Dataset Information

Outcomes of Kidney Transplantation in Highly HLA-Sensitized Patients Treated with Intravenous Immuno-Globulin, Plasmapheresis and Rituximab: A Meta-Analysis.

ABSTRACT: (1) Background: We aimed to investigate the outcomes of human leukocyte antigen (HLA)-incompatible transplantation for patients who received desensitization with intravenous immunoglobulins (IVIg), plasmapheresis, and rituximab. (2) Methods: A comprehensive search of multiple electronic databases to identify studies that utilized desensitization was conducted. The random-effects model was used to calculate the pooled rates and the 95% confidence interval (CI). (3) Results: A total of 1517 studies were initially identified. From these, 16 studies met the inclusion criteria, encompassing 459 patients, with a mean age of 45 years, of whom 40.8% were male. CDC crossmatch was positive in 68.3% (95% CI: 43.5-85.8; I2 87%), and 89.4% (95% CI: 53.4-98.4%; I2 89.8%) underwent living-donor transplantation. The 1-year graft survival pooled rate was 88.9% (95% CI: 84.8-92; I2 0%) and the 5-year graft survival rate was 86.1% (95% CI: 81.2-89.9; I2 0%). The 1-year patient survival rate was 94.2% (95% CI: 91-96.3; I2 0%), and the 5-year patient survival rate was 88.9% (95% CI: 83.5-92.7%; I2 7.7%). The rate of antibody-mediated rejection was 37.7% (95% CI: 25-52.3; I2 80.3%), and the rate of acute cell-mediated rejection was 15.1% (95% CI: 9.1-24; I2 55%). (4) Conclusions: Graft and patient survival are favorable in highly sensitized patients who undergo desensitization using IVIg, plasmapheresis, and rituximab for HLA-incompatible transplantation.

SUBMITTER: Chandramohan D

PROVIDER: S-EPMC11355159 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Outcomes of Kidney Transplantation in Highly HLA-Sensitized Patients Treated with Intravenous Immuno-Globulin, Plasmapheresis and Rituximab: A Meta-Analysis.

Chandramohan Deepak D Adisa Oluwadamilola O Patel Devansh D Ware Erin E Eleti Navya N Agarwal Gaurav G

Life (Basel, Switzerland) 20240810 8

(1) Background: We aimed to investigate the outcomes of human leukocyte antigen (HLA)-incompatible transplantation for patients who received desensitization with intravenous immunoglobulins (IVIg), plasmapheresis, and rituximab. (2) Methods: A comprehensive search of multiple electronic databases to identify studies that utilized desensitization was conducted. The random-effects model was used to calculate the pooled rates and the 95% confidence interval (CI). (3) Results: A total of 1517 studie ...[more]

PMID: 39202740

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Project description:Background: We aimed to investigate the effects of intravenous immune globulin (IVIG) and rituximab desensitization treatment on kidney transplant rate and blood gene expression profiles by microrarrays. Methods: We enrolled patients with PRA levels >50% and on the deceased-donor waiting list for >5 years. Patients received IVIG (2.0 g/kg) on day 0 and 30; and rituximab (375 mg/m2) on day 15. The antibodies with mean fluorescence intensity (MFI) values > 5,000 were reported to UNET as unacceptable antigens. The gene expression profiles of blood samples collected in PAXGene tube were studied by Affymetrix HuGene 1.0 ST expression arrays. Results: 40 of the 415 patients (10%) on the waiting list were eligible for desensitization treatment and 11 completed the treatment. While 15 of the remaining 29 patients (52%) received a transplant without therapy, only 2 of the 11 desensitized patients (18%) received transplant during a median follow-up of 217 days. While there were no statistically significant difference in demographics, desensitized patients had higher cPRA values (97% vs. 77%, p=0.0005) and more number of unacceptable antigens (39 vs. 10, p=0.0001). There was no significant change in the mean number of unacceptable antigens (39 ± 22 versus 39 ± 23) or reduction in the mean MFI values (11,333 ± 3,133 vs 11,289 ± 3,386). Analysis of genes chosen as significantly differentially expressed revealed downregulation of genes involved in B cells and immune system (CD79a, B and T lymphocyte associated transcript, B cell scaffold protein, CD22, CXCR5, fas apoptotic inhibitory protein). Gene set enrichment analysis using Pathogenesis Based Transcripts created by Edmonton Group demonstrated significant downregulation of B cell associated (p=0.04) and immunoglobulin transcripts (p=0.03). Conclusion: Although, desensitization with IVIG and rituximab decreases the expression of B cell and immunoglobulin associated transcripts, it was not successful in increasing kidney transplant rate or in decreasing the number of unacceptable antigens.

Project description:BackgroundFocal 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.AimTo 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.MethodsThis 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.ResultsEleven 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.ConclusionOverall, 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.

Project description:BACKGROUND:We investigated in vitro whether HLA highly sensitized patients with end-stage renal disease will be disadvantaged immunologically after a genetically engineered pig kidney transplant. METHODS:Blood was drawn from patients with a calculated panel-reactive antibody (cPRA) 99% to 100% (Gp1, n = 10) or cPRA 0% (Gp2, n = 12), and from healthy volunteers (Gp3, n = 10). Serum IgM and IgG binding was measured (i) to galactose-α1-3 galactose and N-glycolylneuraminic acid glycans by enzyme-linked immunosorbent assay, and (ii) to pig red blood cell, pig aortic endothelial cells, and pig peripheral blood mononuclear cell from α1,3-galactosyltransferase gene-knockout (GTKO)/CD46 and GTKO/CD46/cytidine monophosphate-N-acetylneuraminic acid hydroxylase-knockout (CMAHKO) pigs by flow cytometry. (iii) T-cell and B-cell phenotypes were determined by flow cytometry, and (iv) proliferation of T-cell and B-cell carboxyfluorescein diacetate succinimidyl ester-mixed lymphocyte reaction. RESULTS:(i) By enzyme-linked immunosorbent assay, there was no difference in IgM or IgG binding to galactose-α1-3 galactose or N-glycolylneuraminic acid between Gps1 and 2, but binding was significantly reduced in both groups compared to Gp3. (ii) IgM and IgG binding in Gps1 and 2 was also significantly lower to GTKO/CD46 pig cells than in healthy controls, but there were no differences between the 3 groups in binding to GTKO/CD46/CMAHKO cells. (iii and iv) Gp1 patients had more memory T cells than Gp2, but there was no difference in T or B cell proliferation when stimulated by any pig cells. The proliferative responses in all 3 groups were weakest when stimulated by GTKO/CD46/CMAHKO pig peripheral blood mononuclear cell. CONCLUSIONS:(i) End-stage renal disease was associated with low antipig antibody levels. (ii) Xenoreactivity decreased with increased genetic engineering of pig cells. (iii) High cPRA status had no significant effect on antibody binding or T-cell and B-cell response.

Project description:BackgroundKidney transplantation is the most effective treatment for end-stage kidney disease. Sensitization, the formation of human leukocyte antigen (HLA) antibodies, remains a major barrier to successful kidney transplantation. Despite the implementation of desensitization strategies, many candidates fail to respond. Current progress is hindered by the lack of biomarkers to predict response and to guide therapy. Our objective was to determine whether differences in immune and gene profiles may help identify which candidates will respond to desensitization therapy.Methods and findingsSingle-cell mass cytometry by time-of-flight (CyTOF) phenotyping, gene arrays, and phosphoepitope flow cytometry were performed in a study of 20 highly sensitized kidney transplant candidates undergoing desensitization therapy. Responders to desensitization therapy were defined as 5% or greater decrease in cumulative calculated panel reactive antibody (cPRA) levels, and non-responders had 0% decrease in cPRA. Using a decision tree analysis, we found that a combination of transitional B cell and regulatory T cell (Treg) frequencies at baseline before initiation of desensitization therapy could distinguish responders from non-responders. Using a support vector machine (SVM) and longitudinal data, TRAF3IP3 transcripts and HLA-DR-CD38+CD4+ T cells could also distinguish responders from non-responders. Combining all assays in a multivariate analysis and elastic net regression model with 72 analytes, we identified seven that were highly interrelated and eleven that predicted response to desensitization therapy.ConclusionsMeasuring baseline and longitudinal immune and gene profiles could provide a useful strategy to distinguish responders from non-responders to desensitization therapy. This study presents the integration of novel translational studies including CyTOF immunophenotyping in a multivariate analysis model that has potential applications to predict response to desensitization, select candidates, and personalize medicine to ultimately improve overall outcomes in highly sensitized kidney transplant candidates.

Dataset Information

Outcomes of Kidney Transplantation in Highly HLA-Sensitized Patients Treated with Intravenous Immuno-Globulin, Plasmapheresis and Rituximab: A Meta-Analysis.

Publications

Outcomes of Kidney Transplantation in Highly HLA-Sensitized Patients Treated with Intravenous Immuno-Globulin, Plasmapheresis and Rituximab: A Meta-Analysis.

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