Chemical-Physical Mechanisms of Adsorption for Blood Purification

Blood purification is indispensable in addressing various conditions such as liver dysfunction, autoimmune diseases, and renal failure whereby toxins have to be cleared from the bloodstream effectively. Conventional methods that involve hemoperfusion, hemodialysis, and hemofiltration possess several weaknesses, including loss of plasma components and inefficient clearance of high molecular weight solutes. This review explores current developments in blood purification techniques particularly stimuli-responsive polymers for use in extracorporeal therapy among other applications. Many aspects of engineering stimuli-responsive polymers are described in terms of their role in the removal of small soluble molecules and toxins in blood purification techniques. The development of stimuli-responsive systems has introduced a new paradigm in blood purification by enabling selective, on-demand control of polymer parameters in response to external stimuli such as temperature, pH, electrolytes, and light. Such advanced materials have been demonstrated potential for toxin clearance, minimizing thrombosis, and improving blood compatibility and antifouling, which are far much better than traditional approaches. Furthermore, the review presents a perspective on stimuli-responsive polymers that could be used in developing novel extracorporeal systems for future medical purposes.

Chronic kidney disease (CKD) is a highly prevalent condition that is associated with an increased burden of cardiovascular diseases and mortality. Between 7% and 12% of the general population are affected by CKD. In patients with end-stage renal disease (ESRD), the most severe form of CKD, large amounts of uremic toxins are retained in the blood due to impaired kidney function, leading to uremic symptoms and functional as well as biochemical alterations. Currently, extracorporeal blood purification techniques, including hemodialysis, hemofiltration, hemodiafiltration, and hemoperfusion, are widely used to remove small- to medium-sized uremic toxins, maintain homeostasis, and sustain the lives of ESRD patients. However, the available blood purification methods do not efficiently eliminate protein-bound uremic toxins (PBUTs), such as indoxyl sulfate (IS), hippuric acid (HA), p-cresyl sulfate (PCS), and indole-3-acetate (IAA), due to their strong affinity for albumin. The accumulation of PBUTs unfortunately contributes to kidney fibrosis, oxidative stress, cardiovascular events, and poor long-term survival. Therefore, the development of novel blood purification techniques to improve PBUT elimination is of considerable clinical significance. In this review, we first discuss the limitations of current blood purification modalities of PBUT removal and then summarize recent advances in hemoperfusion adsorbents, adsorptive hemodialysis membranes, and dialysate regeneration systems with enhanced PBUT clearance. Finally, we discuss potential challenges and future research directions in this field, with the aim of providing opportunities for more personalized and targeted blood purification therapies for ESRD patients.

Objective To investigate the effect of three blood purification techniques on minerals disorder in maintenance hemodialysis patients,and provide clinical guidance for patients to choice the blood purification techniques.Methods Eighty-eight maintenance hemodialysis patients were divided into three groups according to the blood purification techniques:hemodialysis (HD) group (30 cases),hemodiafiltration (HDF) group (30 cases),and hemoperfusion (HP) group (28 cases).Serum urea nitrogen,creatinine,calcium,phosphorus,intact parathyroid hormone (iPTH),ftbroblast growth factor (FGF)-23 and so on before and after treatment were measured and compared among the groups.Results The serum phosphorus in HD group,HDF group and HP group before treatment were (1.93 ±0.44),(2.11 ±0.54) and (2.17 ±0.59)mmol/L,and after treatment were (1.01 ±0.23),(0.84 ±0.19),(0.99 ±0.27) mmol/L.There were significant differences in serum phosphorus level after treatment compared with that before treatment in the three groups (P ＜0.05).There were no significant differences in the descend rate of serum phosphorus among the three groups (P ＞0.05).There were no significant differences in clearance index of serum phosphorus among the three groups (P ＞ 0.05).The serum iPTH in HD group before treatment was (48.8 ± 42.9) pmol/L,and after treatment was (49.9 ± 42.9) pmol/L.The serum iPTH in HDF group and HP group before treatment were (64.7 ± 45.4) and (50.4 ± 45.9) pmol/L,after treatment was (46.2 ± 37.8) and (35.8 ± 36.5) pmol/L.There were significant differences in serum iPTH level after treatment compared with that before treatment (P ＜ 0.05).There were no significant differences in the descend rate and clearance index of serum iPTH in HDF group and HP group (P ＞ 0.05).There was no significant difference in serum FGF-23 in HD group before and after treatment (P＞ 0.05).The serum FGF-23 in HDF group and HP group before treatment were (782.5 ± 105.8) and (879.5 ±97.2) ng/L,after treatment were (712.0 ±98.1),(823.5 ± 89.1) ng/L.There were significant differences in serum iPTH level after treatment compared with that before treatment in HDF group and HP group (P ＜ 0.05).The descend rate of serum FGF-23 in HD group,HDF group and HP group were (5.7 ±2.8)％,(12.3 ±6.2)％ and (9.1 ±4.6)％,and there was significant difference among the three groups (P ＜0.05).The clearance index of serum FGF-23 in HD group,HD F group and HP group were 0.06 ± 0.05,0.19 ± 0.11 and 0.12 ± 0.08,and there were significant differences among the three groups (P ＜ 0.05).There were no significant differences in the descend rate and clearance index of serum urea among the three groups (P ＞ 0.05).Conclusions HD can only clear serum phosphorus.HDF and HP can clear serum phosphorus,iPTH and FGF-23 effectively,while HDF has better clearance effect on FGF-23.The HDF and HP blood purification can reduce minerals disorder in maintenance hemodialysis patients and has important clinical significance in improving the long-term prognosis of the patients. Key words: Calcium; Phosphorus; Renal dialysis; Hemodiafiltration; Hemoperfusion

The prognosis of patients with an acute accumulation of pathogenic or toxic substances in their body fluids--a condition that severely affects survival--can be significantly improved by blood purification. The most appropriate blood purification method and the duration for which it should be used must be selected on the basis of efficacy and cost. Several blood purification techniques--such as hemodialysis (HD), hemofiltration (HF), hemodiafiltration, continuous hemofiltration (CHF), hemadsorption and plasma exchange--have been developed. Each modality has different removal capacities and limitations; therefore, it is necessary to thoroughly evaluate the time and the duration of use in the case of different disease conditions. The survival rate of patients treated with HF with 35 ml/min of average filtrate is higher than that observed after conventional HD. In patients with systemic inflammatory response syndrome and multiple organ dysfunction syndrome, proinflammatory cytokines should be removed by HF or CHF, as should the toxins accumulated in the original disease. Thus far, no ideal filter has been developed for the removal of a considerable amount of proinflammatory cytokines with minimal albumin loss. In the case of acute liver failure, ammonia, amino acid metabolites and albumin-binding bilirubin should be removed by a combination of HF and plasma exchange. The use of fresh frozen plasma as a replacement fluid in plasma exchange is also important in order to replenish the deficient coagulation factors and essential metabolic factors. Activation of tissue/organ regeneration by the removal of pathogenic factors or by the substitution of factors essential for regeneration might be important in the case of multiple organ dysfunction syndrome. In critically ill patients with composite conditions, the use of more than two blood purification techniques at the same time or at different times during the course of the diseases can improve patient prognosis more than the use of single methods.

Data on clinical applications of blood purification techniques in children are scarce. The aim of this review is to offer a clinical overview, as complete as possible, on blood purification in children with hyper-inflammatory syndromes (HS). A review of the literature using the PubMed, EMBASE, Web of Science, and Scopus databases, on the most recent data about blood purification in children was conducted until June 2018. Except for three randomized controlled trials (RCTs) on plasma exchange, no RCTs, but only observational studies or case reports were found regarding other blood purification techniques in children. High-volume hemofiltration in two non-randomized trials did not significantly reduce 28-day mortality in children. PE was not associated with reduced mortality in pediatric patients with septic shock, but the small number of patients enrolled is an important limitation. The use of polymixin B and other adsorbing columns in children with septic shock and HS is increasing, but results are still limited by the observational nature of the studies. Based on the low-level of available evidence, no conclusions can be drawn regarding the efficacy and safety of blood purification in children. Further research with more clinically robust data is needed to determine the impact of different extracorporeal blood purification techniques in this pediatric population.

The use of semipermeable membranes for multicomponent separations based on molecular size has long been recognized. In certain applications, however, it is often desirable not to effect a separation of chemical constituents, but to sustain a separation which already exists. As an example, the efficient and economical design of a. chemical reactor using an enzyme as a catalyst depends on the accessibility of the reactant to the catalyst as well as on the degree to which a physical separation between the enzyme and the reactor product stream is maintained. A particularly simple and attractive means of achieving this is through the use of semipermeable asymmetric hollow fiber membranes. For example, by sequestering an enzyme solution within the annular macroporous support regions of an asymmetric hollow fiber, a physical separation between enzyme and a reactant solution flowing through the fiber lumen is achieved. In this way, small reactant molecules are free to diffuse across the ultrathin membran...

Although blood purification improves outcomes in animal studies of sepsis, results of clinical trials have been mixed. We conducted a systematic review and meta-analysis of randomized trials to determine the association between various blood purification techniques and all-cause mortality in humans with sepsis. We searched for relevant studies in MEDLINE, EMBASE, and the Cochrane Library database from January 1966 to May 2012. Inclusion required a diagnosis of sepsis and comparison of blood purification techniques including hemofiltration, hemoperfusion, plasma exchange, or hemodialysis with no blood purification (control group). Two authors independently selected studies and extracted data. Summary statistics, risk ratios, and CIs were calculated using random-effects modeling. Study quality was assessed using Jadad score, and publication bias was assessed using funnel plots and Egger's statistic. Overall, blood purification decreased mortality compared with no blood purification (35.7% vs 50.1%; risk ratio, 0.69 [95% CI, 0.56-0.84]; p<0.001; 16 trials, n=827). However, these results were driven mainly by hemoperfusion (risk ratio, 0.63 [95% CI, 0.50-0.80]; p<0.001; 10 trials, n=557) and plasma exchange (risk ratio, 0.63 [95% CI, 0.42-0.96]; p=0.03; two trials, n=128). Pooling of all trials of blood purification for treatment of sepsis was no longer associated with lower mortality (risk ratio, 0.89 [95% CI, 0.71-1.13]; p=0.36; eight trials, n=457) after excluding trials using polymyxin B hemoperfusion. Blood purification techniques including hemoperfusion, plasma exchange, and hemofiltration with hemoperfusion were associated with lower mortality in patients with sepsis. These results were mainly influenced by studies using polymyxin B hemoperfusion from Japan.

Objective To compare different blood purification techniques on serum fibroblast growth factor 23(FGF-23) scavenging effect in patients undergoing maintenance hemodialysis (MHD), in order to choose the best blood purification method for clinical maintenance hemodialysis patients. Methods 60 MHD patients were randomly divided into hemodialysis group (HD), hemodiafiltration group (HDF) and HD+ HP group, 20 cases in each group.Three groups of patients in the observation 1st start of treatment and observation at the end of the last treatment were detected cacium, phosphorus, FGF-23, intact parathyroid hormone(iPTH). Results After treatment, HD group and HDF group, Ca: t=0.29, P=0.77; P: t=1.65, P=0.11; iPTH: t=16.85, P=0.00; HD group and HD+ HP group: Ca: t=0.20, P=0.84; P: t=2.62, P=0.01; iPTH: t=42.64, P=0.00; HDF group and HD+ HP group: Ca: t=0.09, P=0.92; P: t=2.18, P=0.04; iPTH: t=31.41, P=0.00.After treatment, FGF-23 in the three groups were decreased significantly than before treatment, and the HD+ HP group decreased most significantly(HD group and HDF group, t=4.47, P=0.00; HD group and HD+ HP group: t=8.06, P=0.00; HDF group and HD+ HP group: t=3.20, P=0.00). Conclusion HD+ HP treatment can effectively remove phosphorus maintenance dialysis patients and FGF-23. Key words: Maintenance dialysis; Fibroblast growth factor-23; Blood purification

Objectives To analyse the efficacy of different blood purification techniques on chronic renal failure(CRF).Methods Totally 65 CRF patients who need to be given blood purification treatment in our hospital from 2005 to 2011 were selected and randomly divided into three group,including 24cases in hemodialysis and hemoperfusion(HD + HP) group,21cases in hemodialysis(HD) group and 20cases in peritoneal dialysis(PD) group.Compare the change of clinical indicators after the treatment of blood purification.Results Compared with the clinical indicators including BUN,Cr,SBP,DBP,Hb and CO2 CP of each group before and after treatment,there were significant differences(P ＜ 0.05).Moreover,there was significant difference in β2-MG after treatment in HD + HP group(P ＜0.05) while there were no significant difference in β2-MG after treatment in HD group and PD group(P ＞ 0.05).Conclusions HD + HP,HD and PD these three blood purification treatment can effectively improve the clinical indicators of CRF patients,including BUN,Cr,SBP,DBP,Hb and CO2CP.Moreover,HD + HP has a more significant effect on clearing β2-MG. Key words: Kidney Failure, Chronic; Decontamination

Objective To compare different blood purification techniques on cardiovascular stability in patients with chronic renal failure (CRF) and its inherent possible mechanism. Methods 90patients with CRF were randomly divided into 3 groups. Group A (HD Group) was applied 3 times per week hemodialysis (HD) treatment; Group B (HDF group) 2 times a week routine standard hemodialysis (HD)treatment and 1 time a week hemodiafiltration (HDF) treatment; Group C (HP group) 2 times a week routine standard blood dialysis (HD) treatment and 1 time a week hemoperfusion (HP) combined with hemodialysis (HD) treatment. The treatment time in every group is 10 weeks, after that there was an interval of 2 weeks with a Fresenius F6 or F8 routine HD treatment , the total time was 6 months. The incidence of cardiovascular complications in the three groups during dialysis, and parathyroid hormone (iPTH), plasma renin (RA),angiotensin Ⅱ (Ang Ⅱ ) changes after 6 months of treatment were compared. Results During dialysis,patients of groups B and C compared with group A significantly reduced cardiovascular complications( group B is 11.3%, group C is 10.9%, but group A is 20.4% ), after treatment plasma iPTH, renin (RA),angiotensin Ⅱ (Ang Ⅱ ) were also decreased significantly compared with group A, but the groups B and C had no significant difference. Conclusion Patients with Hemodialysis or hemoperfusion treatment have better cardiovascular stability, This may be associated with the effective removal of plasma RA, Ang Ⅱ , parathyroid hormone (iPTH) and other middle molecule toxins, both treatments have an equal effect due to simple operation and low equipment requirements, hemoperfusion is much easier to be carried out universally. Key words: Cardiovascular complications; Hemodiafiltration HDF; Hemoperfusion; Parathyroid hormone; Renin; Angiotensin Ⅱ (Ang Ⅱ )

Therapeutic Plasma Exchange: Core Curriculum 2008

Even in the absence of strong indications deriving from clinical studies, the removal of mediators is increasingly used in septic shock and in other clinical conditions characterized by a hyperinflammatory response. Despite the different underlying mechanisms of action, they are collectively indicated as blood purification techniques. Their main categories include blood- and plasma processing procedures, which can run in a stand-alone mode or, more commonly, in association with a renal replacement treatment. The different techniques and principles of function, the clinical evidence derived from multiple clinical investigations, and the possible side effects are reviewed and discussed along with the persisting uncertainties about their precise role in the therapeutic armamentarium of these syndromes.

Sepsis is the second leading cause of death in the intensive care unit (ICU) after coronary heart disease. Blood purification (BP) technology is a protocol for treating sepsis patients, but efficacy is controversial. Herein, we did a meta-analysis of the last 5 years of studies to investigate the clinical efficacy of blood purification in the treatment of sepsis. We searched for studies of BP treatment of sepsis patients on PubMed, Embase, Medline, and Cochrane library. Two independent reviewers assessed included studies and met to develop consensus on included studies. We also used Review Manager 5.3 software to evaluate the risk of bias. The present meta-analysis included 13 randomized controlled trials (RCT) containing 1,230 sepsis patients. In the fixed-effect meta-analysis of 13 RCTs, BP treatment had a statistically significant efficacy on mortality (OR = 0.76, 95% CI = 0.6 - 0.97, p = 0.03) and ICU stay time (SMD = -3.42, 95% CI = -5.30 to -1.54, p < 0.001) reduction for patients with sepsis. Further subgroup analysis showed that none of high-volume hemofiltration (OR = 0.69, 95% CI = 0.42 - 1.12, p = 0.13), polymyxin B blood perfusion (OR = 0.92, 95% CI = 0.64 - 1.30, p = 0.62), and cytokine adsorption (OR = 0.66, 95% CI = 0.37 - 1.17, p = 0.15) significantly reduced mortality in sepsis patients. Adjuvant blood purification therapy can reduce mortality and shorten ICU stay for patients with sepsis, but the clinical efficacy of different blood purification techniques is inconsistent.

Even today, little is known about the pathophysiology of the post-resuscitation syndrome. Our narrative review is one of the first summarizing all the knowledge about this phenomenon. We have focused our review upon the potential role of blood purification in attenuating the consequences of the post-resuscitation syndrome. Blood purification can decrease the cytokine storm particularly when using a CytoSorb absorber. Acrylonitrile 69-based oXiris membranes can remove endotoxin and high-mobility group box 1 protein. Blood purification techniques can quickly induce hypothermia. Blood purification can be used with veno-arterial extracorporeal membrane oxygenation to remove excess water. Further trials are needed to provide more concrete data about the use of blood purification in the post-resuscitation syndrome.

To observe the effect of sub-hypothermia (HT) blood purification technique in the treatment of cardiac shock after heart valve disease.The patients were randomly divided into normothermic (NT) continuous blood purification (CBP) group (NT group) and HT CBP group (HT group). Observe the cardiac index (CI), the oxygen delivery (DO2) and oxygen consumption (VO2) ratio, Acute Physiology and Chronic Health Evaluation III(APACHE III) score, multiple organ dysfunction syndrome (MODS) score, dynamic monitoring of electrocardiograph, blood loss with or without muscle tremors, intensive care unit stay, mechanical ventilation time, CBP time, and the cases of infection and mortality at 0 day, 1 day, 2 day, 3 day; all above indicators were compared between 2 groups.Ninety-five patients were randomly assigned into HT group (48 cases) and NT group (47 cases); there were no significant differences between the 2 groups for age, gender, pre-operative cardiac function, cardiothoracic ratio, and type of valve replacement (P > .05). There were no significant differences among the 1 day, 2 day, 3 day after recruited for CI, DO2/VO2 ratio, APACHE III score, MODS score (P > .05). But in HT group, DO2/VO2 ratio had been significantly improved after treatment for 1 day (2.5 ± 0.7 vs 1.8 ± 0.4, P = .024), and CI (3.0 ± 0.5 vs 1.9 ± 0.7, P = .004), APACHE III score (50.6 ± 6.2 vs 77.5 ± 5.5 P = .022), MODS score (6.0 ± 1.5 vs 9.3 ± 3.4, P = .013) also had been significantly improved after treatment for 3 days. In clinical outcomes, there were no significant differences between 2 groups for blood loss (617.0 ± 60.7 ml vs 550.9 ± 85.2 ml, P = .203), infection ratio (54.17% vs 53.19%, P = .341), the incidence of ventricular arrhythmia (31.25% vs 36.17%, P = .237), and muscle tremors (14.58% vs 8.51%, P = .346), while there were significant differences between 2 groups for intensive care unit stay (6.9 ± 3.4 days vs 12.5 ± 3.5 days, P = .017,), mechanical ventilation time (4.2 ± 1.3 days vs 7.5 ± 2.7 days, P = .034,), CBP time (4.6 ± 1.4 days vs 10.5 ± 4.0 days, P = .019), mortality (12.50% vs 23.40%, P = .024). But the incidence of bradycardia in HT group was much higher than the NT group (29.16% vs 14.89%, P = .029).HT blood purification is a safer and more effective treatment than NT blood purification for patients who suffered from cardiac shock after valve surgery.