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.
Bedside Allogeneic Erythrocyte Washing with a Cell Saver to Remove Cytokines, Chemokines, and Cell-derived Microvesicles
BACKGROUND Removal of cytokines, chemokines, and microvesicles from the supernatant of allogeneic erythrocytes may help mitigate adverse transfusion reactions. Blood bank-based washing procedures present logistical difficulties; therefore, we tested the hypothesis that on-demand bedside washing of allogeneic erythrocyte units is capable of removing soluble factors and is feasible in a clinical setting. METHODS There were in vitro and prospective, observation cohort components to this a priori planned substudy evaluating bedside allogeneic erythrocyte washing, with a cell saver, during cardiac surgery. Laboratory data were collected from the first 75 washed units given to a subset of patients nested in the intervention arm of a parent clinical trial. Paired pre- and postwash samples from the blood unit bags were centrifuged. The supernatant was aspirated and frozen at -70°C, then batch-tested for cell-derived microvesicles, soluble CD40 ligand, chemokine ligand 5, and neutral lipids (all previously associated with transfusion reactions) and cell-free hemoglobin (possibly increased by washing). From the entire cohort randomized to the intervention arm of the trial, bedside washing was defined as feasible if at least 75% of prescribed units were washed per protocol. RESULTS Paired data were available for 74 units. Washing reduced soluble CD40 ligand (median [interquartile range]; from 143 [1 to 338] ng/ml to zero), chemokine ligand 5 (from 1,314 [715 to 2,551] to 305 [179 to 488] ng/ml), and microvesicle numbers (from 6.90 [4.10 to 20.0] to 0.83 [0.33 to 2.80] × 106), while cell-free hemoglobin concentration increased from 72.6 (53.6 to 171.6) mg/dl to 210.5 (126.6 to 479.6) mg/dl (P < 0.0001 for each). There was no effect on neutral lipids. Bedside washing was determined as feasible for 80 of 81 patients (99%); overall, 293 of 314 (93%) units were washed per protocol. CONCLUSIONS Bedside erythrocyte washing was clinically feasible and greatly reduced concentrations of soluble factors thought to be associated with transfusion-related adverse reactions, increasing concentrations of cell-free hemoglobin while maintaining acceptable (less than 0.8%) hemolysis.
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.
[The long-term infective complications in patients after kidney transplantation and photopheresis]
Urologiia (Moscow, Russia : 1999). 2018;(5):28-34
AIM: to evaluate the influence of prophylactic use of photopheresis on the risk of long-term infective complications after kidney transplantation. MATERIALS AND METHODS The open cohort randomized study was conducted. A total of 60 recipients after cadaveric kidney allotransplantation from 30 donors were assessed. The patients were randomized into two groups (n=30). All transplants were paired, and one kidney was transplanted to patient in intervention group and the another one was transplanted to patient in control group. In the intervention group all patients received standard immunosuppression therapy (tacrolimus, mycophenolate, prednisone) and 10-15 sessions of photopheresis during first 6 months after the transplantation. In the control group only the immunosuppression therapy was given. The follow-up period ranged from 2 to 7 years, an average 4.5+/-2.0 years. RESULTS The rate infective complications in the both groups gradually decreased as the postoperative period increased exponentially, but it was lower in the intervention group than in the control group. The rate of respiratory infection, asymptomatic bacteriuria and viremia, verified by the genetic amplification was 4, 2 and 1.5 times lower in the intervention group. The risk of clinically meaningful infection was significantly lower in the intervention group than in the control group: IRR 0.3888 (95% CI 0.2754; 0.5445; <0.0001). 6-year survival in the intervention group was 100% in comparison to 82.8% in the control group (95% CI 51.6; 93.16). CONCLUSION The prophylactic use of the photopheresis allows to decrease the risk of infective complications after the kidney transplantation.
Cold-stored apheresis platelets in treatment of postoperative bleeding in cardiothoracic surgery
Transfusion. 2016;56((S4)):16A.. s29-020b.
The effects of platelet apheresis on blood saving and coagulation in bilateral total hip replacement: a prospective study on 60 patients
International Journal of Surgery (London, England). 2016;34:58-63
BACKGROUND Preoperative platelet rich plasma (PRP) harvest has been used in cardiopulmonary surgery for more than 10 years. There is no previous study dealing with PRP in bilateral total hip replacement. This study was to investigate the effects of PRP on blood saving and blood coagulation function in patients with bilateral total hip replacement. PATIENTS AND METHODS A prospective, randomized, clinical trial was conducted. Sixty patients were enrolled, including 30 patients undergoing PRP in the PRP group and 30 controls. The surgery time, total transfusion volume, blood loss, allogenic blood transfusion, autologous blood transfusion, urine volume, drainage volume, some blood parameters (including Fibrinogen, D-dimer, Prothrombin time, international normalizedratio, activated partial thromboplastin time, Platelet, Haemoglobin B), thrombelastogram (TEG) and blood-gas parameters were studied in the perioperative stage. The measurement data were analyzed statistically. RESULTS There was no statistical difference between the two groups in baseline characteristics, surgery time, total transfusion volume, blood loss, autologous blood transfusion, etc. Allogenic blood transfusion in the PRP group was less than the control group with statistical difference (p=0.024). Fibrinogen in the PRP group was higher than the control group (p=0.008). Among the TEG indicators, activated clotting time and coagulation time K in the PRP group were less than the control group. Clotting rate and maximum amplitude in the PRP group were higher. The blood-gas parameters presented no statistical difference. CONCLUSION The results suggested that PRP probably played a positive role in blood coagulation function as well as blood saving in patients with bilateral total hip replacement.