Sepsis is one of the leading causes of morbidity and mortality worldwide. It is characterized by a dysregulated immune response to infections that results in life-threatening organ dysfunction and even death. Bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns (PAMPs), as well as damage-associated molecular patterns (DAMPs) released by host injured cells, are well-recognized triggers resulting in the elevation of both pro-inflammatory and anti-inflammatory cytokines. Understanding this complex pathophysiology has led to the development of therapeutic strategies aimed at restoring a balanced immune response by eliminating/deactivating these inflammatory mediators. Different extracorporeal techniques have been studied in recent years in the hope of maximizing the effect of renal replacement therapy in modulating the exaggerated host inflammatory response, including the use of high volume hemofiltration (HVHF), high cut-off (HCO) membranes, adsorption alone, and coupled plasma filtration adsorption (CPFA). These strategies are not widely utilized in practice, depending on resources and local expertise. The literature examining their use in septic patients is growing, but the evidence to support their use at this stage is considered of low level. Our aim is to provide a comprehensive overview of the technical aspects, clinical applications, and associated side effects of these techniques.

Extracorporeal blood purification techniques have emerged and evolved in the recent years as a potential therapy for the purpose of immunomodulation in acute conditions like sepsis. Understanding the extent of immune system dysregulation involved in the pathophysiology of these conditions, resulted in the development of such treatment strategies aiming at restoring a balanced inflammatory response. Beyond conventional continuous renal replacement therapy, high volume hemofiltration, high cut-off membranes, adsorption alone and coupled plasma filtration adsorption are well-described techniques in the literature. The evidence to support their routine use, however, is conflicting and insufficient at this stage. Despite the low-quality level of evidence in favor of utilizing these techniques, studies to further explore their effectiveness, safety, and potential novel applications, continue to evolve. Our review aims at focusing on adsorption therapy, particularly using the adsorption columns Cystosorb.

Adsorption is an extracorporeal technique utilized for blood purification. It complements convection and diffusion (the main modalities of solute removal). It involves the passage of blood (or plasma) through an adsorption cartridge, where solutes are removed by direct binding to the sorbent material. Over the years, new adsorption cartridges, with improved characteristics have been developed. Furthermore, the therapeutic applications of adsorption have expanded. These now involve the treatment of inflammatory conditions, chronic uremic symptoms, and autoimmune disease, in addition to intoxication, which was once considered the classical indication for adsorption therapy. HA130, HA230, and HA330 (Jafron, Zhuhai City, China) are among the widely used adsorption cartridges in China. There has been sufficient body of evidence to support their effectiveness and safety. In this review, we aim to highlight their main clinical applications.

NephroCheck® is the commercial name of a combined product of two urinary biomarkers, tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), expressed as [TIMP-2]·[IGFBP7], used to identify patients at high risk of acute kidney injury (AKI). AKI is a common and harmful complication especially in critically-ill patients, which can induce devastating short- and long-term outcomes. Over the past decade, numerous clinical studies have evaluated the utility of several biomarkers (e.g. neutrophil gelatinase-associated lipocalin, interleukin-18, liver-type fatty acid binding protein and kidney injury molecule-1, cystatin C) in the early diagnosis and risk stratification of AKI. Among all these biomarkers, [TIMP-2]·[IGFBP7] was confirmed to be superior in early detection of AKI, before the decrease of renal function is evident. In 2014, the US Food and Drug Administration permitted marketing of NephroCheck® (Astute Medical) (measuring urinary [TIMP-2]·[IGFBP7]) to determine if certain critically-ill patients are at risk of developing moderate to severe AKI. It has since been applied to clinical work in many hospitals of the United States and Europe to improve the diagnostic accuracy and outcomes of AKI patients. Now, more and more research is devoted to the evaluation of its application value, meaning and method in different clinical settings. In this review, we summarize the current research status of [TIMP-2]·[IGFBP7] and point out its future directions.

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Sepsis is the leading cause of acute kidney injury (AKI) in the intensive care unit (ICU). Septic AKI is a complex and multifactorial process that is incompletely understood. During sepsis, the disruption of the mucus membrane barrier, a shift in intestinal microbial flora, and microbial translocation may lead to systemic inflammation, which further alters host immune and metabolic homeostasis. This altered homeostasis may promote and potentiate the development of AKI. As part of this vicious cycle, when AKI develops, the clearance of inflammatory mediators and metabolic products is decreased. This will lead to further gut injury and breakdown in mucous membrane barriers. Thus, changes in the gut during sepsis can initiate and propagate septic AKI. This deleterious gut–kidney crosstalk may be a potential target for therapeutic maneuvers. This review analyses the underlying mechanisms in gut–kidney crosstalk in septic AKI.

Background:The use of an incremental peritoneal dialysis (PD) strategy in a large contemporary patient population has not been described.Objective:We report the use of this strategy in clinical practice, the prescriptions required, and the clearances achieved in a large center which has routinely used this approach for more than 10 years.Design:This is a cross-sectional observational study.Setting:A single large Canadian academic center.Patients:This study collected data on 124 prevalent PD patients at a single Canadian academic center.Methods and Measurements:The proportion of patients who achieve the clearance target on a low clearance or incremental PD prescription; the actual PD prescriptions and consequent total, peritoneal, and renal urea clearances [Kt/V] achieved; and patient and technique survival and peritonitis rate in comparison with national and international reports.Results:Of the 124 prevalent PD patients in this PD unit, 106 (86%) were achieving the Kt/V target, and of these, 54 (44% of all patients) were doing so using incremental PD prescriptions. Fifty of these incremental PD patients were using automated PD (APD) with either no day dwell (68%) or less than 7 days a week treatment (12%) or both (20%). Patient survival in our PD unit was not different from that reported in Canada as a whole. Peritonitis rates were better than internationally recommended standards.Limitations:This is an observational study with no randomized control group.Conclusions:Incremental PD is feasible in a contemporary PD population treated mainly with APD. Almost half of the patients were able to achieve clearance targets while receiving less onerous and less costly low clearance prescriptions. We suggest that incremental PD should be widely used as a cost-effective strategy in PD.

Background/Aims: The use of adsorption cartridges for hemoperfusion (HP) is rapidly evolving. For these devices, the potential induced cytotoxicity is an important issue. The aim of this study was to investigate potential in vitro cytotoxic effects of different sorbent cartridges, HA130, HA230, HA330, HA380 (Jafron, China), on U937 monocytes. Methods: Monocytes were exposed to the sorbent material in static and dynamic manners. In static test, cell medium samples were collected after 24 h of incubation in the cartridges. In dynamic test, HP modality has been carried out and samples at 30, 60, 90, and 120 min were collected. Results: Compared to control samples, there was no evidence of increased necrosis or apoptosis in monocytes exposed to the cartridges both in the static and dynamic tests. Conclusion: Our in vitro testing suggests that HA cartridges carry an optimal level of biocompatibility and their use in HP is not associated with adverse reactions or signs of cytotoxicity.