A randomized controlled trial of preemptive rituximab to prevent recurrent focal segmental glomerulosclerosis post-kidney transplant (PRI-VENT FSGS): protocol and study design
Frontiers in nephrology. 2023;3:1181076
BACKGROUND Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease requiring kidney transplantation and can recur in the allograft in 30-80% of recipients resulting in reduced graft survival. Plasmapheresis has shown efficacy in treating some cases of recurrent FSGS but isolated plasmapheresis has not demonstrated efficacy in preventing recurrent FSGS. Rituximab has had anecdotal success in preventing recurrence in a single center study but has not been studied in combination with plasmapheresis for preventing FSGS recurrence. METHODS We are conducting a randomized, controlled, multicenter clinical trial of adult and pediatric kidney transplant recipients with primary FSGS to assess whether plasmapheresis in combination with rituximab prevents recurrent disease post-transplantation. DISCUSSION Rituximab combined with plasmapheresis is a promising, novel therapy to prevent recurrent FSGS, a disease with limited therapeutic options and no consensus guidelines for prevention or treatment. CLINICAL TRIAL REGISTRATION https://clinicaltrials.gov/ct2/show/NCT03763643, identifier NCT03763643.
Efficacy and Economic Evaluation of Nonbiological Artificial Liver Therapy in Acute-on-chronic Hepatitis B Liver Failure
Journal of clinical and translational hepatology. 2023;11(2):433-440
BACKGROUND AND AIMS Nonbiological artificial liver (NBAL) is frequently used as a first-line treatment for hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF). This study aimed to compare the therapeutic efficacy and cost-effectiveness ratio (CER) of comprehensive medical treatment, plasma exchange (PE), and double plasma molecular adsorption system (DPMAS) plus half-dose PE (DPMAS+PE) in patients with HBV-ACLF. METHODS A total of 186 patients with HBV-ACLF randomly received comprehensive medical treatment, PE, or DPMAS+PE and were prospectively evaluated. Patients were divided into four subgroups based on the pretreatment prothrombin activity (PTA): Group I (PTA>40%), group II (PTA 30-40%), group III (PTA 20-30%), and group IV (PTA<20%). The main outcome measures were 28 day effectiveness; 90 day liver transplantation-free survival; change of biochemical parameters; and CER. RESULTS DPMAS+PE treatment was associated with significantly higher 28 day effectiveness and 90 day liver transplantation-free survival compared with PE treatment in patients with group I liver failure. Clearance of serum total bilirubin (TBIL), AST, and creatinine (Cr) were significantly higher in the DPMAS+PE group than in the PE group. For subjects with group I liver failure, DPMAS+PE treatment had advantages of lower CER values and better cost-effectiveness. CONCLUSIONS Compared with comprehensive medical treatment and PE alone, DPMAS with half-dose sequential PE treatment more effectively improved TBIL, AST, and Cr in HBV-ACLF patients, improved 28 day effectiveness and 90 day survival rates in patients with group I liver failure, and was more cost effective. DPMAS+PE is a viable NBAL approach for treatment of HBV-ACLF.
Rituximab or plasmapheresis for prevention of recurrent focal segmental glomerulosclerosis after kidney transplantation: A systematic review and meta-analysis
World journal of transplantation. 2021;11(7):303-319
BACKGROUND Focal segmental glomerulosclerosis (FSGS) is one of the most common glomerular diseases leading to renal failure. FSGS has a high risk of recurrence after kidney transplantation. Prevention of recurrent FSGS using rituximab and/or plasmapheresis has been evaluated in multiple small studies with conflicting results. AIM: To assess the risk of recurrence of FSGS after transplantation using prophylactic rituximab with or without plasmapheresis, and plasmapheresis alone compared to the standard treatment group without preventive therapy. METHODS This meta-analysis and systematic review were performed by first conducting a literature search of the MEDLINE, EMBASE, and Cochrane databases, from inception through March 2021; search terms included 'FSGS,' 'steroid-resistant nephrotic syndrome', 'rituximab,' and 'plasmapheresis,'. We identified studies that assessed the risk of post-transplant FSGS after use of rituximab with or without plasmapheresis, or plasmapheresis alone. Inclusion criteria were: Original, published, randomized controlled trials or cohort studies (either prospective or retrospective), case-control, or cross-sectional studies; inclusion of odds ratio, relative risk, and standardized incidence ratio with 95% confidence intervals (CI), or sufficient raw data to calculate these ratios; and subjects without interventions (controls) being used as comparators in cohort and cross-sectional studies. Effect estimates from individual studies were extracted and combined using a random effects model. RESULTS Eleven studies, with a total of 399 kidney transplant recipients with FSGS, evaluated the use of rituximab with or without plasmapheresis; thirteen studies, with a total of 571 kidney transplant recipients with FSGS, evaluated plasmapheresis alone. Post-transplant FSGS recurred relatively early. There was no significant difference in recurrence between the group that received rituximab (with or without plasmapheresis) and the standard treatment group, with a pooled risk ratio of 0.82 (95%CI: 0.47-1.45, I (2) = 65%). Similarly, plasmapheresis alone was not associated with any significant difference in FSGS recurrence when compared with no plasmapheresis; the pooled risk ratio was 0.85 (95%CI: 0.60-1.21, I (2) = 23%). Subgroup analyses in the pediatric and adult groups did not yield a significant difference in recurrence risk. We also reviewed and analyzed post-transplant outcomes including timing of recurrence and graft survival. CONCLUSION Overall, the use of rituximab with or without plasmapheresis, or plasmapheresis alone, is not associated with a lower risk of FSGS recurrence after kidney transplantation. Future studies are required to assess the effectiveness of rituximab with or without plasmapheresis among specific patient subgroups with high-risk for FSGS recurrence.
Plasma exchange in patients with acute and acute-on-chronic liver failure: A systematic review
World journal of gastroenterology. 2020;26(2):219-245
BACKGROUND Acute liver failure (ALF) and acute-on-chronic liver (ACLF) carry high short-term mortality rate, and may result from a wide variety of causes. Plasma exchange has been shown in a randomized control trial to improve survival in ALF especially in patients who did not receive a liver transplant. Other cohort studies demonstrated potential improvement in survival in patients with ACLF. AIM: To assess utility of plasma exchange in liver failure and its effect on mortality in patients who do not undergo liver transplantation. METHODS Databases MEDLINE via PubMed, and EMBASE were searched and relevant publications up to 30 March, 2019 were assessed. Studies were included if they involved human participants diagnosed with liver failure who underwent plasma exchange, with or without another alternative non-bioartificial liver assist device. RESULTS Three hundred twenty four records were reviewed, of which 62 studies were found to be duplicates. Of the 262 records screened, 211 studies were excluded. Fifty-one articles were assessed for eligibility, for which 7 were excluded. Twenty-nine studies were included for ALF only, and 9 studies for ACLF only. Six studies included both ALF and ACLF patients. A total of 44 publications were included. Of the included publications, 2 were randomized controlled trials, 14 cohort studies, 12 case series, 16 case reports. All of three ALF studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange. In two out of four studies where plasma exchange-based liver support systems were compared to standard medical treatment (SMT) for ACLF, a biochemical improvement was seen. Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs SMT. Using the aforementioned studies, plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60 (95%CI 0.46-0.77, P < 0.01). CONCLUSION The level of evidence for use of high volume plasma exchange in selected ALF cases is high. Plasma exchange in ACLF improves survival at 30-and 90-d in non-transplanted patients. Further well-designed randomized control trials will need to be carried out to ascertain the optimal duration and amount of plasma exchange required and assess if the use of high volume plasma exchange can be extrapolated to patients with ACLF.
Adults and paediatric patients diagnosed with liver failure (44 studies).
Plasma exchange with or without other alternative liver support systems.
Standard medical treatment (SMT).
The acute liver failure (ALF) studies which looked at survival rate or survival days reported improvement in outcome with plasma exchange. In two out of four studies where plasma exchange-based liver support systems were compared to SMT for acute-on-chronic liver (ACLF), a biochemical improvement was seen. Survival in the non-transplanted patients was improved in all four studies in patients with ACLF comparing plasma exchange vs SMT. Using the aforementioned studies, plasma exchange based therapy in ACLF compared to SMT improved survival in non-transplanted patients at 30 and 90-d with a pooled OR of 0.60.
Surface Antigens on Plasma Extracellular Vesicles of Cystic Fibrosis Patients Treated by Extracorporeal Photopheresis as Induction Therapy after Lung Transplantation: Preliminary Results of a Pilot Randomized Trial
J Heart Lung Transplant. 2020;39(4s):S358
PURPOSE Acute rejection (AR) is common during the first year after lung transplantation (LuTx) and can trigger chronic rejection (CR), the leading cause of late morbidity and mortality of LuTx. Extracorporeal photopheresis (ECP) is a promising treatment for chronic rejection. Few studies focus on ECP as prophylactic therapy of AR and CR. Microvesicles and exosomes (i.e.extracellular vesicles EV) are released into the blood and in bronchoalveolar lavage (BAL) and their role in cell-to-cell communication has been assessed in several studies; EV have been proposed as non-invasive biomarkers to assess lung injury and monitor clinical outcome. METHODS We conduct a pilot clinical trial on 24 cystic fibrosis patients undergoing LuTx, randomly allocated in 2 parallel arms: standard immunosuppressive therapy and ECP (ECP) vs standard immunosuppressive therapy alone (CTR). EV concentration was assessed at different time points in blood and BAL in the first year after LuTx (analyzed by nanoparticle tracking analysis Nanosight NS300, Malvern). EV were analyzed for antigen expression with MACSplex bead-based assay. AR episodes and infections were recorded, as far as ECP-related adverse events. Preliminary data on the first 18 patients (9 ECP and 9 CTR) are reported RESULTS ECP was well tollerated and no adverse events or AR occurred in either groups. EV presented highly polydispersed size distributions in a 50-1000 nm range. The expression of EV-associated markers CD63, CD9 and CD81 was detected. Upregulation of platelets (CD62p; p<0.05 by t-test), lymphocytes (CD3, CD24) markers and integrins (CD29, CD49e) was observed in ECP-treated patient compared to the control group. CONCLUSION The underlying mechanism of ECP remains unresolved. The identification of specific EV antigen signatures may represent a promising approach to better understand the immunomodulatory effects of ECP, both at molecular and cellular level.
Effects of platelet-rich plasmapheresis during cardiovascular surgery: A meta-analysis of randomized controlled clinical trials
Journal of clinical anesthesia. 2019;56:88-97
OBJECTIVE This study aimed to explore the effects of platelet-rich plasmapheresis (PRP) on the amount of postoperative blood loss and the requirements for allogeneic fresh frozen plasma (FFP) and red blood cell (RBC) transfusions during cardiovascular surgery. METHODS A literature search of 7 online databases was conducted. Randomized control trials (RCT) comparing intraoperative PRP or appropriate control groups were considered suitable for this current study. RESULTS Fifteen RCTs enrolling a total of 1002 patients, including 501 patients who received PRP and 501 control patients. Meta-analysis of the data from these trials showed that PRP reduced the total volume of postoperative blood loss (standardized mean difference [SMD], -0.74; 95% confidence interval [CI], -1.18 to -0.31; P<0.05), reduced postoperative fresh frozen plasma (FFP) transfusion (SMD, -0.38; 95%CI, -0.69 to -0.08; P<0.05), reduced postoperative RBCs transfusion (SMD, -0.44; 95%CI, -0.77 to -0.10; P<0.05), and reduced the proportion of patients receiving postoperative allogeneic RBC transfusions (relative risk [RR], 0.44; 95%CI, 0.21-0.91, P<0.05) during cardiovascular surgery. CONCLUSION Conducting PRP before cardiopulmonary bypass (CPB) and transfusing autologous platelet-rich plasma (aPRP) after reversal of heparin could reduce postoperative blood loss, the requirements for blood products transfusion during cardiovascular surgery. A higher mean platelet count in aPRP may improve the final outcome. However, there was a high degree of undetermined heterogeneity among the analyzed trials, and larger and more precise RCTs are needed to confirm these conclusions.
Platelet-rich-plasmapheresis for minimising peri-operative allogeneic blood transfusion
Cochrane Database of Systematic Reviews. 2011;((3):):CD004172.
BACKGROUND Concerns regarding the safety of transfused blood have generated considerable enthusiasm for the use of technologies intended to reduce the use of allogeneic blood (blood from an unrelated donor). Platelet-rich plasmapheresis (PRP) offers an alternative approach to blood conservation. OBJECTIVES To examine the evidence for the efficacy of PRP in reducing peri-operative allogeneic red blood cell (RBC) transfusion, and the evidence for any effect on clinical outcomes such as mortality and re-operation rates. SEARCH STRATEGY We identified studies by searching MEDLINE (1950 to 2009), EMBASE (1980 to 2009), The Cochrane Library (Issue 1, 2009), the Internet (to March 2009) and the reference lists of published articles, reports, and reviews. SELECTION CRITERIA Controlled parallel group trials in which adult patients, scheduled for non-urgent surgery, were randomised to PRP, or to a control group which did not receive the intervention. DATA COLLECTION AND ANALYSIS Primary outcomes measured were: the number of patients exposed to allogeneic RBC transfusion, and the amount of RBC transfused. Other outcomes measured were: the number of patients exposed to allogeneic platelet transfusions, fresh frozen plasma, and cryoprecipitate, blood loss, re-operation for bleeding, post-operative complications (thrombosis), mortality, and length of hospital stay. Treatment effects were pooled using a random-effects model. Trial quality was assessed using criteria proposed by Schulz et al (Schulz 1995). MAIN RESULTS Twenty-two trials of PRP were identified that reported data for the number of patients exposed to allogeneic RBC transfusion. These trials evaluated a total of 1589 patients. The relative risk (RR) of exposure to allogeneic blood transfusion in those patients randomised to PRP was 0.73 (95%CI 0.59 to 0.90), equating to a relative risk reduction (RRR) of 27% and a risk difference (RD) of 19% (95%CI 10% to 29%). However, significant heterogeneity of treatment effect was observed (p < 0.00001; I2 = 79%). When the four trials by Boldt are excluded, the RR is 0.76 (95% CI 0.62 to 0.93). On average, PRP did not significantly reduce the total volume of RBC transfused (weighted mean difference [WMD] -0.69, 95%CI -1.93 to 0.56 units). Trials provided inadequate data regarding the impact of PRP on morbidity, mortality, and hospital length of stay. Trials were generally small and of poor methodological quality. AUTHORS' CONCLUSIONS Although the results suggest that PRP is effective in reducing allogeneic RBC transfusion in adult patients undergoing elective surgery, there was considerable heterogeneity of treatment effects and the trials were of poor methodological quality. The available studies provided inadequate data for firm conclusions to be drawn regarding the impact of PRP on clinically important endpoints.
Effectiveness of combining plasma exchange and continuous hemodiafiltration in patients with postoperative liver failure
Artificial Organs. 2005;29((4):):324-8.
Nine patients with postoperative liver failure were treated with plasma exchange (PE) or PE and continuous hemodiafiltration (CHDF), and various biochemical parameters were determined before and after treatment. Although citrate levels increased significantly after treatment compared with pretreatment levels in both the PE group and the PE + CHDF group (P < 0. 0001 and P < 0. 0001, respectively), the percentage of the increase in citrate levels was significantly higher in the PE group than in the PE + CHDF group (P = 0. 0051). Total bilirubin (T-Bil) levels were significantly lower after treatment in both the PE and PE + CHDF groups (P < 0. 0001 and P = 0. 0001, respectively). There were no significant differences in T-Bil levels between the two groups (P = 0. 5181). There were no significant differences in interleukin (IL)-6 levels before and after treatment in both the PE and PE + CHDF groups (P = 0. 1281 and P = 0. 2273, respectively). IL-18 levels were significantly lower after treatment in both the PE and PE + CHDF groups (P < 0. 0001 and P = 0. 0002, respectively), but there were no significant differences in the removal rate of IL-18 in both the PE and PE + CHDF groups (P = 0. 8749). These results indicate that combining PE and CHDF in a series-parallel circuit is an effective modality for suppressing the elevation of blood citrate levels. This finding may have important implications for the development of an effective treatment for patients with postoperative liver failure.
Intraoperative use of platelet-plasmapheresis in vascular surgery
Journal of Clinical Anesthesia. 2002;14((1):):10-4.
STUDY OBJECTIVE To determine, in a pilot study, whether pheresis of plasma and platelets before surgical blood loss, with reinfusion of the autologous plasma and platelets after completion of the aortic reconstruction, will result in decreased bleeding and decreased transfusion of allogenic blood components in patients undergoing elective aortic reconstruction. DESIGN Randomized study. SETTING University medical center. INTERVENTIONS Patients were randomized to perioperative (acute) platelet plasmapheresis (APP group) versus conventional blood component therapy (control group). In the APP group, blood was withdrawn after induction of anesthesia, to sequester approximately 300 mL of platelet rich plasma (PRP); platelet poor plasma (PPP) and red blood cells (RBC) were sequestered as well. An autotransfusion device was used to collect and re-infuse autologous RBC during the course of the operation in both groups. After completion of the aortic reconstruction, autologous PRP and PPP were re-infused in the APP group. Blood loss, volume of blood component transfusions, and preoperative and postoperative hemoglobin (Hb), hematocrit (Hct), platelet, international normalized ratio (INR), and activated partial thromboplastin time (aPTT) were recorded. MEASUREMENTS AND MAIN RESULTS There was no difference between groups in demographics, preoperative laboratory values, or surgical procedures, although more patients were treated for aneurysms (73% vs. 60%) and fewer for occlusive disease (20% vs. 40%) in the control versus APP group. Also, there were no differences between the control and APP groups in duration of operation, blood loss, volume of colloid infused, or volume of allogenic RBC and plasma transfused. Patients in the APP group received a greater volume of crystalloid solution (9.1 +/- 3.4 L vs. 6.8 +/- 3.0 L; p = 0.002), but fewer units of allogenic platelets than the control group (0.7 +/- 1.0 units vs. 0.2 +/- 0.4 units; p < 0.04). There were no differences in postoperative Hb, Hct, INR, aPTT, or fibrinogen. The platelet count was lower in the APP group than in the control group (123 +/- 40 x 10(3)/mm(3) vs. 182 +/- 51 x 10(3)/mm(3); p = 0.004). CONCLUSIONS Perioperative platelet plasmapheresis led to fewer allogenic platelet transfusions in patients undergoing elective aortic reconstruction. However, there was no decrease in blood loss and no reduction in transfusion of allogenic RBC or plasma. Perioperative platelet plasmapheresis is not recommended for routine use in elective aortic reconstruction.
The role of rheology in hemapheresis
Therapeutic Apheresis. 2001;5((2):):128-33.
Rheological therapy attempts to favorably influence the blood flow mechanics for the treatment of diseases, mainly of the microcirculation but also of the macrocirculation. Hemapheresis, originally used only for the elimination of an excess of cellular or plasmatic components, was shown to also influence the hemorheology favorably. As extracorporeal therapy affects the rheology much more than conventional hemorheotherapy, not only cellular or plasmatic hyperviscosity syndromes but also many more diseases associated with organ perfusion problems due to diseases of the micro- and macrocirculation, especially in the elderly, were and are increasingly considered to be indicated. Technical progress led away from plasma exchange as an unspecific and unselective procedure to plasma differential separation using precipitation. adsorption, and filtration. With our recent development, we demonstrated that rheohemapheresis is the most advanced technical procedure. The mechanism of action can well be related to a synergetic consideration of rheology. However. one has to keep in mind that the elimination of blood components such as lipids, immunoglobulins, and endothelial factors may well contribute to the explanation and understanding of the positive clinical effects observed. These speculative aspects need further investigation.