Expanding the potential therapeutic options of hemoperfusion in the era of improved sorbent biocompatibility

Article information

Kidney Res Clin Pract. 2023;42(3):298-311
Publication date (electronic) : 2023 March 29
doi : https://doi.org/10.23876/j.krcp.22.223
1Department of Nephrology, Ippokrateion University Hospital, Athens, Greece
2Service of Nephrology and Hypertension, Lausanne University Hospital, Lausanne, Switzerland
Correspondence: Aikaterini Damianaki Department of Nephrology, Ippokrateion University Hospital, Vasilissis Sofias 108, Athens 11527, Greece. E-mail: aikaterini.damianaki@chuv.ch
Received 2022 September 23; Revised 2022 November 22; Accepted 2022 November 23.

Abstract

Hemoperfusion has been considered a promising adjuvant treatment for chronic diseases and some acute states when specific removal of pathogenic factors from the bloodstream is desired. Over the years, advances in adsorption materials (e.g., new synthetic polymers, biomimetic coating, and matrixes with novel structures) have renewed scientific interest and expanded the potential therapeutic indications of hemoperfusion. There is growing evidence to suggest a prominent place for hemoperfusion as an adjuvant treatment in the setting of sepsis or severe coronavirus disease 2019 and as a therapeutic option for chronic complications associated with accumulated uremic toxins in patients with end-stage renal disease. This literature review will describe the principles, therapeutic perspectives, and the emerging role of hemoperfusion as a complementary therapy for patients with kidney disease.

Introduction

The removal of unwanted plasma solutes and pathogens can be life-saving under certain conditions, such as sepsis, intoxication, and organ failure. Thus, the unique ability of hemoperfusion (HP) to adsorb specific molecules with large molecular weight (MW) and/or a high protein-binding affinity could explain why HP has been allured as a promising treatment for several diseases [1].

Whereas poisoning was once considered the classical indication of HP, advances in sorbents’ biocompatibility and design have helped to expand its potential clinical indications to the treatment of inflammatory conditions (e.g., sepsis, pancreatitis, and hepatitis), autoimmune diseases, and chronic uremic symptoms [2].

The European Uremic Toxin Group classifies uremic toxins into three groups: small water-soluble toxins with an MW of <500 Da (e.g., urea and creatinine), middle molecules with an MW of ≥500 Da (e.g., parathyroid hormone [PTH], C-reactive protein, and β2-microglobulin [B2M]) that can be successfully removed by hemofiltration (HF) and high-flux hemodialysis (HD), and protein-bound solutes (e.g., homocysteine) which are not removed by classic HD or HF [3]. Moreover, as current dialysis techniques based on diffusion and convection show limitations due to membrane permeability characteristics [4], HP can be an attractive adjuvant modality for blood purification either alone or in combination with other renal-replacement therapies (RRTs). Besides, the high mortality rate attributed to cardiovascular disease and the outcomes of end-stage renal disease (ESRD) patients on HD have been correlated with blood levels of medium/large molecules insufficiently cleared by RRT [5].

Novel sorbents with greater biocompatibility and safety than before have renewed scientific interest in the broader implementation of HP [6]. Fig. 1 summarizes the advantages, disadvantages, and clinical conditions where HP can be considered.

Figure 1.

Overview of hemoperfusion technique.

HD, hemodialysis; COVID-19, coronavirus disease 2019; ESRD, end-stage renal disease.

Given the accumulation of encouraging data and the emerging new perspectives derived from research in HP as well as the current lack of consensus clinical guidelines, we aimed to conduct a literature review of the principles of HP, the evolution of sorbent materials, and the promising applications of HP in different clinical settings with a special focus on ESRD patients.

Principles of function and adsorption materials

According to the Consensus Conference on Biocompatibility, adsorption is the process of removing particles and toxins from the blood or plasma through their connection to the surface of the adsorbent, which lies in an extracorporeal purification machine [7].

Chemical and physical attraction forces are responsible for retaining the adsorbed molecules on the adsorbent. Physical forces include Van der Waals and hydrophobic interactions, whereas chemical interactions involve the formation of chemical bonds between the surface and the adsorbed species.

Adsorption materials can be found in nature or can be manufactured (e.g., synthetic polymers). Activated carbon produced from natural raw materials has shown a good adsorption capacity but poor biocompatibility [8,9]. Activated encapsulation technology or the use of activated carbon from other sources (resin-based) was considered for overcoming safety issues due mostly to the latter’s rough surface [10]. With these modifications and alternatives, however, the adsorption capacity was influenced [11].

Inorganic porous materials present some important advantages, such as reusability and pore size variability, but adverse effects have been reported with their use [1214]. Synthetic polymeric materials show remarkable functions, stability, and biocompatibility due to the tailor-made molecular design and/or surface modifications compared to natural polymeric materials. Notably, their low cost, hemocompatibility, and structure designability are their main advantages (Table 1) [15].

Summary of adsorbent types and their main advantages, disadvantages, and clinical indications

In general, adsorption materials can be found as granules, spheres, fibers, cylindrical pellets, flakes, and powders. They are solid particles with diameters ranging from 50 μm to 1.2 cm. Their surface area to volume ratio is extremely high, with the surface area ranging from 300 to 1,200 m2/g. Further classification of sorbents is based on their pore size, i.e., >500 Å (50 nm) (macroporous), 20 to 500 Å (mesoporous), and <20 Å (microporous).

Sorbents should also have favorable kinetics and transport properties. Isotherm equations and data from plotting curves known as adsorption isotherms during laboratory experiments provide information about the amount of sorbent required to remove a given amount of solute (Fig. 2) [1]. Moreover, packing sorbent particles into a cartridge requires a tortuous pathway (sorbent bed) through which blood or fluid must flow and be distributed uniformly. The mechanisms of solute adsorption in porous media include: 1) the external (interphase) mass transfer of the solute by convection from the bulk fluid and by diffusion through a thin film or boundary layer to the outer surface of the sorbent, 2) the internal (intra-phase) mass transfer of the solute by convection from the outer phase of the sorbent into the internal porous structure, and 3) surface diffusion along the surface of the internal pores and adsorption of the solute onto the porous surface (Fig. 3) [16].

Figure 2.

Example of adsorption isotherm graph.

Adsorption increases steadily until it reaches equilibrium, which is when the concentration of the marker solute at the outlet of the unit is equal to the concentration at the inlet.

Ps, saturation pressure.

Figure 3.

Mechanism of solute adsorption in porous media.

Mechanisms of mass transport from the bulk solution to the sorbent surface. (A) External (interphase) mass transfer of the solute by convection from the bulk fluid by diffusion through a thin film of boundary layer to the outer surface of the sorbent. (B) Internal (intra-phase) mass transfer of the solute by pore convection from the outer surface of the adsorbent to the inner surface of the internal porous structure. (C) Surface diffusion along the porous surface and adsorption of the solute onto the porous surface. Reproduced from Clark et al. [16] with permission of Karger Publishers.

Biocompatibility

The ideal sorbent material for extracorporeal therapies is one that is biocompatible. Moreover, it should be characterized by hardness and mechanical strength to prevent crushing and erosion and to avoid any release of fragments into the systemic circulation. Additionally, since the blood is exposed to a larger surface in this context compared to other extracorporeal therapies, any cytotoxic reaction and immune system activation—clinically identifiable with the onset of rashes, shivers, leukopenia, and thrombocytopenia—must be prevented [17].

Therefore, surface coating is an attractive method to increase biocompatibility. Coating materials such as cellulose nitrate, albumin-collodion, cellulose acetate, and polyamide were initially evaluated by Chang [18], whereas hydrogel was investigated by Andrade et al. [19]. Later on, various polymeric systems were developed to form stable protective coatings with better performances.

Anti-adhesion properties are also important for biocompatibility since the contact of blood with an artificial surface triggers a number of processes, including protein and cell adsorption and platelets’ adhesion to the artificial surface. Thus, anti-adhesion modifications and surface coating using new materials like zwitterionic groups have received increasing interest [20]. Indeed, zwitterionic materials are highly resistant to non-specific protein adsorption, bacterial adhesion, and biofilm formation [21].

Selective targeting

Selective targeting of a key molecule as an endotoxin has promoted the concept of surface grafting. Besides, in complex biological media such as blood, they will always exist molecules of different origins that compete for the chemical adsorption site against the target molecules. By immobilizing a molecule with a specific affinity for the target molecule on the surface, a high affinity is obtained, mainly via a combination of electrostatic and hydrophobic interactions plus steric complementarity of both molecules rather than a covalent chemical bond formation [22].

Polymyxin B, an antibiotic derived from Bacillus polymyxa that binds and neutralizes endotoxin (an outer membrane component of gram-negative bacteria), and protein A, which binds anthrax toxin (a specific exotoxin secreted by virulent strains of the bacterium Bacillus anthracis), are typical applications of the surface grafting concept in cases of sepsis [23,24]. Except for antibiotics, other ligands (e.g., amino acids) have also been used [25]. Technological achievements in the genomic area have inspired the use of grafted nucleic acid-based ligands on adsorbents for the treatment of patients with systemic lupus erythematosus and hepatitis B [26,27]. Synthetic ligands also exhibit resistance to biological degradation and similar selectivity [28]. Finally, computation simulation has enabled the design of affinity ligands based on the structure of Asp-Phe-Leu-Ala-Glu (DE5), a sequence of toxic peptides frequently found in uremic patients [29].

Technical aspects of hemoperfusion

HP alone does not achieve sufficient removal of small uremic toxins and fluid balance; however, when combined with other HD techniques, a synergistic effect can be obtained [6].

In HP, the cartridge is placed in direct contact with the patient’s blood, with the basic requirements being an HP cartridge, double lumen catheter, vascular access, and an anticoagulant (heparin or citrate) [30]. HP is effective in removing uncharged molecules through competitive binding, especially those that are significantly plasma protein-bound and lipophilic. Indeed, HP targets molecules that tend to be more difficult to remove with conventional HD or with continuous RRTs (CRRT) and has the capacity to remove molecules with MW up to 30,000 Da depending on the characteristics of the sorbent material [31]. When combined with HD/CRRT, the sorbent can be placed before or after the dialyzer and enhance the removal of middle molecules that are not sufficiently removed by HD, such as B2M [32].

In the process of plasma filtration adsorption, plasma is first separated from the whole blood and circulates through the sorbent [33], then is returned to the whole blood, which can be subjected to HD or CRRT in order to expand the clearance of small solutes such as urea and creatinine. In this case, the use of both methods maximizes solutes’ removal [34].

In double plasma filtration molecular adsorption system, different cartridges exhibiting specific characteristics can be placed in the plasma filtration circuit [35]. Finally, HP can be combined with extracorporeal membrane oxygenation [36].

Potential clinical applications of hemoperfusion and ongoing trials

Poisoning

Extracorporeal therapies for drug or chemical intoxication are indicated when there is life-threatening toxicity, an inadequate response to standard supportive measures, or the poison’s endogenous clearance is <4 mL/min/kg and the poison’s volume distribution is <1–2 L/kg [37].

Nowadays, the use of high-flux and high-efficiency dialyzers and the higher blood flow rates achieved, have established intermittent HD as the preeminent extracorporeal modality for poisoning. Moreover, HD is easily accessible; it removes poisons rapidly and simultaneously corrects any electrolyte and acid-base disorders [38]. In contrast, HP requires greater systemic anticoagulation; flows that do not exceed 350 mL/min so as to avoid the risk of hemolysis; and nonselectively adsorbs platelets, calcium, glucose, and white blood cells [39,40]. The higher cost and the need to replace the cartridge every 2 hours due to saturation are also important disadvantages of HP [41]. Finally, for some metals like lithium and alcohols (e.g., methanol, ethylene glycol), HP is not indicated due to less efficiency [42,43].

While HP use for poisoning has declined to roughly 1% of HD utilization in the United States [44], HP seems to be more effective than HD for paraquat poisoning [45]. HP achieves enhanced clearance of paraquat, leading to higher survival rates compared to high-flux HD [46]. With paraquat poisoning being an important concern mostly in Asia, current recommendations do not mention the use of extracorporeal treatment for it [37].

Currently, the strongly recommended method by the EXTRIP (Extracorporeal Treatments in Poisoning) group for the removal of most drugs is intermittent HD (https://www.extrip-workgroup.org/recommendations). In some cases, HP is an alternative option (1C or 1D) when HD cannot be performed (Table 2).

List of drugs and the recommended extracorporeal therapy in case of acute poisoning

Sepsis

CRRT methods are widely used due to their capacity to retain body fluid balance and to correct electrolytic and acid-base imbalances in patients with sepsis and acute kidney injury (AKI). However, the removal of proinflammatory cytokines and complement fragments that promote kidney dysfunction and aggravate multiorgan dysfunction in the setting of septic shock is limited due to the limited permeability of the membranes [47]. Consequently, the use of high-flux HF and/or high cut-off membranes has been encouraged due to their removal capacity reaching up to 65 kDa. Unfortunately, their main disadvantage is the concomitant removal of important amounts of albumin. Therefore, HP and the design of biocompatible cartridges with the potential for customizing the target solutes have led to the increasing application of adsorption in sepsis and other inflammatory states such as coronavirus disease 2019 (COVID-19) (Table 3).

Summary of characteristics and main results of the most frequently used HP filters in the field of sepsis and COVID-19 infection

With selective HP being an alluring approach for removing circulating endotoxin and theoretically preventing the biological cascade in sepsis, research had focused on the use of polymyxin-bound membranes. Besides, antiendotoxin drug therapies and intravenous polymyxin B have failed to prove a clinical benefit [48]. Therefore, direct HP with a polymyxin device (Toraymyxin; Today Industries Ltd.) was initially introduced and approved in Japan as an adjuvant sepsis therapy [49]. Later on, its use was expanded to other countries. Several randomized trials have provided conflicting results on the clinical benefit of polymyxin B in terms of mortality, hemodynamic parameters, and respiratory function of patients with septic shock due to an abdominal cause compared to conventional care [5052]. Currently, the TIGRIS study (NCT03901807), a prospective, multicenter, randomized open-label trial, is investigating the effects of standard medical care plus polymyxin-based HP versus the standard care of treatment.

Regarding nonselective HP, extracorporeal cytokine adsorption with the CytoSorb cartridge (CytoSorbents Corporation) has been investigated in case series and small comparative studies [5355]. CytoSorb consists of specially designed polymers with large surfaces, high flow, and low resistance. It is indicated for clinical situations with high plasma concentrations of cytokines. CytoSorb binds cytokines 10 to 50 kDa in size, with a removal rate of >90% to 95% [56]. However, in a multicenter randomized trial comparing conventional care with CytoSorb in ventilated patients with sepsis and either acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), no significant differences in interleukin (IL)-6 concentration were observed [57]. In a recent randomized controlled trial (RCT; the REMOVE trial), the authors failed to demonstrate a reduction in postoperative organ dysfunction or 30-day mortality with intraoperative use of CytoSorb in patients undergoing cardiac surgery for infective endocarditis. Even though CytoSorb achieved a lower level of plasma key cytokines, no clinical benefit was obtained [58].

HP with the Jafron HA cartridges (Jafron Biomedical Company) has also been tested in acute respiratory failure caused by sepsis, with prominent results concerning hemodynamic parameters, respiratory function, and mortality within 28 days of hospitalization [59]. The HA 330 cartridge has an electrically porous resin that specifically removes cytokines, complements, and other endotoxins with MWs of 10 to 60 kDa. HA 330-based HP was studied in multiple cohorts in the context of inflammatory conditions such as sepsis, ALI, hepatitis, and pancreatitis [2]. In a small nonrandomized study, intensive care unit (ICU) mortality and length of ICU stay were found to be better in septic patients receiving HA 330-based HP compared to those given standard therapy, albeit with no effect on mortality [60]. Encouraging results come from a case series of children with sepsis and underlying hematological disorders receiving HA 330-based HP as an adjunctive treatment to counterbalance the cytokine storm [61]. In another study, patients with ALI induced by extrapulmonary sepsis were randomized to HA 330-based HP or standard therapy. In the HP group, significant reductions in the duration of mechanical ventilation and ICU stay and the ICU mortality rate were observed. Improved respiration parameters were also observed and correlated with the significant removal of inflammatory cytokines (tumor necrosis factor [TNF] and IL-1). In a recent study by Chu et al. [62], the combination of the same cartridge with pulse high-volume HF in patients experiencing septic shock led to beneficial effects on cardiovascular physiology and greater decreases in IL-6, IL-10, and TNF-α concentration when compared to patients who received continuous venous-venous HF.

Finally, the AN69-based oXiris membrane (Baxter Inc.), which is a heparin-grafted membrane specifically designed for cytokine and endotoxin adsorption, alongside RRT, presents three layers: 1) AN69 copolymer hydrogel structure that adsorbs cytokines and removes solutes via convection through membrane pores, 2) a multilayer structure of polyethyleneimine that adsorbs endotoxin and offers better biocompatibility, and 3) a heparin graft that reduces local thrombogenicity [63]. In vitro comparison of oXiris with Toraymyxin and CytoSorb revealed similar efficacies in lipopolysaccharide clearance and inflammatory mediator clearance, respectively [64]. However, there are a limited number of studies to support its action in septic shock compared to the above-mentioned products [6567].

Viral infections, including severe acute respiratory syndrome coronavirus 2

Uncontrolled cytokine response was considered the hallmark of severe COVID-19 during the first months of the pandemic [68]. Several extracorporeal blood-purification techniques have been used in COVID-19 patients to restore “immune homeostasis” by removing inflammatory molecules [69].

Recently, experts’ recommendations state that, in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and cytokine release syndrome, cytokine-removal strategies should be reserved for COVID-19 patients with evidence of high levels of circulating cytokines like IL-6 and IL-8, a biochemically determined inflammatory status, a high SOFA (Sequential Organ Failure Assessment) score, clinical symptoms of hemodynamic instability requiring vasopressors, and initial signs of immune dysregulation or coagulation disorders [69]. Polymyxin-based HP is indicated in the early phase for suspected sepsis (indicated by a high procalcitonin level and/or positive bacterial culture) or an elevated endotoxin level proven by activity assay. If HP is indicated for cytokine removal, sessions with CytoSorb or HA 380 might follow.

In fact, the U.S. Food and Drug Administration (FDA) has approved four blood-purification devices to treat COVID-19, including 1) CytoSorb, 2) the Seraph 100 Microbind Affinity Blood Filter (ExThera Medical Corporation), 3) the oXiris Filter, and 4) the Spectra Optia Apheresis System (Terumo BCT) [70].

The first case of CytoSorb use in conjunction with CRRT in a critically ill patient with COVID-19 was reported by Rizvi et al. [71], underlining a plausible contribution to early improvement in inflammatory markers. Other case-control and retrospective studies followed, highlighting a potentially beneficial role of adjuvant HP with CytoSorb in the early phase of COVID-19 in terms of cytokine reductions (mainly IL-6 levels), a better clinical course with less need for vasoactive agents, and the improvement of respiratory distress. However, data on mortality rates were inconsistent [7277]. Indeed, in a recent prospective, randomized pilot study with 50 COVID-19 patients receiving CytoSorb for 3 to 7 days or standard therapy, HP did not improve the resolution of vasoplegic shock (primary outcome) or the predefined secondary endpoints, which included mortality, IL-6 concentration, and catecholamine requirement [78]. Ongoing randomized trials and a large registry of CytoSorb therapy in COVID-19 ICU patients (NCT04391920) aim to enrich the current literature regarding the role of CytoSorb as a potential therapy in severe COVID-19 [70].

HP with the Seraph 100 Microbind Affinity Blood Filter, a biomimetic adsorber that has been shown to bind pathogens, including SARS-CoV-2, from the blood using ultra-high MW adsorptive beads [79], received Emergency Use Authorization for severe COVID-19 from the FDA. Olson et al. [80] were the first to report its use in COVID-19 patients with ARDS and septic shock who required mechanical ventilation. Rapid improvement in vasopressor needs, overall circulatory dysfunction as well as C-reactive protein and IL-6 levels were noticed following the initiation of HP. Similar results were documented by Sandoval et al. [81] who used Seraph 100 in four elderly, multimorbid ESRD patients on HD with severe COVID-19. Data from the COSA (COVID-19 patients treated with the Seraph 100 Microbind Affinity filter) registry support that Seraph 100 treatment is easy to deploy either as a stand-alone HP treatment or in combination with RRT. The observed mortality rate was lower than that calculated by established scores, but the data are limited due to the lack of a control group [82]. Initial data from an observational retrospective study (PURIFY-OBS-1; NCT04606498) suggest improvements in the survival of severely ill COVID-19 patients treated with Seraph 100.

Evidence of significant reductions in inflammatory markers and improved hemodynamics, organ function, and clinical outcomes with oXiris comes mostly from case series, the oXirisNet registry, and small observational studies [8385]. An RCT (oXAKI-COV Study; NCT04597034) is ongoing and aims to demonstrate the clinical efficacy of AN69-oXiris compared to the AN69 standard membrane in decreasing vasopressor requirements to sustain a stable mean arterial pressure in critically ill patients with COVID-19 and AKI requiring CRRT.

Finally, the Spectra Optia Apheresis System provides therapeutic apheresis in combination with HP with the Depuro D2000 adsorption cartridge. The Depuro D2000 cartridge is composed of activated uncoated coconut shell charcoal and the non-ionic resins Amberlite XAD-7HP and Amberchrom GC300C, and its placement downstream in the apheresis circuit allows for cytokine removal with subsequent return of the treated plasma to the patient. Its use as a rescue therapy for cardiogenic shock due to stress-cardiomyopathy in severe COVID-19 has been reported only in a single patient by Faqihi et al. [86]. An ongoing large multicenter single-arm clinical trial (Plasma Adsorption in Patients With Confirmed COVID-19; NCT04358003) of the United States is expected to provide information about the effects of the D2000 cartridge with the Optia protocol on morbidity and mortality rates of COVID-19 patients admitted to the ICU.

Maximizing toxin removal and clinical benefits in patients with end-stage renal disease

ESRD has been increasingly recognized as an inflammatory state with protein-bound uremic toxins (PBUTs) and middle molecules like B2M being key factors and inducing various cardiovascular complications. Therefore there is a rationale for the increasing research on synergic approaches that combine HP with other dialytic techniques to achieve complementary elimination of metabolites and effectively prevent and treat complications and improve clinical outcomes [6,87].

Regarding overall survival, a systematic review and meta-analysis showed that the combination of HD with HP improves survival rates [88].

Important ameliorations of blood pressure—even in dialysis patients with refractory hypertension—and left ventricular mass index, reduced dosages of epoetin, and higher hemoglobin levels, have been reported when HD with HP are combined compared to HD alone [8991]. Considering the more pronounced decrease in levels of myocardial enzymes associated with the combination of HP and HD, it was speculated that their concurrent use can lighten the cardiovascular burden and protect the myocardium [92]. Besides, the improvement of microinflammatory indicators associated with the combination of these therapies could partially explain the lower incidence of cardiocerebrovascular events and the improvement of anemia in patients who had received both HP and HD treatment [93].

Along the same lines, in a study by Raine et al. [94], apart from the greater reduction in inflammation markers, an important improvement in the indices of nutritional status occurred in the HD plus HP group.

Greater benefits in terms of B2M and PTH reductions have been shown by several studies when HP and HD were combined. Hence, there are potential to improve secondary hyperparathyroidism, pruritus, and dialysis-related amyloidosis [9597].

Interestingly, based on the reported relationship between the intestinal environment and renal disease, HP combined with dialysis showed encouraging results with respect to the potential improvement of microbiota disorders. Indeed, significantly higher levels of beneficial bacteria like Lactobacillus acidophilus and lower levels of harmful bacteria such as Escherichia coli were reported in colony distributions of patients receiving HP combined with HD plus hemodiafiltration compared to patients receiving HD plus HF [98]. Research is now focusing on promising sorbent materials—such as a divinylbenzene sorbent coated with polyvinylpyrrolidone (DVB-PVP) and cellulose with hexadecyl chains—which show a high adsorption ability of PBUTs or hydrophobic cytokines. A synergistic effect on the reduction of PBUTs was recently demonstrated during HD therapy combined with DVB-PVP resins and symbiotic formulation [99].

Moreover, improved sleep disturbance and sleep efficiency accompanied by an increase in nocturnal melatonin levels were reported with HP therapy (1–2 times/wk) for 2 years [100].

Finally, there is some evidence that the combination of HP with HD can improve the life quality of ESRD patients [97,101]. Symptoms like skin itching, fatigue, sleep quality, and sexual function were significantly improved by adding HP, probably due to the greater clearance of middle and large molecular toxins such as PTH and B2M [88].

Experimental indications of sorbent use in systemic diseases with kidney involvement

Some interesting results have arisen from case series of patients with systemic autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, and vasculitis with and without renal involvement [102,103]. Improvements in renal function and dialysis independence following HP sessions in combination with chemotherapy have also been reported in a patient with cast nephropathy [104]. Finally, AKI can occur as a side effect of medications used in autoimmune disease; thus, HP could also be of value in this context. A recent small case series of patients with high-dose methotrexate-induced AKI showed a possibly positive effect of using charcoal HP as a rescue therapy until glucarpidase is available [105].

Conclusion

Whereas HP was once only indicated for treating poisoning from certain substances, emerging evidence suggests that other indications might be also considered. Advances in the biocompatibility of new cartridges and the selective removal of key molecules in different clinical settings and diseases like sepsis, hepatitis, and SARS-CoV-2 infection have been considered as the triggering force in that direction. With the increasing research interest in the removal of PBUTs and their involvement in CKD-related systemic complications, HP is also regaining its place as a vital accessory to dialysis treatment.

Despite this progress, current clinical use of HP remains limited, with possible reasons including the cost of performance, local practice or physician preference, a lack of consensus clinical guidelines and established indications for HP, and the absence of consistent data derived from RCTs.

In conclusion, the role of HP remains a point of discussion until its clinical effectiveness can be verified by further positive RCTs. Although in this era of disease-targeting treatments new indications are being investigated, efforts to better evaluate the applicability of HP and to shed light on the role of HP in current clinical practice are needed.

Notes

Conflicts of interest

All authors have no conflicts of interest to declare.

Data sharing statement

The data presented in this study are available on request from the corresponding author.

Authors’ contributions

Conceptualization: All authors

Investigation: AD, ES, ZA

Supervision: AD, DP

Writing–original draft: AD, ES, ZA

Writing–review & editing: All authors

All authors read and approved the final manuscript.

References

1. Ronco C, Bellomo R. Hemoperfusion: technical aspects and state of the art. Crit Care 2022;26:135.
2. Ankawi G, Fan W, Pomarè Montin D, et al. A new series of sorbent devices for multiple clinical purposes: current evidence and future directions. Blood Purif 2019;47:94–100.
3. Vanholder R, De Smet R, Glorieux G, et al. Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int 2003;63:1934–1943.
4. Ankawi G, Neri M, Zhang J, Breglia A, Ricci Z, Ronco C. Extracorporeal techniques for the treatment of critically ill patients with sepsis beyond conventional blood purification therapy: the promises and the pitfalls. Crit Care 2018;22:262.
5. Moradi H, Sica DA, Kalantar-Zadeh K. Cardiovascular burden associated with uremic toxins in patients with chronic kidney disease. Am J Nephrol 2013;38:136–148.
6. Magnani S, Atti M. Uremic toxins and blood purification: a review of current evidence and future perspectives. Toxins (Basel) 2021;13:246.
7. Gurland HJ, Davison AM, Bonomini V, et al. Definitions and terminology in biocompatibility. Nephrol Dial Transplant 1994;9:4–10.
8. Yatzidis H. A convenient hemoperfusion microapparatus over charcoal for the treatment of endogenous and exogenous intoxification: Its use as an effective artificial kidney. Proc Eur Dial Transpl Assoc 1964;1:83–87.
9. Radomski A, Jurasz P, Alonso-Escolano D, et al. Nanoparticle-induced platelet aggregation and vascular thrombosis. Br J Pharmacol 2005;146:882–893.
10. Przepiórski J, Tryba B, Morawski AW. Adsorption of carbon dioxide on phenolic resin-based carbon spheres. Appl Surf Sci 2002;196:296–300.
11. Miao J, Zhang F, Takieddin M, Mousa S, Linhardt RJ. Adsorption of doxorubicin on poly(methyl methacrylate)-chitosan-heparin-coated activated carbon beads. Langmuir 2012;28:4396–4403.
12. Tang T, Li X, Xu Y, et al. Bilirubin adsorption on amine/methyl bifunctionalized SBA-15 with platelet morphology. Colloids Surf B Biointerfaces 2011;84:571–578.
13. Murugavel S. In vitro studies of the efficacy of reversed phase silica gel as a sorbent for hemo- and plasmaperfusion. J Toxicol Clin Toxicol 1992;30:69–82.
14. Zhang LX, Zhu M, Guo LM, Li L, Shi JL. Bilirubin adsorption property of mesoporous silica and amine-grafted mesoporous silica. Nano-Micro Lett 2009;1:14–18.
15. Dou W, Wang J, Yao Z, Xiao W, Huang M, Zhang L. A critical review of hemoperfusion adsorbents: materials, functionalization and matrix structure selection. Mater Adv 2022;3:918–930.
16. Clark WR, Ferrari F, La Manna G, Ronco C. Extracorporeal sorbent technologies: basic concepts and clinical application. Contrib Nephrol 2017;190:43–57.
17. Pond SM. Extracorporeal techniques in the treatment of poisoned patients. Med J Aust 1991;154:617–622.
18. Chang TM. Microcapsule artificial kidney: including updated preparative procedures and properties. Kidney Int Suppl 1976;(7):S218–S224.
19. Andrade JD, Kunitomo K, Van Wagenen R, Kastigir B, Gough D, Kolff WJ. Coated adsorbents for direct blood perfusion: HEMA-activated carbon. Trans Am Soc Artif Intern Organs 1971;17:222–228.
20. Cai N, Li Q, Zhang J, et al. Antifouling zwitterionic hydrogel coating improves hemocompatibility of activated carbon hemoadsorbent. J Colloid Interface Sci 2017;503:168–177.
21. Jiang S, Cao Z. Ultralow-fouling, functionalizable, and hydrolysable zwitterionic materials and their derivatives for biological applications. Adv Mater 2010;22:920–932.
22. Mikhalovsky SV. Emerging technologies in extracorporeal treatment: focus on adsorption. Perfusion 2003;18 Suppl 1:47–54.
23. Ingavle GC, Baillie LW, Zheng Y, et al. Affinity binding of antibodies to supermacroporous cryogel adsorbents with immobilized protein A for removal of anthrax toxin protective antigen. Biomaterials 2015;50:140–153.
24. Terayama T, Yamakawa K, Umemura Y, Aihara M, Fujimi S. Polymyxin B hemoperfusion for sepsis and septic shock: a systematic review and meta-analysis. Surg Infect (Larchmt) 2017;18:225–233.
25. Wu S, Duan B, Zeng X, et al. Construction of blood compatible lysine-immobilized chitin/carbon nanotube microspheres and potential applications for blood purified therapy. J Mater Chem B 2017;5:2952–2963.
26. Yang Y, Yu YT, Song JC, et al. A new DNA immune adsorbent for hemoperfusion in SLE therapy: a clinical trial. Artif Organs 1988;12:444–446.
27. Zheng H, Lang Y, Yu J, Han Z, Chen B, Wang Y. Affinity binding of aptamers to agarose with DNA tetrahedron for removal of hepatitis B virus surface antigen. Colloids Surf B Biointerfaces 2019;178:80–86.
28. Zhao R, Li Y, Li X, et al. Facile hydrothermal synthesis of branched polyethylenimine grafted electrospun polyacrylonitrile fiber membrane as a highly efficient and reusable bilirubin adsorbent in hemoperfusion. J Colloid Interface Sci 2018;514:675–685.
29. Qiao Y, Zhao J, Li P, et al. Adsorbents with high selectivity for uremic middle molecular peptides containing the Asp-Phe-Leu-Ala-Glu sequence. Langmuir 2010;26:7181–7187.
30. Ronco C, Bordoni V, Levin NW. Adsorbents: from basic structure to clinical application. Contrib Nephrol 2002;(137):158–164.
31. Clark WR, Gao D, Lorenzin A, Ronco C. Membranes and sorbents. Contrib Nephrol 2018;194:70–79.
32. Li Z, Wang G, Zhen G, Zhang Y, Liu J, Liu S. Effects of hemodialysis combined with hemoperfusion on severe acute pancreatitis. Turk J Gastroenterol 2018;29:198–202.
33. La Manna G, Donati G. Coupled plasma filtration adsorption: a multipurpose extracorporeal detoxification therapy. Blood Purif 2018;46:228–238.
34. Redant S, De Bels D, Ismaili K, Honoré PM. Membrane-based therapeutic plasma exchange in intensive care. Blood Purif 2021;50:290–297.
35. Wu M, Zhang H, Huang Y, Wu W, Huang J, Yan D. Efficiency of double plasma molecular absorption system on the acute severe cholestatic hepatitis. Blood Purif 2021;50:876–882.
36. Rodeia SC, Martins FL, Fortuna P, Bento L. Cytokine adsorption therapy during extracorporeal membrane oxygenation in adult patients with COVID-19. Blood Purif 2022;51:791–798.
37. Ghannoum M, Hoffman RS, Gosselin S, Nolin TD, Lavergne V, Roberts DM. Use of extracorporeal treatments in the management of poisonings. Kidney Int 2018;94:682–688.
38. King JD, Kern MH, Jaar BG. Extracorporeal removal of poisons and toxins. Clin J Am Soc Nephrol 2019;14:1408–1415.
39. Falkenhagen D, Gottschall S, Esther G, Courtney JM, Klinkmann H. In vitro assessment of charcoal and resin hemoadsorbents. Contrib Nephrol 1982;29:23–33.
40. Rahman MH, Haqqie SS, McGoldrick MD. Acute hemolysis with acute renal failure in a patient with valproic acid poisoning treated with charcoal hemoperfusion. Hemodial Int 2006;10:256–259.
41. Mydlík M, Derzsiová K, Bucek J, Horký K, Jarcuska J, Takác M. Use of charcoal haemoperfusion in 55 acute poisonings. Life Support Syst 1983;1 Suppl 1:53–56.
42. Favin FD, Klein-Schwartz W, Oderda GM, Rose SR. In vitro study of lithium carbonate adsorption by activated charcoal. J Toxicol Clin Toxicol 1988;26:443–450.
43. Roberts DM, Yates C, Megarbane B, et al. Recommendations for the role of extracorporeal treatments in the management of acute methanol poisoning: a systematic review and consensus statement. Crit Care Med 2015;43:461–472.
44. Ghannoum M, Lavergne V, Gosselin S, et al. Practice trends in the use of extracorporeal treatments for poisoning in four countries. Semin Dial 2016;29:71–80.
45. Hong SY, Yang JO, Lee EY, Kim SH. Effect of haemoperfusion on plasma paraquat concentration in vitro and in vivo. Toxicol Ind Health 2003;19:17–23.
46. Rao R, Bhat R, Pathadka S, Chenji SK, Dsouza S. Golden hours in severe paraquat poisoning: the role of early haemoperfusion therapy. J Clin Diagn Res 2017;11:OC06–OC08.
47. Dellepiane S, Marengo M, Cantaluppi V. Detrimental cross-talk between sepsis and acute kidney injury: new pathogenic mechanisms, early biomarkers and targeted therapies. Crit Care 2016;20:61.
48. Cruz DN, Perazella MA, Bellomo R, et al. Effectiveness of polymyxin B-immobilized fiber column in sepsis: a systematic review. Crit Care 2007;11:R47.
49. Shimizu T, Miyake T, Tani M. History and current status of polymyxin B-immobilized fiber column for treatment of severe sepsis and septic shock. Ann Gastroenterol Surg 2017;1:105–113.
50. Cruz DN, Antonelli M, Fumagalli R, et al. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA 2009;301:2445–2452.
51. Payen DM, Guilhot J, Launey Y, et al. Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial. Intensive Care Med 2015;41:975–984.
52. Dellinger RP, Bagshaw SM, Antonelli M, et al. Effect of targeted polymyxin B hemoperfusion on 28-day mortality in patients with septic shock and elevated endotoxin level: the EUPHRATES randomized clinical trial. JAMA 2018;320:1455–1463.
53. Boss K, Jahn M, Wendt D, et al. Extracorporeal cytokine adsorption: significant reduction of catecholamine requirement in patients with AKI and septic shock after cardiac surgery. PLoS One 2021;16e0246299.
54. Paul R, Sathe P, Kumar S, Prasad S, Aleem M, Sakhalvalkar P. Multicentered prospective investigator initiated study to evaluate the clinical outcomes with extracorporeal cytokine adsorption device (CytoSorb) in patients with sepsis and septic shock. World J Crit Care Med 2021;10:22–34.
55. Brouwer WP, Duran S, Kuijper M, Ince C. Hemoadsorption with CytoSorb shows a decreased observed versus expected 28-day all-cause mortality in ICU patients with septic shock: a propensity-score-weighted retrospective study. Crit Care 2019;23:317.
56. Taniguchi T. Cytokine adsorbing columns. Contrib Nephrol 2010;166:134–141.
57. Schädler D, Pausch C, Heise D, et al. The effect of a novel extracorporeal cytokine hemoadsorption device on IL-6 elimination in septic patients: a randomized controlled trial. PLoS One 2017;12e0187015.
58. Diab M, Lehmann T, Bothe W, et al. Cytokine hemoadsorption during cardiac surgery versus standard surgical care for infective endocarditis (REMOVE): results from a multicenter randomized controlled trial. Circulation 2022;145:959–968.
59. Huang Z, Wang SR, Yang ZL, Liu JY. Effect on extrapulmonary sepsis-induced acute lung injury by hemoperfusion with neutral microporous resin column. Ther Apher Dial 2013;17:454–461.
60. Huang Z, Wang SR, Su W, Liu JY. Removal of humoral mediators and the effect on the survival of septic patients by hemoperfusion with neutral microporous resin column. Ther Apher Dial 2010;14:596–602.
61. Sazonov V, Abylkassov R, Tobylbayeva Z, Saparov A, Mironova O, Poddighe D. Case series: efficacy and safety of hemoadsorption with HA-330 adsorber in septic pediatric patients with cancer. Front Pediatr 2021;9:672260.
62. Chu L, Li G, Yu Y, Bao X, Wei H, Hu M. Clinical effects of hemoperfusion combined with pulse high-volume hemofiltration on septic shock. Medicine (Baltimore) 2020;99e19058.
63. Monard C, Rimmelé T, Ronco C. Extracorporeal blood purification therapies for sepsis. Blood Purif 2019;47 Suppl 3:1–14.
64. Malard B, Lambert C, Kellum JA. In vitro comparison of the adsorption of inflammatory mediators by blood purification devices. Intensive Care Med Exp 2018;6:12.
65. Wei T, Chen Z, Li P, et al. Early use of endotoxin absorption by oXiris in abdominal septic shock: a case report. Medicine (Baltimore) 2020;99e19632.
66. Guan M, Wang H, Tang X, et al. Continuous renal replacement therapy with adsorbing filter oXiris in acute kidney injury with septic shock: a retrospective observational study. Front Med (Lausanne) 2022;9:789623.
67. Zhang L, Yan Tang GK, Liu S, et al. Hemofilter with adsorptive capacities: case report series. Blood Purif 2019;47 Suppl 3:1–6.
68. Fajgenbaum DC, June CH. Cytokine storm. N Engl J Med 2020;383:2255–2273.
69. Ronco C, Bagshaw SM, Bellomo R, et al. Extracorporeal blood purification and organ support in the critically ill patient during COVID-19 pandemic: expert review and recommendation. Blood Purif 2021;50:17–27.
70. Niazi NS, Nassar TI, Stewart IJ, Honore PM, Sharma K, Chung KK. A review of extracorporeal blood purification techniques for the treatment of critically ill coronavirus disease 2019 patients. ASAIO J 2022;68:1219–1227.
71. Rizvi S, Danic M, Silver M, LaBond V. Cytosorb filter: an adjunct for survival in the COVID-19 patient in cytokine storm? A case report. Heart Lung 2021;50:44–50.
72. Rampino T, Gregorini M, Perotti L, et al. Hemoperfusion with CytoSorb as adjuvant therapy in critically ill patients with SARS-CoV2 pneumonia. Blood Purif 2021;50:566–571.
73. Hashemian SM, Shafigh N, Afzal G, et al. Blood purification techniques, inflammatory mediators and mortality in COVID-19 patients. Tanaffos 2020;19:291–299.
74. Soleimani A, Taba SM, Hasibi Taheri S, Loghman AH, Shayestehpour M. The effect of hemoperfusion on the outcome, clinical and laboratory findings of patients with severe COVID-19: a retrospective study. New Microbes New Infect 2021;44:100937.
75. Berlot G, Tomasini A, Roman Pognuz E, et al. The combined use of tocilizumab and hemoadsorption in a patient with SARS-COV-2-19-associated pneumonia: a case report. Nephron 2020;144:459–462.
76. Rieder M, Wengenmayer T, Staudacher D, Duerschmied D, Supady A. Cytokine adsorption in patients with severe COVID-19 pneumonia requiring extracorporeal membrane oxygenation. Crit Care 2020;24:435.
77. Alharthy A, Faqihi F, Memish ZA, et al. Continuous renal replacement therapy with the addition of CytoSorb cartridge in critically ill patients with COVID-19 plus acute kidney injury: a case-series. Artif Organs 2021;45:E101–E112.
78. Stockmann H, Thelen P, Stroben F, et al. CytoSorb rescue for COVID-19 patients with vasoplegic shock and multiple organ failure: a prospective, open-label, randomized controlled pilot study. Crit Care Med 2022;50:964–976.
79. Kielstein JT, Borchina DN, Fühner T, Hwang S, Mattoon D, Ball AJ. Hemofiltration with the Seraph 100 Microbind Affinity Filter decreases SARS-CoV-2 nucleocapsid protein in critically ill COVID-19 patients. Crit Care 2021;25:190.
80. Olson SW, Oliver JD, Collen J, et al. Treatment for severe coronavirus disease 2019 with the Seraph-100 Microbind Affinity Blood Filter. Crit Care Explor 2020;2e0180.
81. Sandoval D, Rama I, Quero M, Hueso M, Gómez F, Cruzado JM. Treatment for severe COVID-19 with a biomimetic sorbent haemoperfusion device in patients on haemodialysis. Clin Kidney J 2021;14:1475–1477.
82. Schmidt JJ, Borchina DN, Van’t Klooster M, et al. Interim analysis of the COSA (COVID-19 patients treated with the Seraph 100 Microbind Affinity filter) registry. Nephrol Dial Transplant 2022;37:673–680.
83. Padala SA, Vakiti A, White JJ, Mulloy L, Mohammed A. First reported use of highly adsorptive hemofilter in critically ill COVID-19 patients in the USA. J Clin Med Res 2020;12:454–457.
84. Zhang H, Zhu G, Yan L, Lu Y, Fang Q, Shao F. The absorbing filter Oxiris in severe coronavirus disease 2019 patients: a case series. Artif Organs 2020;44:1296–1302.
85. Villa G, Romagnoli S, De Rosa S, et al. Blood purification therapy with a hemodiafilter featuring enhanced adsorptive properties for cytokine removal in patients presenting COVID-19: a pilot study. Crit Care 2020;24:605.
86. Faqihi F, Alharthy A, Alshaya R, et al. Reverse takotsubo cardiomyopathy in fulminant COVID-19 associated with cytokine release syndrome and resolution following therapeutic plasma exchange: a case-report. BMC Cardiovasc Disord 2020;20:389.
87. Botella J, Ghezzi PM, Sanz-Moreno C. Adsorption in hemodialysis. Kidney Int Suppl 2000;76:S60–S65.
88. Cheng W, Luo Y, Wang H, et al. Survival outcomes of hemoperfusion and hemodialysis versus hemodialysis in patients with end-stage renal disease: a systematic review and meta-analysis. Blood Purif 2022;51:213–225.
89. Chen SJ, Jiang GR, Shan JP, et al. Combination of maintenance hemodialysis with hemoperfusion: a safe and effective model of artificial kidney. Int J Artif Organs 2011;34:339–347.
90. Xiao Y. Effect of hemodialysis combined with blood perfusion on the treatment effect and long-term survival rate of patients with chronic renal failure and heart failure. J Med Ther Pract 2017;30:2725–2726.
91. Li X, Kong Y, Guanqing Xiao G, et al. Observation of medium and long term efficacy of hemodialysis combined with hemoperfusion on the endo-thelial function in patients with maintance hemodialysis. J Pract Med 2017;(24):3437–3440.
92. Zhong J, Huang Z, Li F. Effect of different dialysis methods on the outcome of patients with uremia complicated by heart failure and their effects on myocardial enzyme levels. J QDU Med 2018;054:407–409.
93. Wang Y, Wang Z, Ma S, Zhang H. Effect of hemoperfusion and hemodialysis on microinflammation and cardiovascular and cerebrovascular events in uremic patients. Chin J Heal C Med 2020;22:173–175.
94. Raine A, Cordonnier D, Ritz E. Effect of hematodialysis plus hemoperfusion on insulin resistance and nutritional status of patients with end-stage diabetic nephropathy. J Int Transl Med 2015;3:180–184.
95. Zhang J, Yuan Y, An X, et al. Comparison of combined blood purification techniques in treatment of dialysis patients with uraemic pruritus. Int J Clin Exp Med 2016;9:8563–8568.
96. Li WH, Yin YM, Chen H, et al. Curative effect of neutral macroporous resin hemoperfusion on treating hemodialysis patients with refractory uremic pruritus. Medicine (Baltimore) 2017;96e6160.
97. Long Q, Qin JP, Li R, Chang J, Jiang GR, Zhu C. Effects of hemodialysis and hemoperfusion combination treatment on maintenance hemodialysis patients. J Shanghai Jiaotong Univ (Med Sci) 2019;39:886–892.
98. He H, Xie Y. Effect of different hemodialysis methods on microbiota in uremic patients. Biomed Res Int 2020;2020:6739762.
99. Rocchetti MT, Cosola C, di Bari I, et al. Efficacy of divinylbenzenic resin in removing indoxyl sulfate and p-cresol sulfate in hemodialysis patients: results from an in vitro study and an in vivo pilot trial (xuanro4-Nature 3.2). Toxins (Basel) 2020;12:170.
100. Gu YH, Yang XH, Pan LH, Zhan XL, Guo LL, Jin HM. Additional hemoperfusion is associated with improved overall survival and self-reported sleep disturbance in patients on hemodialysis. Int J Artif Organs 2019;42:347–353.
101. Tang W, Sun X, Chen R, Zhao X. The observation effect of MHD combined with HP on improving the quality of life and prognosis of maintenance hemodialysis patients. Zhejiang Clin Med J 2014;12:1958–1959.
102. Yamaji K. Immunoadsorption for collagen and rheumatic diseases. Transfus Apher Sci 2017;56:666–670.
103. Stummvoll G, Aringer M, Handisurya A, Derfler K. Immunoadsorption in autoimmune diseases affecting the kidney. Semin Nephrol 2017;37:478–487.
104. Santos JM, Alolod MK. HA-130 hemoperfusion cartridge in the treatment of cast nephropathy in a 58-year-old male with multiple myeloma: a case report. Nephrol Dial Transplant 2020;35:iii1441.
105. Rosales A, Madrid A, Muñoz M, Dapena JL, Ariceta G. Charcoal hemoperfusion for methotrexate toxicity: a safe and effective life-rescue alternative when glucarpidase is not available. Front Pediatr 2021;9:635152.

Article information Continued

Figure 1.

Overview of hemoperfusion technique.

HD, hemodialysis; COVID-19, coronavirus disease 2019; ESRD, end-stage renal disease.

Figure 2.

Example of adsorption isotherm graph.

Adsorption increases steadily until it reaches equilibrium, which is when the concentration of the marker solute at the outlet of the unit is equal to the concentration at the inlet.

Ps, saturation pressure.

Figure 3.

Mechanism of solute adsorption in porous media.

Mechanisms of mass transport from the bulk solution to the sorbent surface. (A) External (interphase) mass transfer of the solute by convection from the bulk fluid by diffusion through a thin film of boundary layer to the outer surface of the sorbent. (B) Internal (intra-phase) mass transfer of the solute by pore convection from the outer surface of the adsorbent to the inner surface of the internal porous structure. (C) Surface diffusion along the porous surface and adsorption of the solute onto the porous surface. Reproduced from Clark et al. [16] with permission of Karger Publishers.

Table 1.

Summary of adsorbent types and their main advantages, disadvantages, and clinical indications

Adsorbent type Advantage Disadvantage Example Clinical availability Clinical indication
Activated carbon (natural or resin-based) [811,15] Low cost, high adsorption capacity Poor biocompatibility Adsorba (coated with cellulose acetate) Intoxication
Stable under physiological conditions Lack of selective adsorption
Inorganic porous material (e.g., mesoporous silica, silica gel) [1215] Reusability, pore size highly variable for different sizes of toxin molecules High cost, variable results in biocompatibility, poor modifiability, limited structural design possibility LiChroprep RP-18 Removal of bilirubin and uric acid, medicine removal
Natural (e.g., polysaccharide) or synthetic polymeric materials [15] Hemocompatibility, high stability, bioinertia, structure designability and modifiability, low cost Selectivity of natural polymeric materials not advantageous CytoSorb, HA 330, Toraymyxin + Wide range

Data reproduced from references.

Table 2.

List of drugs and the recommended extracorporeal therapy in case of acute poisoning

Drug The first choice of extracorporeal modality Acceptable alternatives
Acetaminophen Intermittent HD (1D) Intermittent HP (1D), CRRT (3D)
Baclofen Not recommended (1D)
Barbiturates Intermittent HD (1D) HP (1D) or CRRT (3D)
B-blockers
Propranolol Not recommended (1D)
Atenolol Intermittent HD (1D) only in severe poisoning with kidney impairment
Sotalol
Calcium channel blockers Not recommended (1D)
Carbamazepine Intermittent HD (1D) Intermittent HP (1D), CRRT (3D)
Digoxin Not recommended (1D)
Gabapentin/pregabalin Intermittent HD (1D) only in severe poisoning with kidney impairment
Isoniazid Not recommended (2D), consider extracorporeal therapy where pyridoxine cannot be administrated (2D)
Lithium Intermittent HD (1D) CRRT (1D)
Metformin Intermittent HD (1D) CRRT (2D)
Methanol Intermittent HD (1D) CRRT (1D)
Methotrexate Not recommended (2D) when glucarpidase is not administrated, not recommended (1D) when glucarpidase is administrated, not recommended (1D) instead of administrating glucarpidase
Phenytoin Intermittent HD (1D) Intermittent HP (1D)
Quinine/chloroquine Not recommended (1D)
Salicylates Intermittent HD (1D) Intermittent HP (1D), CRRT (3D)
Thallium Intermittent HD (1D) Intermittent HP (1D), CRRT (1D)
Theophylline Intermittent HD (1C) Intermittent HP (1C), CRRT (3D)
Tricyclic antidepressants Not recommended (1D)
Valproic acid Intermittent HD (1D) Intermittent HP (1D), CRRT (2D)

CRRT, continuous renal-replacement therapies; HD, hemodialysis; HP, hemoperfusion.

Table 3.

Summary of characteristics and main results of the most frequently used HP filters in the field of sepsis and COVID-19 infection

Filter Selectivity Targets Indications Combined treatment Results
Toraymyxin (Today Industries Ltd.) [4952,69] + Endotoxins, inflammatory mediators, cytokines Sepsis with positive culture for Gram-negative bacteria/high endotoxin activity assay level, severe sepsis or septic shock from an abdominal cause, COVID-19 infection with septic shock Higher hemodynamic and ventilation parameters
Unclear results for mortality
CytoSorb (CytoSorbents corporation) [5358,6978] - Inflammatory mediators, cytokines, albumin-bound substances and pathogenic toxins but not effective removal of endotoxin Severe sepsis or septic shock (cytokine storm) and ARDS, COVID-19 infectiona HD SCUF CRRT ECMO Higher hemodynamic parameters and improved respiratory distress
Unclear results for mortality and for reduction of IL-6
HA series (Jafron Biomedical Company) [5962,69] - Inflammatory mediators, cytokines, complement, free hemoglobin and myoglobin Severe sepsis or septic shock +/– acute lung injury, COVID-19 infection CRRT ECMO Reduction of inflammatory cytokine levels and improved hemodynamic parameters
Unclear results for mortality
oXiris (Baxter Inc.) [6468,70,8385] - Endotoxins, inflammatory mediators and cytokines with potential antithrombogenic properties COVID-19 infectiona, sepsis with AKI Stand-alone filter for SCUF and CRRT Reduction in inflammatory markers and improved hemodynamics
Limited experience on mortality
Seraph 100 Microbind Blood Affinity Filter (ExThera Medical Corporation) [70,7982] - Pathogens and proinflammatory cytokines COVID-19a HD CRRT Improvement in circulatory dysfunction and in inflammatory markers (CRP and IL-6), initial results showing lower mortality
Spectra Optia Apheresis and Depuro D2000 Adsorption Cartridge (Terumo BCT) [70,86] - Endotoxins, inflammatory mediators and cytokines COVID-19a Therapeutic apheresis Limited experience

Data reproduced from references.

AKI, acute kidney injury; ARDS, acute respiratory distress syndrome; COVID-19, coronavirus disease 2019; CRP, C-reactive protein; CRRT, continuous renal-replacement therapy; ECMO, extracorporeal membrane oxygenation; HD, hemodialysis; IL, interleukin; SCUF, slow-continuous ultrafiltration.

a

Devices approved by U.S. Food and Drug Administration for the treatment of severe COVID-19 infection.