Contributions to Nephrology

Patients with severe thermal injury require urgent specialized care in burn units. These units assure good coordination of a bundle of care including fluid resuscitation, nutritional support, respiratory care, surgical care and wound care, infection prevention, and rehabilitation. When severely injured, burn patients present a systemic inflammatory response syndrome, associated with a dysregulated immune homeostasis. This complex host response exposes patients to prolonged hospitalization with suppressed immune function, increased susceptibility to secondary infections, longer organ support, and increased mortality...

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...

Liver failure in the intensive care unit (ICU), whether acute or acute-on-chronic, remains a serious condition with reduced functions, various metabolite and toxin accumulation in the systemic circulation, and a high mortality rate. While transplantation remains the treatment of choice, the lack of organ transplants necessitates finding alternative solutions. Within the last years, several therapies aiming to support liver function have been developed in order to serve as a bridge to liver transplantation or as replacement therapy, allowing regeneration of the injured liver...

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...

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...

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...

Inflammation plays a key role in the pathophysiology of organ dysfunction in the critically ill patients and is triggered by an overwhelming host response resulting in the overproduction of various cytokines. Regaining immune homeostasis over the dysregulated immune response through broad removal of cytokines using extracorporeal blood purification therapies has recently gained increasing attention. Nonetheless, many questions remain regarding the appropriate monitoring treatment, its potential risks, and side effects...

Extracorporeal circulation (ECC) such as cardiopulmonary bypass or extracorporeal membrane oxygenation (ECMO) may induce a complex activation of the immune system. To date, strategies to mitigate this activation have failed to translate into meaningful improvement of clinical outcomes. Hemoperfusion is a blood purification technique, which relies on mass separation by a solid agent (hemoadsorption). It can be performed by adding a cartridge filled with adsorptive sorbent in the extracorporeal circuit. These devices have the theoretical advantage to enable the removal of excess pro- and anti-inflammatory molecules...

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...

Major trauma care has seen significant improvements in early mortality, reflecting improvements in prehospital techniques for hemorrhage control and speed of access to specialized trauma centers. However, many patients then go on to die in the intensive care unit (ICU), and improvements in immediate trauma care are presenting intensivists with greater numbers of severely injured patients who might previously have died shortly after injury. It is theorized that, despite initial survival, these patients deteriorate due to massive release of damage associated molecular patterns (DAMPs) after traumatic and ischemic tissue injury...

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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...

In this chapter, anticoagulation treatments for adsorption techniques in continuous renal replacement therapy (CKRT) will be reviewed. Anticoagulation used with adsorption techniques is quite different than anticoagulation in classical CKRT with nonadsorptive therapies. Regional citrate anticoagulation (RCA) and unfractionated heparin (UFH) are the most common anticoagulation modalities for both nonselective adsorptive membranes - such as surface-treated acrylonitrile 69 membranes (AN69ST) and polymethylmethacrylate membranes - and selective adsorptive membranes such as AN69-oXiris...

In the fields of sepsis and systemic inflammation, endotoxin might be the most studied molecule since the term was coined by Richard Pfeiffer in 1892. Paradoxically measuring endotoxin in humans and finding an effective treatment for endotoxemia have remained challenging. While advances have been made in understanding the mechanisms of how this simple molecule can trigger an intense immune cascade, there is an ever growing need to develop better treatments. Studies measuring endotoxin levels in patients with septic shock have consistently demonstrated that there is a dose-response relationship between endotoxin levels and adverse outcomes...

Recent development in sorbent technology has spurred new interest in the potential of hemoperfusion (HP) in clinical conditions such as cytokine release syndromes and sepsis. Although the role of nonselective HP in such conditions requires solid evidence and more studies, the rationale for clinical application is clearly emerging. Greater biocompatibility and safety of the new sorbents may allow easy and safe application of HP in those conditions where the innate and the adaptive immune response of the individual appears to be dysregulated...

Despite recent technical advances in dialysis care over the past decades, the mortality rate of critically ill patients with acute kidney injury (AKI) requiring dialysis and of chronic kidney disease (CKD) remains unacceptably high. Several preclinical studies have increased our knowledge of the principal mechanisms involved in the pathophysiology of AKI and CKD. Additionally, the development of efficient and specific compensatory sorbent systems in renal replacement therapy to remove unwanted compounds has created the possibility to treat renal diseases and their underlying pathological triggers...

Direct hemoperfusion with the CytoSorb® adsorbent has experienced widespread use in several critical care settings including sepsis and multiorgan failure. The reported conditions of clinical usage and resulting outcomes vary considerably. The aim of the study was to provide an overview on current treatment recommendations based on the available clinical evidence. We performed a literature analysis using PubMed/MEDLINE and ClinicalTrials.gov to identify clinical data describing parameters of clinical usage of CytoSorb® in patients with septic shock (inclusion and exclusion criteria, starting, and dosing of treatment) and their impact on outcome...

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...

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...

The Jafron series of sorbent cartridges provides a comprehensive array of coated, highly biocompatible sorbent beads made of styrene-divinylbenzene copolymers. Such beads carry a mean diameter of 0.8 mm with a range from 0.60 to 1.18 mm. The maximal pore size of these coated beads and the volume of the cartridge vary according to the type of cartridge ranging between 50 Da and 60 kDa. The sorbents, the size of the cartridge, the volume of sorbent, and the pore size (which reaches 60 kDa with the HA330 cartridge) aim to take advantage of the principles of molecular adsorption in a variety of diseases from uremic toxin retention to poisoning and drug overdose, from kidney disease to liver failure, from acute respiratory distress syndrome to sepsis, from toxic skin injury to COVID-19...