL was measured by standard quantitative laboratory-based immunoassay and by colorimetric NGAL dipstick (NGALds) (dipstick test). RESULTS: We found strong correlations between peritoneal WBC, laboratory-based NGAL, and NGALds values, both overall and separated at each time point. On day 1, we observed no significant difference in WBC, both NGALds (p = 0.3, 0.9, and 0.2) between Gram-positive, Gram-negative, polymicrobial, and sterile peritonitis. No significant difference has been found between de novo versus relapsing peritonitis for all markers (p > 0.05). We observed a parallel decrease of WBC and both NGAL in patients with favorable outcomes. WBC count and both pNGAL resulted higher in patients with negative outcomes (defined as relapsing peritonitis, peritonitis-associated catheter removal, peritonitis-associated hemodialysis transfer, peritonitis-associated death) at day 10 (p = 0.04, p = 0.03, and p = 0.05, respectively) and day 15 (p = 0.01, p = 0.04, and tendency for p = 0.005). There was a tendency toward higher levels of WBC and NGAL in patients with a negative outcome at day 5. No significant difference in all parameters was proven at day 1 (p = 0.3, p = 0.9, p = 0.2) between groups. CONCLUSION: This study confirms pNGAL as a valid and reliable biomarker for the diagnosis of PD-peritonitis and its monitoring. Its trend is parallel to WBC count during peritonitis episodes, in particular, patients with unfavorable outcomes.

Peritoneal Inflammation in PD-Related Peritonitis Induces Systemic Eryptosis: In Vitro and In Vivo Assessments.

Erythrocytes (RBCs) have a highly specialized and organized membrane structure and undergo programmed cell death, known as eryptosis. Our preliminary data show a significant increase in the eryptosis during peritoneal dialysis (PD)-associated peritonitis. The objectives of the present study were assessment of the incrementation of eryptosis in PD patients with peritonitis, evaluation of the relationship between systemic eryptosis in peritonitis and specific peritonitis biomarkers in PD effluent (PDE), and confirmation of the induction of eryptosis by peritonitis in a vitro setting. We enrolled 22 PD patients with peritonitis and 17 healthy subjects (control group, CTR). For the in vivo study, eryptosis was measured in freshly isolated RBCs. For the in vitro study, healthy RBCs were exposed to the plasma of 22 PD patients with peritonitis and the plasma of the CTR group for 2, 4, and 24 h. Eryptosis was evaluated by flow cytometric analyses in vivo and in vitro. PDE samples were collected for biomarkers analysis.The percentage of eryptotic RBCs was significantly higher in PD patients with peritonitis than in CTR (PD patients with peritonitis: 7.7; IQR 4.3-14.2, versus CTR: 0.8; IQR 0.7-1.3; p < 0.001). We confirmed these in vivo results by in vitro experiments: healthy RBCs incubated with plasma from PD patients with peritonitis demonstrated a significant increase in eryptosis compared to healthy RBCs exposed to plasma from the control group at all times. Furthermore, significant positive correlations were observed between eryptosis level and all analyzed peritoneal biomarkers of peritonitis. We investigated a potential connection between systemic eryptosis and peritoneal biomarkers of peritonitis. Up-regulation of inflammatory markers could explain the increased rate of systemic eryptosis during PD-related peritonitis.

Contemporary laboratory assessment of acute cardiorenal syndrome for early diagnosis: A call for action.

Acute cardiorenal syndrome (CRS), categorized as CRS type 1 and 3, is defined by the interplay of acute kidney injury or dysfunction and acute cardiac disease. For optimized diagnosis and management of CRS, strategies targeting multi-organ dysfunction must be adopted. Early diagnosis of acute CRS is important to enable timely initiation of appropriate treatment to prevent serious morbidity and mortality; however, traditional biomarkers are suboptimal. Over the past 2 decades, numerous biomarkers have been investigated for a better and more rapid diagnosis of CRS. Yet, the uptake of these contemporary biomarkers has been slow, possibly owing to the use of imperfect gold-standard reference tests. We believe that there is now scope for use of contemporary laboratory test panels to improve the diagnosis of acute CRS. In this review, we briefly discuss a proposed set of biomarkers for the diagnosis of type 1 and type 3 CRS.

Prognostic models to predict complete resolution of hypertension after adrenalectomy in primary aldosteronism: A systematic review and meta-analysis.

Complete resolution of hypertension (CRH) after adrenalectomy for primary aldosteronism is far from a certainty. Although several prognostic models have been proposed to predict outcome after adrenalectomy, studies have not clarified which of the available models can be used reliably in clinical practice. To identify, describe and appraise all prognostic models developed to predict CRH, and meta-analyse their predictive performances. We searched MEDLINE, Embase and Web of Science for development and validation studies of prognostic models. After selection, we extracted descriptive statistics and aggregated area under the receiver operator curve (AUC) using meta-analysis. From 25 eligible studies, we identified 12 prognostic models used for predicting CRH after total adrenalectomy in primary aldosteronism. We report the results for 3 models that had available data from at least 3 external validation studies: the primary aldosteronism surgical outcome (PASO) score (AUC: 0.81; 95% confidence interval [CI]: 0.74-0.86; 95% predictive interval [PI]: 0.04-1.00), Utsumi nomogram (AUC: 0.79; 95% CI: 0.72-0.85; 95% PI: 0.03-1.00) and the aldosteronoma resolution score (ARS) model (AUC: 0.77; 95% CI: 0.74-0.80; 95% PI: 0.59-0.86 for all studies and AUC: 0.80; 95% CI: 0.75-0.85; 95% PI: 0.57-0.93 for the studies with the same adrenal vein sampling-guided adrenalectomy rate compared to the models meta-analysed). The PASO score, Utsumi nomogram and ARS model showed comparable discrimination performance to predict CRH in primary aldosteronism. Unlike the ARS model, the number of external validation studies for the PASO score and the Utsumi nomogram was relatively low to draw definite conclusions.

Impact of medium cut-off membranes on S100A12 and soluble receptor for advanced glycation end products.

INTRODUCTION: Of the most remarkable molecules associated with atherosclerosis and the cardiovascular outcome are S100A12 (10,379.5 Da) and soluble receptor for advanced glycation end products (sRAGE-42,803 Da) in the hemodialysis (HD) population. We designed a study investigating the effects of the medium cut-off (MCO) dialyzers focusing on S100A12 and sRAGE in HD patients compared with low-flux and high-flux dialyzers. METHODS: This single-site, prospective, observational study comprises age and sex-matched HD groups (low-flux, high-flux, and MCO). Blood samples were drawn at baseline (predialysis and postdialysis) and the sixth month (predialysis). RESULTS: Groups had similar demographic features and laboratory parameters. Baseline S100A12 levels of the groups were similar [34.3 (±66.5), 30.9 (±42.7), and 40.6 (±29.6); p = 0.13]. Compared to their baseline, the sixth-month S100A12 levels were constant in low-flux and high-flux group and significantly lower in MCO group (p = 0.16, p = 0.33, and p = 0.004). Baseline sRAGE levels of the groups were similar at baseline [2.8 (±0.8), 2.7 (±0.6), and 2.6 (±0.7); p = 0.65], and the sixth-month [2.9 (±0.5), 2.4 (±0.7), and 2.4 (±0.8); p = 0.24]. sRAGE levels remained constant in all groups [p = 0.84, p = 0.13, and p = 0.39]. S100A12/sRAGE ratio at baseline and sixth month was constant in low-flux [22.3 (±63.7) and 18.1 (±24.8); p = 0.17] and high-flux groups [11.9 (±15.3) and 13.1 (±5.8); p = 0.26], the ratio decreased significantly in MCO group [16.5 (±11.6) to 7.8 (±5.5); p = 0.03]. CONCLUSION: Our study suggests that prolonged use of MCO dialyzers is associated with better S100A12 and sRAGE levels. Long-term studies with larger samples are needed to understand the effects of a better S100A12-sRAGE profile provided by MCO dialyzers on HD patients' cardiovascular outcomes.

Peritoneal dialysis and acute kidney injury in acute brain injury patients.

Acute kidney injury (AKI) is a heterogeneous syndrome with multiple etiologies. It occurs frequently in the neurocritical intensive care unit and is associated with greater morbidity and mortality. In this scenario, AKI alters the kidney-brain axis, exposing patients who receive habitual dialytic management to greater injury. Various therapies have been designed to mitigate this risk. Priority has been placed by KDIGO guidelines on the use of continuous over intermittent acute kidney replacement therapies (AKRT). On this background, continuous therapies have a pathophysiological rationale in patients with acute brain injury. A low-efficiency therapy such as PD and CRRT could achieve optimal clearance control and potentially reduce the risk of secondary brain injury. Therefore, this work will review the evidence on peritoneal dialysis as a continuous AKRT in neurocritical patients, describing its benefits and risks so it may be considered as an option when deciding among available therapeutic options.

The role of endotoxin in septic shock.

Septic shock can be caused by a variety of mechanisms including direct effects of bacterial toxins such as endotoxin. Annually, approximately 5-7 million patients worldwide develop sepsis with very high endotoxin activity in the blood and more than half die. The term endotoxic septic shock has been used for these patients but it is important to emphasize that endotoxin may be a factor in all forms of septic shock including non-bacterial etiologies like COVID-19 since translocation of bacterial products is a common feature of septic shock. A pattern of organ failure including hepatic dysfunction, acute kidney injury and various forms of endothelial dysfunction ranging from disseminated intravascular coagulation to thrombotic microangiopathy characterize endotoxic septic shock. However, while characteristic, the clinical phenotype is not unique to patients with high endotoxin, and the diagnosis relies on the measurement of endotoxin activity in addition to clinical assessment. Therapies for endotoxic septic shock are limited with immune modulating therapies under investigation and extracorporeal blood purification still controversial in many parts of the world.