Blood Purification Techniques Research Articles

Therapeutic Plasma Exchange Using Membrane Plasma Separation.

Therapeutic plasma exchange is a blood purification technique designed for the removal of large molecular weight toxins such as pathogenic antibodies and lipoproteins. Plasma exchange can be performed either by membrane separation or centrifugation. Centrifugal plasma exchange is more common in the United States, while membrane separation is more popular in Germany and Japan. The membrane separation technique is similar to the ultrafiltration procedures performed with a standard dialysis machine but in which the membrane's pores are large enough to allow removal of all circulating molecules while retaining the cellular components. The current availability of plasma separation membranes compatible with CRRT systems has dramatically increased the potential for almost all nephrologists to perform these treatments. This review describes the membrane separation techniques available in the United States, the practical aspects of ordering and operating a membrane separation plasma exchange procedure, and its possible complications.

Immunoadsorption for Treatment of Antibody Mediated Rejection after Lung Transplantation

Antibody mediated rejection (AMR) has recently emerged as an important risk factor for lung allograft dysfunction and mortality. Several clinical protocols have been proposed to try to remove donor specific antibodies (DSA) and prevent their future development, including intravenous immunoglobulin (IVIG), therapeutic plasma exchange (TPE), rituximab and other. Unlike traditional TPE, immunoadsorption (IAS) is a blood-purification technique that enables the selective removal of immunoglobulins from separated plasma through high-affinity adsorbers; advantageously, IAS does not remove other plasma components such as fibrinogen and compounds of the coagulation cascade, reducing potential adverse effects. Our centre implemented a multimodality strategy including steroids, immunoadsorbption, IVIG and Rituximab. All adult lung transplant (LuTx) recipients receiving a diagnosis of AMR (based on 2016 ISHLT consensus definition), were considered eligible to receive this treatment: pulsed methylprednisolone (10 mg/Kg), 5 cycles of IAS, IVIG (2 g/Kg) and rituximab (375 mg/m^2). Of note, C4d staining is not currently available at our institution. Between 2016 and 2018, four patients received multimodality antibody directed therapy for AMR after LuTx. Details can be found in table 1. 2 out of the 4 patients qualified for chronic lung allograft dysfunction (CLAD) prior to protocol start (patient 1 and 3). No adverse events were registered during IAS procedures, but patient 3 suffered transfusion related acute lung injury while receiving IVIG. However, patient 3's death was attributed to progressive allograft failure and not to the therapy itself. Following this treatment, while the total number of the original DSA and the value of MFI of the originally observed DSA decreased, clinical outcomes were variable: 2 patients are experiencing long term clinical stability, but the others rapidly progressed to severe CLAD.

Effect of sub-hypothermia blood purification technique in cardiac shock after valvular disease surgery.

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.

Coronavirus epidemic: preparing for extracorporeal organ support in intensive care

Coronavirus epidemic: preparing for extracorporeal organ support in intensive care

COVID-19 Pandemic Causing Acute Kidney Injury and Impact on Patients With Chronic Kidney Disease and Renal Transplantation.

Coronavirus disease 2019 (COVID-19) caused by 2019 novel coronavirus (2019-nCoV) has caused significant mortality and has been declared as a global pandemic by the World Health Organization. The infection mainly presents as fever, cough, and breathing difficulty, and few patients develop very severe symptoms. The purpose of this review is to analyze the impact of the virus on the kidney. COVID-19 infection causes acute kidney injury (AKI) and is an independent risk factor for mortality. Angiotensin-converting enzyme 2 (ACE2) receptors, direct viral damage, and immune-mediated damage play important roles in the pathogenesis. AKI in COVID-19 infection could be from the synergistic effect of virus-induced direct cytotropic effect and cytokine-induced systemic inflammatory response. AKI caused in the viral infection has been analyzed from the available epidemiological studies. The proportion of patients developing AKI is significantly higher when they develop severe disease. Continuous renal replacement therapy (CRRT) is the most used blood purification technique when needed. The impact of COVID-19 infection on chronic kidney disease (CKD) and renal transplant patients is also discussed in the manuscript. No vaccine has been developed against the 2019-nCoV virus to date. The critical aspect of management is supportive care. Several investigative drugs have been studied, drugs approved for other indications have been used, and several clinical trials are underway across the globe. Recently remdesivir has received emergency use authorization by the Food and Drug Administration (FDA) in the USA for use in patients hospitalized with COVID-19. Prevention of the infection holds the key to management. The patients with underlying kidney problems and renal transplant patients are vulnerable to developing COVID-19 infection.

Control of Hypercytokinemia in Critically Ill Epstein-Barr Virus Related Hemophagocytic Lymphohistiocytosis with Plasma Exchange and Continuous Renal Replacement Therapy

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a severe and potentially fatal disease associated with abnormal function of the immune system. Epstein-Barr virus (EBV) is one of the most common triggers of HLH, especially in Asian countries. The control of EBV-HLH is still a challenging issue, particularly the early mortality, which was mainly due to the multi-organ failure coursed by hypercytokinemia. Therefore, control the hypercytokinemia induced by EBV are very important in critical ill EBV-HLH patients. Extracorporeal blood purification techniques already have been successfully applied to control hypercytokinemia in sepsis and septic shock patients. But there are few studies by using plasma exchange (PE) and continuous renal replacement therapy (CRRT) to treat critically ill EBV-HLH. This study aimed to evaluate the effect of PE+CRRT in the control of hypercytokinemia in critical ill EBV-HLH patients. Material and methods: The diagnosis a series of critically ill EBV-HLH patients admitted to the pediatric intensive care unit (PICU) were confirmed by comparing to the clinical and laboratory criteria of the HLH-2004 consensus. Real time polymerase chain reaction was used to detect EBV-DNA copies in the patients' serum, all the patients showed a significantly increasing of EBV-DNA copies in the serum (>1×104 Copies/mL). With the approval of the Ethics Committee and informed consents from the guardians of the patients, PE and CRRT combined HLH-2004 chemo-immunotherapy was used to treat these cases at the initial treatment, all the PE and CRRT sessions were finished in 3-7 days according to the condition of the patients. In addition, other supportive treatments were applied accordingly. The levels of cytokines were measured by using the CBA Human Th1/Th2 Cytokine Kit II (BD Biosciences, San Jose, California). Death occurred in 30 days after the initiation of treatment was defined as early death. Results: Clinical symptoms of all patients were remarkably improved after the PE and CRRT sessions. The EBV-DNA copies in the patients' serum was significantly decreased to around the limits of detection. And the abnormal high levels of cytokines were rapidly recovered to normal values. More importantly, no serious side effects were observed during the treatment. In addition, all the patients except one patient who did not continue the therapy achieved complete remission after 4 weeks' treatment, and no early death occurred in 30 days after the initiation of the treatment. Furthermore, the EBV-DNA were undetectable in the serum of these patients after 6 months. The remissions of these patients were maintained for a median time of 17 months (13-22 months). Conclusions: PE+CRRT associated HLH-2004 chemo-immunotherapy is a safe and effective strategy to control hypercytokinemia in critically ill EBV-HLH patients, and may help in the reduction of early death. More data from randomized, large-scale and multicenter studies are needed to make this conclusion more reliable. Disclosures No relevant conflicts of interest to declare.

Análisis del uso y complicaciones del acceso vascular periférico en la técnica del recambio plasmático terapéutico mediante centrifugación

Introducción: El recambio plasmático terapéutico es una técnica extracorpórea de depuración sanguínea. El recambio plasmático terapéutico mediante el método de centrifugación (plasmacentrifugación) requiere flujos de 50 ml/min lo que permite realizar el intercambio con accesos vasculares periféricos. El principal objetivo de este estudio fué el de analizar el uso y las complicaciones del acceso vascular periférico en las sesiones de plasmacentrifugación. Material y Método: Estudio observacional descriptivo longitudinal sobre el análisis de complicaciones del acceso vascular periférico de las sesiones de plasmacentrifugación realizadas entre enero de 2017 y marzo de 2018. Resultados: Inclusión de un total de 93 sesiones de plasmacentrifugación, estas sesiones fueron llevadas a cabo en 9 pacientes con una mediana de 7 [P25:6; P75:10,5] sesiones por paciente. El 66,66% (n=6) fueron mujeres. En el 89,24% (n=83) de las sesiones se usó la centrifugación y en el 10,75% (n=10) la fotoaféresis. La etiología de enfermedad para estos pacientes fue: renal en el 55,55% (n=5) de los casos, neurológica en el 33,33% (n=3) de los casos y dermatológica en el 11,11% (n=1). De las 93 sesiones totales hubo problemas relacionados con la canalización de un acceso vascular periférico en el 52,69% de las sesiones (n=49). Conclusiones: Debido a que en más de la mitad de las sesiones se presentaron complicaciones en el abordaje del acceso vascular periférico, se concluye que es necesario el estudio vascular ambulatorio del paciente antes de la primera sesión, pudiendo ser útil el uso de la punción ecoguiada.

Blood Purification and Mortality in Sepsis and Septic Shock: A Systematic Review and Meta-analysis of Randomized Trials.

Sepsis and septic shock are severe inflammatory conditions related to high morbidity and mortality. We performed a systematic review with meta-analysis of randomized trials to assess whether extracorporeal blood purification reduces mortality in this setting. Electronic databases were searched for pertinent studies up to January 2019. We included randomized controlled trials on the use of hemoperfusion, hemofiltration without a renal replacement purpose, and plasmapheresis as a blood purification technique in comparison to conventional therapy in adult patients with sepsis and septic shock. The primary outcome was mortality at the longest follow-up available. We calculated relative risks and 95% CIs. The grading of recommendations assessment, development and evaluation methodology for the certainty of evidence was used. Thirty-seven trials with 2,499 patients were included in the meta-analysis. Hemoperfusion was associated with lower mortality compared to conventional therapy (relative risk = 0.88 [95% CI, 0.78 to 0.98], P = 0.02, very low certainty evidence). Low risk of bias trials on polymyxin B immobilized filter hemoperfusion showed no mortality difference versus control (relative risk = 1.14 [95% CI, 0.96 to 1.36], P = 0.12, moderate certainty evidence), while recent trials found an increased mortality (relative risk = 1.22 [95% CI, 1.03 to 1.45], P = 0.02, low certainty evidence); trials performed in the United States and Europe had no significant difference in mortality (relative risk = 1.13 [95% CI, 0.96 to 1.34], P = 0.15), while trials performed in Asia had a positive treatment effect (relative risk = 0.57 [95% CI, 0.47 to 0.69], P < 0.001). Hemofiltration (relative risk = 0.79 [95% CI, 0.63 to 1.00], P = 0.05, very low certainty evidence) and plasmapheresis (relative risk = 0.63 [95% CI, 0.42 to 0.96], P = 0.03, very low certainty evidence) were associated with a lower mortality. Very low-quality randomized evidence demonstrates that the use of hemoperfusion, hemofiltration, or plasmapheresis may reduce mortality in sepsis or septic shock. Existing evidence of moderate quality and certainty does not provide any support for a difference in mortality using polymyxin B hemoperfusion. Further high-quality randomized trials are needed before systematic implementation of these therapies in clinical practice.

IMMUNOMODULATION, IMMUNOSTIMULATION AND EXTRACORPOREAL BLOOD PURIFICATION IN SEPSIS: POTENTIALLY BENEFICIAL TECHNIQUES IN CARDIAC SURGERY

Sepsis is a potentially life-threatening state caused by an infection and an inadequate, dysregulated host immune response. Focusing on cardiac surgery, the prevalence of sepsis is low, after procedures situated between 0.39% and 2.5%. Nevertheless, the current life-expectancy of septic patients are poor, mortality varying from 65% to 79%.Pathophysiology and immunopathology of sepsis is still unclear. Actually we consider sepsis as a dynamic process with two different sides. Both immune hyperactivity and immune suppression are presented during the progression. Although immunomodulation is not a fresh idea in the treatment of sepsis. Currently the diagnosis of sepsis is based on clinical signs. The biomarkers and molecular diagnostic tools are insufficient.The actual concept of immunopathophysiology in sepsis is based on the idea of a dynamic parallel immune response, both pro- and antiinflammatory processes are presented from the beginning. Equilibrium may be the key in the immune response of sepsis. Immune system tries to maintain the homeostatic environment during sepsis via pro- and antiinflammatory processes. In case of an unbalanced, dysregulated and radical (in both directions) response mortality become frightfully high. Infectional source control, adequate antibiotic therapy and organ support are the three corner stones in the treatment of sepsis since the definition of sepsis born.In our review we would like to add a detailed overview on two promising modalities of immunomodulation: (1) extracorporeal blood purification; (2) immunostimulation.The purposeof present article is to give an up-to-date, comprehensive review on the utilization of extracorporeal blood purification techniques and immunostimulation in septic patient after cardiac surgery.

Extracorporeal Blood Purification Therapies for Sepsis

Extracorporeal blood purification is proposed as an adjuvant therapy for sepsis, aiming at controlling the associated dysregulation of the immune system, which is known to induce organ dysfunctions. Different therapies have been developed to address certain steps of the immune dysregulation. Most of the available blood purification devices focus on a single target, such as the endotoxin that triggers the immune cascade, or the cytokine storm that causes organ damages. However, the highly adsorptive membrane named oXiris® is a unique 4-in-1 device that combines cytokine and endotoxin removal properties, renal replacement function, and antithrombogenic properties. More recently, promising treatments that focus on the pathogen itself or the immune cells have been developed and are currently under investigation. In this review, we aim to summarize, according to their target, the different extracorporeal blood purification techniques that are already available for use. We will also briefly introduce the most recent techniques that are still under development. Because of its unique ability to remove both endotoxins and cytokines, we will particularly discuss the highly adsorptive preheparinized oXiris® membrane. We will present its properties, advantages, pitfalls, as well as therapeutic perspectives based on experimental and clinical data. Video Journal Club “Cappuccino with Claudio Ronco” at https://www.karger.com/Journal/ArticleNews/223997?sponsor=52

OXiris® Use in Septic Shock: Experience of Two French Centres

Background: Sepsis is a dysregulated host response to an infection and can result in organ dysfunctions and death. Extracorporeal blood purification techniques aim to improve the prognosis of these patients by modulating the unbalanced immune response. This study reports our experience with the use of the oXiris® membrane for septic shock patients requiring continuous renal replacement therapy (CRRT). Summary: Thirty-one patients were diagnosed with septic shock and underwent CRRT with the oXiris® membrane between 2014 and 2019. We compared the observed hospital mortality with that predicted by the Simplified Acute Physiology Score II (SAPS II). Change in the Sequential Organ Failure Assessment (SOFA) score and of the main clinical and biological parameters over time were analyzed. Hospital mortality was lower than predicted for the most severe patients (60 vs. 91% for the [74–87] SAPS II quartile and 70 vs. 98% for the [87–163] SAPS II quartile, p < 0.02). There was no significant improvement in the SOFA score from 0h to 48 h. An 88% relative decrease in norepinephrine infusion was observed (median at 0 h was 1.69 [0.52–2.45] µg/kg/min; at 48 h it was 0.20 [0.09–1.14] µg/kg/min, p = 0.002). Lactataemia and pH were significantly improved over time. Patients with intra-abdominal sepsis as well as those with Gram-negative bacilli (GNB) infections seemed to benefit the most from the therapy. Key Messages: CRRT with the oXiris® haemofilter resulted in higher observed survival than predicted by a severity score (SAPS II) for the most severe patients. Haemodynamic status and lactataemia appeared to improve, especially in intra-abdominal sepsis and GNB infections.

Clinical practice guidelines for the provision of renal service in Hong Kong: General Nephrology.

Clinical practice guidelines for the provision of renal service in Hong Kong: General Nephrology.

Extracorporeal blood purification techniques in children with hyper-inflammatory syndromes: a clinical overview.

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.

Complex intensive care for a patient with septic shock after neurosurgical intervention using a combined extracorporeal blood purification technique

Complex intensive care for a patient with septic shock after neurosurgical intervention using a combined extracorporeal blood purification technique

Systemic anticoagulation during continuous renal replacement therapy – practical aspects

Introduction: Extracorporeal blood purification techniques have become a well-established part of routine practice in intensive therapy units. Ensuring appropriate anticoagulation to prevent the clotting of the circuit is the major concern while applying these techniques. Aim: The aim of this paper is to present methods of systemic anticoagulation which are currently used in continuous extracorporeal blood purification techniques. Ma t e r i a l and me thods : This work is based on the available literature and the experience of the authors. Re sul t s and di s cus s ion: The prevention of clotting in the extracorporeal circuit may be achieved through regional or systemic anticoagulation. Systemic anticoagulation is usually achieved by administration of unfractionated heparin. The most common complications include bleeding; additionally, there is a risk of type II thrombocytopenia occurring. Systemic anticoagulation may also be provided through administration of low molecular weight heparins. Some research papers have discussed the use of thrombin antagonists (argatroban, bivalirudin) and heparinoids (danaparoid, fondaparinux), as well as platelet inhibitors as systemic anticoagulants. It is also possible to conduct extracorporeal blood purification without anticoagulation. C o n c l u s i o n s : The introduction of continuous extracorporeal blood purification techniques into everyday practice of intensive care units has brought many unquestioned benefits to the patients treated in this setting. On the other hand, it means that doctors need to show an in-depth knowledge of the anticoagulation methods. Despite the wider use of regional anticoagulation during continuous renal replacement therapy, systemic anticoagulation is still important. This is especially when therapies with high blood flow are performed and contraindications to citrate use are present.

THERAPEUTIC PLASMA EXCHANGE AND DOUBLE FILTRATION PLASMAPHERESIS IN SEVERE NEUROIMMUNE DISORDERS.

SUMMARYTherapeutic plasma exchange (TPE) is an extracorporeal blood purification technique, which removes large molecular weight particles such as autoantibodies from plasma. TPE is accepted by the American Society for Apheresis as first line treatment for some severe neuroimmune disorders. Double filtration plasmapheresis (DFPP) is a newer technique in which plasma is not entirely removed, only the antibodies, using special filters. High-dose intravenous immunoglobulins are an alternative treatment for these patients but are much more expensive. We reviewed medical records of 20 patients with severe neurological diseases requiring TPE or DFPP. We analyzed the indications, complications and efficacy of these procedures. After completing the procedures, neurological improvement was recorded in 80% of the patients, 5% had no improvement, and the mortality was 15%. The rate of neurological improvement was similar to other studies. None of the patients presented catheter related complications. Systemic complications were mild, transient and completely reversible.

Practical issues of regional anticoagulation during continuous renal replacement therapy

Introduction: Extracorporeal blood purification techniques have become a well-established part of routine practice in intensive care units. The issue of major concern while applying these techniques is to ensure appropriate anticoagulation to prevent the clotting of the circuit. Aim: The aim of this paper is to present regional anticoagulation as a method which is currently used in continuous extracorporeal blood purification techniques. Material and methods: This work is based on the available literature and the authors’ experience. Results and discussion: Anticoagulation used to prevent the clotting of the circuit in extracorporeal blood purification techniques may be regional or systemic. Regional anticoagulation inhibits clotting only in the extracorporeal circuit. In this case either sodium citrate together with calcium substitution or heparin with protamine sulfate is used. Systemic anticoagulation involves the inhibition of clotting in the extracorporeal circuit and in the patient’s body. Regional citrate anticoagulation (RCA) is obtained with the use of citrate. With this technique calcium substitution is necessary in order to prevent hypocalcemia. Other possible complications include alkalosis, metabolic acidosis, hypercalcemia and hypomagnesemia. This paper presents also some practical aspects of regional anticoagulation during continuous renal replacement therapy (CRRT) Conclusions: The application of RCA has contributed to a wider use of CRRT in intensive therapy units. The greatest advantage of this method is almost complete elimination of bleeding complications associated with the therapy. It enables effective blood purification in the patients in whom the use of heparins is contraindicated. This fact has found confirmation in Kidney Disease: Improving Global Outcomes (KDIGO) guidelines.

Timing of renal replacement therapy initiation for acute kidney injury.

Acute kidney injury (AKI) is a common condition among patients in intensive care units (ICUs), and is associated with high death. Renal replacement therapy (RRT) is a blood purification technique used to treat the most severe forms of AKI. The optimal time to initiate RRT so as to improve clinical outcomes remains uncertain.This review complements another Cochrane review by the same authors: Intensity of continuous renal replacement therapy for acute kidney injury. To assess the effects of different timing (early and standard) of RRT initiation on death and recovery of kidney function in critically ill patients with AKI. We searched the Cochrane Kidney and Transplant's Specialised Register to 23 August 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also searched LILACS to 11 September 2017. We included all randomised controlled trials (RCTs). We included all patients with AKI in ICU regardless of age, comparing early versus standard RRT initiation. For safety and cost outcomes we planned to include cohort studies and non-RCTs. Data were extracted independently by two authors. The random-effects model was used and results were reported as risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). We included five studies enrolling 1084 participants. Overall, most domains were assessed as being at low or unclear risk of bias. Compared to standard treatment, early initiation may reduce the risk of death at day 30, although the 95% CI does not rule out an increased risk (5 studies, 1084 participants: RR 0.83, 95% CI 0.61 to 1.13; I2 = 52%; low certainty evidence); and probably reduces the death after 30 days post randomisation (4 studies, 1056 participants: RR 0.92, 95% CI 0.76 to 1.10; I2= 29%; moderate certainty evidence); however in both results the CIs included a reduction and an increase of death. Earlier start may reduce the risk of death or non-recovery kidney function (5 studies, 1076 participants: RR 0.83, 95% CI 0.66 to 1.05; I2= 54%; low certainty evidence). Early strategy may increase the number of patients who were free of RRT after RRT discontinuation (5 studies, 1084 participants: RR 1.13, 95% CI 0.91 to 1.40; I2= 58%; low certainty evidence) and probably slightly increases the recovery of kidney function among survivors who discontinued RRT after day 30 (5 studies, 572 participants: RR 1.03, 95% CI 1.00 to 1.06; I2= 0%; moderate certainty evidence) compared to standard; however the lower limit of CI includes the null effect. Early RRT initiation increased the number of patients who experienced adverse events (4 studies, 899 participants: RR 1.10, 95% CI 1.03 to 1.16; I2 = 0%; high certainty evidence). Compared to standard, earlier RRT start may reduce the number of days in ICU (4 studies, 1056 participants: MD -1.78 days, 95% CI -3.70 to 0.13; I2 = 90%; low certainty evidence), but the CI included benefit and harm. Based mainly on low quality of evidence identified, early RRT may reduce the risk of death and may improve the recovery of kidney function in critically patients with AKI, however the 95% CI indicates that early RRT might worsen these outcomes. There was an increased risk of adverse events with early RRT. Further adequate-powered RCTs using appropriate criteria to define the optimal time of RRT are needed to reduce the imprecision of the results.

Effect of Ionic Strength, pH and Chemical Displacers on the Percentage Protein Binding of Protein-Bound Uremic Toxins

Background and Objectives: While trying to optimize the dialysis clearances of protein-bound uremic toxins (PBUTs), their percentage protein binding (% PB) is an important parameter. We evaluated the effects of ionic strength, pH change and chemical displacers on the dissociation of PBUTs from albumin in vitro. Methods: PBUTs, such as 3-Carboxy-4-methyl-5-propyl-2-furan-propanoic acid (CMPF), p-cresylsulfate (PCS), indoxyl sulfate (IS) and indole-3-acetic acid (IAA), were spiked with human serum albumin (HSA) solution prepared with different Nacl concentrations and pH values or in the presence of a series of chemical displacers. Ultrafiltration was performed to separate the free and bound fractions, and the % PB of each PBUT was calculated. Results: For all 4 compounds, their % PB decreased with increasing ionic strength, while only slight changes occurred when the pH of the test solution increased from pH 6.0 to pH 8.5; PCS, IS and 3-IAA were relatively easily dissociated from albumin by drug displacement, while CMPF was released from HSA by all studied drugs with difficulty; the PB % for CMPF, PCS, IS and 3-IAA decreased most remarkably in the presence of free fatty acids, such as oleic acid (41.73% for CMPF, 29.9% for PCS, 23.22% for IS, and 20.34% for 3-IAA) and linoleic acid (43.12% for CMPF, 16.65% for PCS, 29.99% for IS, and 16.29% for 3-IAA). Conclusion: The protein binding of PBUTs can be decreased by higher ionic strength, increased pH and the presence of some chemical displacers, including free fatty acids. Effective dialytic removal of PBUTs may be achieved by applying these methods jointly to blood-purification techniques.

CRRT for sepsis-induced acute kidney injury.

Sepsis-induced acute kidney injury (SI-AKI) represents the first cause of AKI in ICUs, and renal replacement therapy (RRT) is frequently applied in advanced AKI stages. The debate between 'rescue' indications for RRT start in patients with severe AKI (acidosis, hyperkalemia, uremia, oliguria/anuria, volume overload) and a proactive RRT initiation is still ongoing. In addition, current SI-AKI pathophysiologic theory has identified the toxic effects of soluble middle-molecules released during sepsis and inflammation (pathogen and damaged associated molecular patterns).The purpose of the present review is to summarize the recent literature on RRT for patients with SI-AKI. Supportive or replacement measures for severe stages of renal dysfunction and blood purification techniques for sepsis syndrome will be reviewed. Anticipated RRT for SI-AKI does not seem to improve survival or renal recovery. There is no clinical advantage by delivering continuous RRT at high doses for blood purification purposes. Similarly, specific applications with dedicated devices and membranes have yielded no clinical benefit in these patients, so far. In the present review, the recent insights and results from large randomized and nonrandomized trials in the area of RRT applied both as supportive measures for kidney failure and blood purification techniques are described.