The role of blood purification therapies in the treatment of chronic kidney disease-associated pruritus: a systematic review.

Chronic kidney disease-associated pruritus (CKD-aP) is a common complication in dialysis patients which is not fully addressed by pharmacological and dialytic therapy. The objective was to review the literature on the effects of extracorporeal blood purification modalities on CKD-aP. The population comprised patients aged ≥18 years on chronic dialysis. PubMed, Embase, and Medline were systematically searched until February 2024 for clinical studies comparing the effect of different dialysis modalities on pruritus intensity. Two reviewers extracted data independently. Risk of bias for randomized controlled trials (RCTs) was assessed using the Cochrane tool. Any extracorporeal blood purification therapy for the treatment of CKD-aP was included. Outcome was quantitative change in pruritus intensity on a validated itching scale. This review included eight RCTs examining five different dialysis modalities, three observational studies examining three dialysis modalities, and six prospective clinical trials assessing four dialysis modalities. These treatments included peritoneal dialysis, low-flux and high-flux dialysis, hemodiafiltration, expanded hemodialysis, hemadsorption, hemodiafiltration with endogenous reinfusion and dialysis with polymethylmethacrylate membrane. Risk of bias was high in most studies. The largest body of evidence was found for the efficacy of hemadsorption. Limitations of evidence included heterogeneity in diagnostic tools and treatment, risk of selection bias, small sample sizes and short follow-up durations that made it challenging to perform a robust systematic review and meta-analysis. Despite the high prevalence of pruritus among dialysis patients, current evidence for efficacy of standard dialytic treatment is weak. The only technique that appears to be effective is hemoadsorption alone or coupled with hemodialysis. More high-quality studies are needed to confirm the long-term benefits.

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.

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.

Efficacy of modern therapies for heart failure with reduced ejection fraction in specific population subgroups: a systematic review and network meta-analysis.

INTRODUCTION: The efficacy and safety of emerging therapies for heart failure with reduced ejection fraction (HFrEF) have never been compared in specific subgroups of patients. METHODS: Pubmed, Cochrane Registry, Web of Science, Scopus and EMBASE libraries were used to extract data. We used the following keywords: (heart failure with reduced ejection fraction OR HFrEF) AND (treatment OR therapy) OR (cardiovascular death) OR (hospitalization for heart failure). We compared randomized clinical trials (RCTs) for HFrEF emerging therapies focusing on elderly (patients > 65 years old and > 75 years old), chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) < 60 ml/min), diabetic patients, ischemic patients, New York Heart Association (NYHA) class III/IV, female sex, patients on sacubitril/valsartan (S/V). The primary outcome was the efficacy composite endpoint of cardiovascular death (CVD) and HF hospitalization (HFH). RESULTS: S/V significantly reduced the primary outcome in patients > 65 years old (RR: 0.80; 95%CI: 0.68-0.94) and with CKD (RR: 0.79; 95%CI: 0.69-0.90); dapagliflozin in patients >65 (RR: 0.72; 95%CI: 0.60-0.86) and >75 years old (RR: 0.68; 95%CI: 0.53-0.87), in those with CKD (RR: 0.72; 95%CI: 0.59-0.88), diabetic (RR: 0.75; 95%CI: 0.63-0.89) and ischemic patients (RR: 0.77; 95%CI: 0.65-0.92); empagliflozin in patients >65 years old (RR: 0.78; 95%CI: 0.66-0.93), diabetic (RR: 0.72; 95%CI: 0.60-0.86), ischemic (RR: 0.82; 95%CI: 0.68-0.99), female sex (RR: 0.59; 95%CI: 0.44-0.79) and in patients on S/V (RR: 0.64; 95%CI: 0.45-0.91); vericiguat in patients with CKD (RR: 0.84; 95%CI: 0.73-0.97) and NYHA class III/IV (RR: 0.87; 95%CI: 0.77-0.98); OM in ischemic (RR: 0.90; 95%CI:0.82-0.99) and NYHA III/IV (RR: 0.88; 95%CI: 0.80-0.97) patients. CONCLUSION: Emerging HFrEF therapies show a clinical benefit with the reduction of the primary composite endpoint of CVD and HFH, with each drug being more effective in specific patient population.

Recommendations for clinical trial design in acute kidney injury from the 31st acute disease quality initiative consensus conference. A consensus statement.

PURPOSE: Novel interventions for the prevention or treatment of acute kidney injury (AKI) are currently lacking. To facilitate the evaluation and adoption of new treatments, the use of the most appropriate design and endpoints for clinical trials in AKI is critical and yet there is little consensus regarding these issues. We aimed to develop recommendations on endpoints and trial design for studies of AKI prevention and treatment interventions based on existing data and expert consensus. METHODS: At the 31st Acute Disease Quality Initiative (ADQI) meeting, international experts in critical care, nephrology, involving adults and pediatrics, biostatistics and people with lived experience (PWLE) were assembled. We focused on four main areas: (1) patient enrichment strategies, (2) prevention and attenuation studies, (3) treatment studies, and (4) innovative trial designs of studies other than traditional (parallel arm or cluster) randomized controlled trials. Using a modified Delphi process, recommendations and consensus statements were developed based on existing data, with > 90% agreement among panel members required for final adoption. RESULTS: The panel developed 12 consensus statements for clinical trial endpoints, application of enrichment strategies where appropriate, and inclusion of PWLE to inform trial designs. Innovative trial designs were also considered. CONCLUSION: The current lack of specific therapy for prevention or treatment of AKI demands refinement of future clinical trial design. Here we report the consensus findings of the 31st ADQI group meeting which has attempted to address these issues including the use of predictive and prognostic enrichment strategies to enable appropriate patient selection.

Antibiotics Removal during Continuous Renal Replacement Therapy in Septic Shock Patients: Mixed Modality Versus "Expanded Haemodialysis".

BACKGROUND AND OBJECTIVE: Renal replacement therapy (RRT) plays a critical role in antimicrobial removal, particularly for low-molecular-weight drugs with low plasma protein binding, low distribution volume and hydrophilicity. Medium cut-off (MCO) membranes represent a new generation in dialysis technology, enhancing diffusive modality efficacy and increasing the cut-off from 30 to 45 kDa, crucial for middle molecule removal. This monocentric randomized crossover pilot study aimed to evaluate the impact of continuous haemodialysis with MCO membrane (MCO-CVVHD) on the removal of piperacillin, tazobactam and meropenem compared with continuous veno-venous hemodiafiltration with standard high-flux membrane (HFM-CVVHDF). METHODS: Twenty patients were randomized to undergo MCO-CVVHD followed by HFM-CVVHDF or vice versa. Extraction ratio (ER), effluent clearance (Cleff) and treatment efficiency were assessed at various intervals. Antibiotic nadir plasma levels were measured for both treatment days. RESULTS: HFM-CVVHDF showed greater ER compared with MCO-CVVHD for meropenem (ß = - 8.90 (95% CI - 12.9 to - 4.87), p < 0.001) and tazobactam (ß = - 8.29 (95% CI - 13.5 to - 3.08), p = 0.002) and Cleff for each antibiotic (meropenem ß = - 10,206 (95% CI - 14,787 to - 5787), p = 0.001); tazobactam (ß = - 4551 (95% CI - 7781 to - 1322), p = 0.012); piperacillin (ß = - 3913 (95% CI - 6388 to - 1437), p = 0.002), even if the carryover effect influenced the Cleff for meropenem and tazobactam. No difference was observed in nadir plasma concentrations or efficiency for any antibiotic. Piperacillin (ß = - 38.1 (95% CI - 47.9 to - 28.3), p < 0.001) and tazobactam (ß = - 4.45 (95% CI - 6.17 to - 2.72), p < 0.001) showed lower nadir plasma concentrations the second day compared with the first day, regardless the filter type. CONCLUSION: MCO demonstrated comparable in vivo removal of piperacillin, tazobactam and meropenem to HFM.

Cardiorenal Syndrome and Inflammation: A Forgotten Frontier Resolved by Sorbents?

Cardiorenal syndrome (CRS) describes the maladaptive relationship between heart and kidney dysfunction, with different pathways perpetuating the pathophysiology. Inflammation is one of these mechanisms. It contributes to the final nonhemodynamic pathways of organ dysfunction in the heart-kidney cross-talk. It may be a mediator and amplifier of this pathological communication, playing a vital role in both acute and chronic cardiorenal dysfunction. Current therapeutic strategies are not satisfactory in mitigating the inflammatory pathway in CRS. Hemoadsorption overcomes this limitation, and the soluble mediators of inflammation are potentially amenable to removal by hemoadsorption. This perspective article describes the inflammatory mechanisms in CRS and the rationality of using hemoadsorption in this scenario.

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.

Use of eHealth and remote patient monitoring: a tool to support home dialysis patients, with an emphasis on peritoneal dialysis.

Implementing eHealth requires technological advancement, universal broadband and internet access, and devices to conduct telemedicine and remote patient monitoring in end-stage kidney disease patients receiving home dialysis. Although eHealth was beginning to make inroads in this patient population, the COVID-19 pandemic spurred telemedicine usage when many regulations were waived during the Public Health Emergency to limit the spread of infection by endorsing social distancing. At the same time, two-way communication automatic peritoneal dialysis cyclers were introduced to advance remote patient monitoring. Despite the numerous advantages and potential benefits afforded by both procedures, challenges and untapped resources remain to be addressed. Continuing research to assess the use of eHealth and technological innovation can make eHealth a powerful tool in home dialysis. We review the past, present and future of eHealth and remote patient monitoring in supporting home dialysis.

Exploring the Role of Cell-Free Nucleic Acids and Peritoneal Dialysis: A Narrative Review.

INTRODUCTION: Cell-free nucleic acids (cf-NAs) represent a promising biomarker of various pathological and physiological conditions. Since its discovery in 1948, cf-NAs gained prognostic value in oncology, immunology, and other relevant fields. In peritoneal dialysis (PD), blood purification is performed by exposing the peritoneal membrane. Relevant sections: Complications of PD such as acute peritonitis and peritoneal membrane aging are often critical in PD patient management. In this review, we focused on bacterial DNA, cell-free DNA, mitochondrial DNA (mtDNA), microRNA (miRNA), and their potential uses as biomarkers for monitoring PD and its complications. For instance, the isolation of bacterial DNA in early acute peritonitis allows bacterial identification and subsequent therapy implementation. Cell-free DNA in peritoneal dialysis effluent (PDE) represents a marker of stress of the peritoneal membrane in both acute and chronic PD complications. Moreover, miRNA are promising hallmarks of peritoneal membrane remodeling and aging, even before its manifestation. In this scenario, with multiple cytokines involved, mtDNA could be considered equally meaningful to determine tissue inflammation. CONCLUSIONS: This review explores the relevance of cf-NAs in PD, demonstrating its promising role for both diagnosis and treatment. Further studies are necessary to implement the use of cf-NAs in PD clinical practice.

CCL14 testing to guide clinical practice in patients with AKI: Results from an international expert panel.

PURPOSE: Urinary C-C motif chemokine ligand 14 (CCL14) is a strong predictor of persistent stage 3 acute kidney injury (AKI). Multiple clinical actions are recommended for AKI but how these are applied in individual patients and how the CCL14 test results may impact their application is unknown. METHODS: We assembled an international panel of 12 experts and conducted a modified Delphi process to evaluate patients at risk for persistent stage 3 AKI (lasting 72 hours or longer). Using a Likert scale, we rated 11 clinical actions based on international guidelines applied to each case before and after CCL14 testing and analyzed the association between the strength and direction of recommendations and CCL14 results. RESULTS: The strength and direction of clinical recommendations were strongly influenced by CCL14 results (P < 0.001 for the interaction). Nine (82%) recommendations for clinical actions were significantly impacted by CCL14 results (P < 0.001 comparing low to highest CCL14 risk category). CONCLUSIONS: Most recommendations for care of patients with stage 2-3 by an international panel of experts were strongly modified by CCL14 test results. This work should set the stage for clinical practice protocols and studies to determine the effects of recommended actions informed by CCL14.

Tissue Inhibitor Metalloproteinase-2·IGF-Binding Protein 7 for the Prediction of Acute Kidney Injury following Cardiac Surgery.

INTRODUCTION: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common complication associated with increased morbidity and mortality. Tissue inhibitor metalloproteinase-2·insulin-like growth factor-binding protein 7 (TIMP-2·IGFBP7) determines tubular stress markers, which may occur prior to tubular damage. Previous studies on the use of TIMP-2·IGFBP7 for the prediction of CSA-AKI showed divergent results. Therefore, this study aimed to explore the predictive value of TIMP-2·IGFBP7 measurements for the early detection of acute kidney injury (AKI) and short-term adverse outcomes after cardiac surgery. METHODS: In the prospective cohort study, blood and urine samples were collected 6-12 h after cardiac surgery. Blood samples to monitor serum creatinine levels were additionally extracted from days 1 to 7. AKI was defined based on the KDIGO consensus guidelines. AKI within 7 days following surgery was the primary outcome. The initiation of renal replacement therapy, in intensive care unit mortality, and the combination of both were secondary outcomes. RESULTS: A total of 557 patients were enrolled; 134 (24.06%) of them developed AKI and 33 (5.9%) had moderate or severe AKI. AKI developed more frequently in elderly patients with diabetes or with higher baseline serum creatinine levels. Patients with AKI had higher EuroSCORE II, Cleveland Clinic Score, and simplified renal index (SRI) than those without AKI. Urinary TIMP-2·IGFBP7 was significantly higher in patients with AKI. The area under the curve was 0.66 in predicting all AKI and 0.70 in predicting stages 2 and 3 AKI. The resulting sensitivity and specificity were 44.0% and 83.9%, respectively, for a calculated threshold TIMP-2·IGFBP7 value of 0.265 (ng/mL)2/1,000. The TIMP-2·IGFBP7 values, SRI score, and age were significantly associated with AKI within 7 days postoperatively. A total of 33 patients reached the composite endpoint; the percentage of patients who reached the composite endpoint in the TIMP-2·IGFBP7 of >0.265 (ng/ml)2/1,000 group was significantly higher than that of ≤0.265 (ng/mL)2/1,000 group. CONCLUSIONS: Postoperative implementation of TIMP-2·IGFBP7 improved the prediction of CSA-AKI and may aid in identifying patients at risk of short-term adverse outcomes. We identified an ideal calculated cutoff value of 0.265 (ng/mL)2/1,000 for the prediction of CSA-AKI among all AKI patients.

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.

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.

Immunomodulation Driven by Theranova Filter during a Single HD Session.

Background: Patients with end-stage kidney disease (ESKD) have altered immunity. Patients on hemodialysis (HD) present a coexistence of immunodeficiency and activation of the immune system. We evaluated the immunophenotypic profile induced by the medium cut-off of Theranova filter during a single HD session in the same individual. Methods: This pilot observational study explored 11 patients (75 ± 8 years and 73% male). Blood samples were collected prior to (predialytic, PRE) and after 4 h (postdialytic, POST) standard HD session with a medium cut-off, polyarylethersulfone and polyvinylpyrrolidone blend, BPA-free membrane. We performed an immunophenotyping characterization by using flow cytometry. We evaluated eryptosis RBCs and HLA-DR expression on monocytes and Treg cells. Results: The percentages of eryptosis in lymphocytes (CD3+), lymphocyte T helper (CD3+ and CD4+) cells, and monocytes (CD45+ and CD14+) were similar pre- and post-HD. On the contrary, HLA-DR expression and Treg cell numbers significantly decreased after HD. Conclusions: Many studies have focused on the comparison between healthy volunteers and HD patients, but very few have focused on the changes that occur after an HD session in the same individual. With this pilot observational study, we have revealed an immunomodulation driven by HD treatment with Theranova filter. Our preliminary results can be considered to be a hypothesis, generating and stimulating further studies with better designs and larger populations.

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.

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.

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.