Search Results (17)

Comparisons of hemodiafiltration with hemodialysis have indicated significantly improved survival when the substitution fluid volume is greater than 23 L per treatment. This survival benefit has been ascribed to better removal of high-molecular-weight uremic toxins. However, with hemodiafiltration, predialysis levels of some high-molecular-weight toxins are only modestly reduced and remain far above levels measured in subjects with normal kidney function. In the present review, the potential role of other factors associated with hemodiafiltration that may beneficially impact survival relative to that seen with hemodialysis is explored. Factors analyzed include removal of relatively small uremic toxins such as urea, phosphate, and oxalate, a reduced incidence of intradialytic hypotension in some studies, possibly related to lower extracorporeal circuit temperature, benefits associated with use of ultrapure dialysis solution, and potential benefits associated with avoidance of thrice-weekly saline infusion for priming, volume replacement, and rinse back. The survival benefit associated with each of these factors may be small, but collectively, they may have a clinical impact. Full article

Background: Critically ill children with cancer are vulnerable to sepsis and septic shock, secondary hemophagocytic lymphohistiocytosis (HLH), cytokine release syndrome, delayed chemotherapy clearance, and multiorgan dysfunction. Although hemoadsorption can remove inflammatory mediators and selected toxins, evidence in pediatric oncology remains limited and heterogeneous. Objective: To systematically review the indications, technical application, biomarker and physiologic findings, safety reporting, and clinical outcomes of hemoadsorption in critically ill pediatric oncology and hemato-oncology patients. Methods: We conducted a PRISMA-guided systematic review of PubMed, Scopus, and Web of Science from January 2017 to 1 June 2026, supplemented by reference screening. The search strategy was expanded to capture cartridge-based hemoadsorption and related extracorporeal blood purification modalities, including albumin dialysis systems, but direct synthesis was restricted to cartridge-based hemoadsorption. Evidence was stratified as direct pediatric oncology evidence, supportive hemato-oncology/transplant evidence, or contextual mixed pediatric critical-care evidence. Because included reports were small, uncontrolled, and clinically heterogeneous, synthesis followed a structured narrative approach without meta-analysis. Results: Twelve reports met the inclusion criteria; most were case reports, case series or retrospective observational studies. Hemoadsorption was most often described for septic shock, sepsis-like hyperinflammation, or secondary HLH, with smaller experience in delayed methotrexate clearance, CAR-T-cell-associated cytokine release syndrome, and post-transplant hyperbilirubinemia. Reported devices included CytoSorb, Jafron HA330, and HA230. Direct pediatric oncology reports described before–after reductions in IL-6, IL-10, C-reactive protein, procalcitonin, or ferritin, together with changes in oxygenation, vasoactive support, or organ dysfunction scores. However, all findings were vulnerable to confounding by concurrent antimicrobials, immunomodulation, kidney replacement therapy, source control, and natural recovery. Mortality outcomes were reported using non-equivalent horizons and were summarized narratively. Conclusions: Hemoadsorption has been attempted as adjunctive rescue support in selected critically ill pediatric oncology and hemato-oncology patients. Current evidence is insufficient to determine treatment effect, survival benefit, optimal timing, device selection, anticoagulation strategy, or pharmacokinetic safety. Full article

Background and Clinical Significance: Extracorporeal therapies such as hemodialysis, continuous renal replacement therapy (CRRT) or therapeutic plasma exchange (TPE) are mainstay treatments for acute toxins, venoms and poisonings. Ibuprofen is a common drug implicated in acute toxicity, with a major complication being acute kidney injury (AKI). As such, these patients often receive hemodialysis or CRRT, which do not remove substances with high protein binding (>80%) and low volumes of distribution (Vd) (<0.2 L/kg). The pharmacokinetics of ibuprofen have these characteristics. While hemodialysis or CRRT can clear the accumulated toxic metabolites, they do not remove the ibuprofen that causes renal injury. In contrast, TPE can remove protein-bound drugs such as ibuprofen. Case Presentation: We describe the case of a previously healthy young male who presented with AKI due to ibuprofen toxicity requiring concurrent continuous renal replacement therapy and plasma exchange. Conclusions: TPE in conjunction with hemodialysis or CRRT is an effective treatment modality for ibuprofen toxicity. Full article

Eryptosis is a programmed cellular death that leads to the removal of defective red blood cells (RBCs). It is driven by convergent intracellular pathways centered on cytosolic Ca²⁺ overload, ceramide formation, caspase and calpain activation, disruption of membrane phospholipid asymmetry, and the externalization of phosphatidylserine on the cell surface, which marks the cell for clearance by macrophages. In hemodialysis (HD), intermittent extracorporeal circulation exposes erythrocytes to mechanical stress, bio-incompatible membrane surfaces, and rapid osmotic and ionic shifts. Experimental evidence indicates that osmotic shock induces eryptosis through synergistic Ca²⁺ influx and sphingomyelinase-dependent ceramide generation, providing a mechanistic framework for intradialytic erythrocyte injury. Clinical studies report heterogeneous eryptotic responses during HD, reflecting the balance between toxin removal and procedure-related stress. In contrast, peritoneal dialysis (PD) imposes sustained exposure to hyperosmolar, glucose-based solutions and is strongly influenced by inflammation and residual kidney function. Clinical and experimental data consistently demonstrate increased eryptosis in PD patients, with marked amplification during peritonitis and close associations with inflammatory mediators. This review integrates mechanistic and clinical evidence on eryptosis in HD and PD, highlights modality-specific triggers converging on shared downstream pathways and discusses translational implications and research priorities for improving dialysis biocompatibility and anemia management. Full article

Extracorporeal dialysis for uremic toxin removal and fluid regulation relies on specialized dialyzers whose membranes differ markedly in polymer chemistry, pore architecture, adsorption capacity, surface bioactivity, and convective performance. These structural and material distinctions result in wide variation in the clearance of chemically diverse uremic solutes. Despite the expanding range of dialyzer options, membrane selection in clinical practice remains largely non-individualized. In this review, we propose a phenotype-based model for dialyzer membrane selection. We outline how distinct membrane families achieve differential solute clearance and integrate these functional characteristics into a framework that considers residual kidney function, nutritional and inflammatory status, cardiovascular physiology, protein-bound toxin burden, and hemodynamic vulnerability. Because access to advanced membranes varies across regions and dialysis providers, implementation will require adaptation to local formulary constraints. Nevertheless, aligning membrane properties with patient-specific toxin profiles offers a promising strategy to optimize extracorporeal therapy and improve outcomes in chronic dialysis. Full article

Background: Valproic acid (VPA) poisoning has a dynamic clinical course and may require extracorporeal toxin removal (ECTR) in severe cases. Intermittent hemodialysis is the preferred ECTR technique; however, clinical experience with expanded hemodialysis (HDx) using medium cut-off (MCO) membranes in acute VPA intoxication is scarce. We describe a case of severe VPA poisoning managed with intermittent HDx and outline the clinical rationale and kinetic response. Case Report: A 54-year-old woman presented to the emergency department after accidental presumably ingesting approximately 4 g of VPA, with depressed consciousness (Glasgow Coma Scale 7) and metabolic acidosis (pH 7.10, HCO₃⁻ 13 mmol/L, PCO₂ 50 mmHg, lactate 2.8 mmol/L, ionized calcium 0.8 mmol/L, elevated anion gap). Initial plasma VPA was 262.99 µg/mL, ammonia was 14 µmol/L, and cranial computed tomography showed no acute abnormalities. ECTR was initiated in the intensive care unit as intermittent HDx using an MCO dialyzer for 4 h. Serial VPA concentrations were obtained before treatment, at 2 h, and at the end of the session to guide real-time prescription adjustment, with an increase in blood flow from 200 to 230 mL/min. Results: VPA decreased from 262.99 µg/mL pre-HD to 141.48 µg/mL at 2 h (46.2% reduction) and 97.81 µg/mL at 4 h (62.8% reduction), with clear improvement in the level of consciousness. A mild post-dialysis rebound was observed (100.07 µg/mL at 14 h). The patient recovered without additional ECTR and was discharged with normalized VPA levels on follow-up. Conclusions: In this patient, intermittent HDx with an MCO membrane was feasible, well tolerated, and associated with rapid VPA clearance and neurological recovery. Serial drug monitoring enabled bedside optimization of the dialysis prescription and post-treatment evaluation. A single HDx session was sufficient, and VPA therapy was safely reintroduced under close monitoring. Full article

Background: Pediatric sepsis presents a severe risk to immunocompromised children, especially those with cancer or pre-existing conditions, posing a significant threat to their lives. Cytokine hemadsorption has emerged as a promising therapeutic approach for managing sepsis and severe inflammatory conditions in critically ill patients. This innovative method involves eliminating pro-inflammatory cytokines from the bloodstream, targeting the underlying hyper-inflammatory response often seen in critical illnesses. Study aim: The study aim is to examine and compare the efficacy of HA330 and CytoSorb for extracorporeal blood purification in septic children with oncology. Methods: In this retrospective observational study, we examine 20 cases to assess the effectiveness of hemoperfusion therapy using hemoadsorption devices in pediatric septic patients with oncology. Our focus is on the use of HA330 and Cytosorb hemoadsorption devices, both designed to remove bacterial toxins and inflammatory agents from the bloodstream. Results: Our study reveals that hemoadsorption with HA330 and CytoSorb effectively treats septic children with oncological conditions. Conclusions: The presented findings suggest no statistically significant difference between the two devices in reducing the levels of the assessed parameters for extracorporeal blood purification in this patient population. Full article

During the progression of chronic kidney disease (CKD), the retention of uremic toxins plays a key role in the development of uremic syndrome. Knowledge about the nature and biological impact of uremic toxins has grown exponentially over the past decades. However, the science on reducing the concentration and effects of uremic toxins has not advanced in parallel. Additionally, the focus has remained for too long on dialysis strategies, which only benefit the small fraction of people with CKD who suffer from advanced kidney disease, whereas uremic toxicity effects are only partially prevented. This article reviews recent research on alternative methods to counteract uremic toxicity, emphasizing options that are also beneficial in the earlier stages of CKD, with a focus on both established methods and approaches which are still under investigation or at the experimental stage. We will consequently discuss the preservation of kidney function, the prevention of cardiovascular damage, gastro-intestinal interventions, including diet and biotics, and pharmacologic interventions. In the final part, we also review alternative options for extracorporeal uremic toxin removal. The future will reveal which of these options are valid for further development and evidence-based assessment, hopefully leading to a more sustainable treatment model for CKD than the current one. Full article

Dialysis is life-saving for an exponentially growing number of kidney failure patients. Yet, the current concept also has several drawbacks, such as high societal cost, incomplete kidney function replacement, dismal outcomes, low quality of life and a considerable ecologic footprint. In spite of many changes over the last fifty years, the original concept remained largely unmodified and the drawbacks did not disappear. In this article, we present a number of alternative solutions that are currently considered or tested which might have a potential impact on uremic toxin concentration, quality of life or environmental footprint that goes beyond what is currently achieved with traditional dialysis. These comprise applications of regenerative medicine; bioartificial kidney; conceptual changes in extracorporeal removal; energy-neutral, water-limiting dialysis; material recycling; keto-analogues; xenobiotics; and preservation of residual kidney function. As metabolism generating uremic toxins also generates beneficial compounds, some of these options may also maintain or restore this balance in contrast to dialysis that likely removes without distinction. All proposed options are also exemplary of how out-of-the-box thinking is needed to disrupt the status quo in treatment of kidney diseases that has now persisted for too long. Full article

Bacterial endotoxin, also known as lipopolysaccharide (LPS), plays a major role in the initiation of sepsis, a severe inflammatory condition. Removal of the toxin from blood is one accepted method of patient treatment. Polymyxin B (PMB)-modified columns have been employed successfully for this purpose via extra-corporeal blood-flow systems that incorporate a cartridge for toxin removal. Herein we demonstrate that PMB-modified glass beads are able to reduce the presence of LPS competitively with the equivalent fiber column used in a commercial cartridge. Analysis by gas chromatography-mass spectrometry and ELISA of released fatty acids from the toxin indicates that PMB does not physically capture or significantly remove LPS from the blood samples. In reality, interaction between the surface-bound PMB and the toxin may lead to disaggregation or monomerization of LPS aggregates. As aggregates are the bioactive form of LPS, it is possible that the monomerization of these entities may be the mechanism by which their toxicity is reduced. Moreover, this work indicates that LPS monomers are stabilized subsequent to disaggregation induced by PMB. Full article

Removal of protein-bound uremic toxins (PBUTs) during conventional dialysis is insufficient. PBUTs are associated with comorbidities and mortality in dialysis patients. Albumin is the primary carrier for PBUTs and only a small free fraction of PBUTs are dialyzable. In the past, we proposed a novel method where a binding competitor is infused upstream of a dialyzer into an extracorporeal circuit. The competitor competes with PBUTs for their binding sites on albumin and increases the free PBUT fraction. Essentially, binding competitor-augmented hemodialysis is a reactive membrane separation technique and is a paradigm shift from conventional dialysis therapies. The proposed method has been tested in silico, ex vivo, and in vivo, and has proven to be very effective in all scenarios. In an ex vivo study and a proof-of-concept clinical study with 18 patients, ibuprofen was used as a binding competitor; however, chronic ibuprofen infusion may affect residual kidney function. Binding competition with free fatty acids significantly improved PBUT removal in pre-clinical rat models. Based on in silico analysis, tryptophan can also be used as a binding competitor; importantly, fatty acids or tryptophan may have salutary effects in HD patients. More chemoinformatics research, pre-clinical, and clinical studies are required to identify ideal binding competitors before routine clinical use. Full article

Accumulation of uremic toxins represents one of the major contributors to the rapid progression of chronic kidney disease (CKD), especially in patients with end-stage renal disease that are undergoing dialysis treatment. In particular, protein-bound uremic toxins (PBUTs) seem to have an important key pathophysiologic role in CKD, inducing various cardiovascular complications. The removal of uremic toxins from the blood with dialytic techniques represents a proved approach to limit the CKD-related complications. However, conventional dialysis mainly focuses on the removal of water-soluble compounds of low and middle molecular weight, whereas PBTUs are strongly protein-bound, thus not efficiently eliminated. Therefore, over the years, dialysis techniques have been adapted by improving membranes structures or using combined strategies to maximize PBTUs removal and eventually prevent CKD-related complications. Recent findings showed that adsorption-based extracorporeal techniques, in addition to conventional dialysis treatment, may effectively adsorb a significant amount of PBTUs during the course of the sessions. This review is focused on the analysis of the current state of the art for blood purification strategies in order to highlight their potentialities and limits and identify the most feasible solution to improve toxins removal effectiveness, exploring possible future strategies and applications, such as the study of a synergic approach by reducing PBTUs production and increasing their blood clearance. Full article

Hydrophobic uremic toxins accumulate in patients with chronic kidney disease, contributing to a highly increased cardiovascular risk. The clearance of these uremic toxins using current hemodialysis techniques is limited due to their hydrophobicity and their high binding affinity to plasma proteins. Adsorber techniques may be an appropriate alternative to increase hydrophobic uremic toxin removal. We developed an extracorporeal, whole-blood bifunctional adsorber particle consisting of a porous, activated charcoal core with a hydrophilic polyvinylpyrrolidone surface coating. The adsorption capacity was quantified using analytical chromatography after perfusion of the particles with an albumin solution or blood, each containing mixtures of hydrophobic uremic toxins. A time-dependent increase in hydrophobic uremic toxin adsorption was depicted and all toxins showed a high binding affinity to the adsorber particles. Further, the particle showed a sufficient hemocompatibility without significant effects on complement component 5a, thrombin-antithrombin III complex, or thrombocyte concentration in blood in vitro, although leukocyte counts were slightly reduced. In conclusion, the bifunctional adsorber particle with cross-linked polyvinylpyrrolidone coating showed a high adsorption capacity without adverse effects on hemocompatibility in vitro. Thus, it may be an interesting candidate for further in vivo studies with the aim to increase the efficiency of conventional dialysis techniques. Full article

The protein-bound uremic toxins para-cresyl sulfate (pCS) and indoxyl sulfate (IS) are associated with cardiovascular disease in chronic renal failure, but the effect of different dialysis procedures on their plasma levels over time is poorly studied. The present prospective, randomized, cross-over trial tested dialysis efficacy and monitored pre-treatment pCS and IS concentrations in 15 patients on low-flux and high-flux hemodialysis and high-convective volume postdilution hemodiafiltration over six weeks each. Although hemodiafiltration achieved by far the highest toxin removal, only the mean total IS level was decreased at week three (16.6 ± 12.1 mg/L) compared to baseline (18.9 ± 13.0 mg/L, p = 0.027) and to low-flux dialysis (20.0 ± 12.7 mg/L, p = 0.021). At week six, the total IS concentration in hemodiafiltration reached the initial values again. Concentrations of free IS and free and total pCS remained unaltered. Highest beta₂-microglobulin elimination in hemodiafiltration (p < 0.001) led to a persistent decrease of the plasma levels at week three and six (each p < 0.001). In contrast, absent removal in low-flux dialysis resulted in rising beta₂-microglobulin concentrations (p < 0.001). In conclusion, this trial demonstrated that even large differences in instantaneous protein-bound toxin removal by current extracorporeal dialysis techniques may have only limited impact on IS and pCS plasma levels in the longer term. Full article

The transport and reaction phenomena that take place in multi-layered mixed-matrix membranes with activated carbon (AC) sorbents that are expected to improve extra-corporeal blood purification, are studied at the macroscopic scale. A model was developed that aims at the description of the removal efficiency of harmful uremic toxins from the blood in the presence of carbon-adsorptive particles and produces results that are aligned with the experimental data. The importance of the generally unknown kinetic rate constants of the association of toxins to albumin is investigated through sensitivity analysis. Matching with further experimental data allowed the extraction of vital kinetic rate constants for key uremic toxins such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS). Moreover, the effects of the plasma composition, as well as of the membrane loading with activated carbon, on the total removal of the protein-bound toxins are quantified and discussed. Full article