Contributions to nephrology最新文献

Sepsis and multiple organ failure (MOF) are characterized by multiple hemodynamic changes and imbalanced immune response of the patient. Oxiris is a highly adsorptive membrane with the ability to remove cytokines and endotoxins, as well as to perform renal replacement therapy. Here we describe the evolution from previous AN69 to the 3-in-1 Oxiris membrane, and review its characteristics and performance. In clinical practice, Oxiris showed consistent effects in mean arterial pressure recovery, a decrease in vasopressor needs, and reduction of the Sequential Organ Failure Assessment score. These results have been reproduced by several independent studies addressing both sepsis and, to a lesser extent, COVID-19 patients. In addition, more recent studies in sepsis showed improvements in MOF duration and the length of stay in the ICU, as well as some promising results regarding mortality. Finally, we review ongoing clinical trials and discuss its potential significance to clinical practice improvement and to further reinforce knowledge on the use of blood purification in sepsis and acute kidney injury.

Application of extracorporeal blood purification in children is increasing with the improvement of technology and the broadening of indications in critically ill patients. Furthermore, novel devices are being made available with a miniaturized design to be applicable to pediatric machines and circuits. Current literature in the pediatric setting is essentially based on case series and observational studies. Novel prospective uncontrolled databases are underway, and the interest is growing in children, since the potential indications for pediatric sepsis and other inflammatory conditions might rely on the enhanced mediator clearance warranted by these techniques. This review will describe the application of hemadsorption in children, the available cartridges, the clinical results available in the pediatric setting, and the potential future uses.

Hemoperfusion (HP) is an extracorporeal blood purification therapy that is used to remove poisons or drugs from the body. This chapter provides a brief overview of the technical aspects and the potential indications and limitations of HP, with the focus being on the use of HP for acute poisoning cases reported from January 1, 2000, to April 30, 2022.

Despite advances in dialysis technology, a high level of morbidity and mortality is still present in end-stage renal disease patients undergoing maintenance dialysis. This has been in great part correlated with accumulation of uremic toxins that cannot be adequately removed by classic dialysis membranes and techniques. Improvements have been made in enhancing both membrane permeability and convection rates as in the case for expanded hemodialysis (HD) and hemodiafiltration, but these techniques still present limitations or cannot be performed due to technical reasons. Considering the abovementioned limitations of current dialysis techniques, the additional use of adsorption as a solute removal mechanism may represent an interesting option. Recent studies have underlined the significant improvement in the levels of medium-large retention solutes and toxin-related symptoms using a combination of hemoperfusion with HD at least in a session per week. These studies need further confirmation, but they may represent the doorway to further improve patient's outcome in maintenance dialysis.

The mechanism of adsorption is regulated by various factors including the nature of the sorbent and the molecules involved in the adsorption process. The design of a device for adsorption therapies must fulfil specific requirements. The device should allow the use of the minimum amount of sorbent material sufficient to achieve safe and effective blood purification therapy. Each component of the device must respond to criteria of safety and function in order to maximize the efficiency of the cartridge. The design should be optimized to enable utilization of all the sorbent surface available for adsorption. The structure and packing of the sorbent particles should allow the even distribution of flow inside the cartridge and the avoidance of channeling phenomena and excessive resistance to flow. All these factors depend on specific governing laws such as the Kozeny-Carman equation and Darcy's law. The system must also consider blood viscosity and possible turbulent flows (Reynolds number). The final manufacturing process of a sorbent unit must also consider the dimensions and the cost, and the final performance after sterilization and storage.

With the growing prevalence of acute liver failure or acute-on-chronic liver failure, on the one hand, and the limited supply of liver organs for transplantation, on the other hand, it is critical to the design, validate, and implement devices that can provide extracorporeal liver support (ECLS) as the bridge to transplantation or potentially destination therapies. The number of attempts to generate ECLS devices has resulted in several options with various levels of impact on clinical outcomes. The described ECLS tools could be as simple as devices used for kidney replacement therapies (e.g., continuous kidney replacement therapy) to tools that employ albumin (e.g., Prometheus, single-pass albumin dialysis, or molecular adsorbent recirculating system), fresh frozen plasma (e.g., high-volume plasmapheresis), or hepatocytes (e.g., extracorporeal liver assist device with hepatocytes) to support failing liver functions, that is, metabolic or synthetic functions. This chapter describes the current landscape of ECLS devices and their associated evidence-based data.

Leptospirosis is the most common zoonosis frequently seen in the tropics and subtropics especially during the rainy season when humans wade in floods contaminated by the urine of infected rats in urban areas. Aside from direct toxicity of the leptospires, the role of an exuberant immune response to the pathogen leading to secondary organ damage has been recognized. Thus, our treatment protocol for patients with severe leptospirosis characterized by renal failure, acute liver injury, and lung hemorrhage now includes a short course of methylprednisolone and intravenous cyclophosphamide. In some patients, however, hemodynamic collapse and acute respiratory distress syndrome ensue, which may be due to the release of cytokines resulting from the dysregulated immune response. Blood purification in the form of hemoperfusion (HP) with neutral macroporous resin-adsorbing beads adsorbs cytokines and other inflammatory mediators leading to cardiovascular stability and stabilization of endothelial membranes. HP may be considered part of a multiorgan system therapeutic approach in diseases with reversible multiorgan failure that can lead to an improvement in patient survival.

Sepsis is a life-threatening syndrome initiated by a dysregulated host response to infection. Maladaptive inflammatory burst damages host tissues and causes organ dysfunction, the burden of which has been demonstrated as the paramount predictor of worse clinical outcomes. In this setting, septic shock represents the most lethal complication of sepsis and implies profound alterations of both the cardiovascular system and cellular metabolism with consequent high mortality rate. Although an increasing amount of evidence attempts to characterize this clinical condition, the complexity of multiple interconnections between underlying pathophysiological pathways requires further investigations. Accordingly, most therapeutic interventions remain purely supportive and should be integrated in light of the continuous organ cross-talk, in order to match a patient's specific needs. In this context, different organ supports may be combined to replace multiple organ dysfunctions through the application of sequential extracorporeal therapy in sepsis (SETS). In this chapter, we provide an overview of sepsis-induced organ dysfunction, focusing on the pathophysiological pathways that are triggered by endotoxin. Based on the need to apply specific blood purification techniques in specific time windows with different targets, we suggest a sequence of extracorporeal therapies. Accordingly, we reported the hypothesis that sepsis-induced organ dysfunction may benefit the most from SETS. Finally, we point out basic principles of this innovative approach and describe a multifunctional platform that allows SETS, in order to make clinicians aware of this new therapeutic frontier for critically ill patients.

A strong rationale supports the development of adsorption-based extracorporeal blood purification in conditions such as sepsis, acute kidney disease, uremia, and acute liver failure. The retention of compounds as a consequence of acute or chronic organ dysfunction might have detrimental effects. When a causative effect of an accumulated compound in a pathogenic condition is demonstrated, a rationale for the removal of this solute is also established. Adsorption is a mass transfer mechanism in which a solute chemically interacts with the surface of a solid structure (sorbent) and is removed from its solvent (i.e., blood or plasma). Traditional extracorporeal blood purification techniques utilize semipermeable membranes and depend mainly on diffusion and convection as mechanisms of mass transfer. Protein-bound solutes and water-soluble compounds with molecular weight above 25 kDa are scantly removed by either diffusive or convective clearances. In contrast, recently developed resins have demonstrated safety aligned with notable adsorptive capability, which enables the extraction of endotoxins, inflammatory mediators, and uremic toxins. The understanding of the kinetics of these elements and the improvement in patient selection are key factors to propel exploratory and confirmatory trials that ultimately will lead to the expected changes in clinical practice.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global emergency outbreak disease that devastatingly affected world public health and the economy. The pathogenesis of severe SARS-CoV-2 infection in humans has been linked to a strong immunological response that leads to a hyperinflammatory state, or "cytokine storm," which is a sepsis-like state resulting in capillary leakage, microvascular and macrovascular thrombosis, and multiple organ destruction. In recent years, there have been several case series and few randomized controlled trials studying the effectiveness and risk of various hemoperfusion techniques in the context of severe SARS-CoV-2 infection including HA330, CytoSorb, Polymyxin, oXiris, and Seraph 100 cartridges. Because inconsistencies exist between studies, there is currently no consensus regarding the use of hemoperfusion in patients with SARS-CoV-2 infection. Further well-designed research is needed to validate its potential clinical benefits and identify the timing and characteristics of patients who might benefit the most.