Alicia B Lichvar1, Simon Tremblay2,3, Abbie D Leino4, Adele R Shields2,5, Michael A Cardi5, Bassam G Abu Jawdeh6, Amit Govil6, Joseph Kremer5, Madison Cuffy2, Flavio Paterno7, Tayyab Diwan2, Paul Brailey8, Alin Girnita8, Rita R Alloway6, E Steve Woodle2. 1. Department of Pharmacy Practice and Surgery, University of Illinois at Chicago, Chicago, IL. 2. Department of Surgery, Division of Transplantation, University of Cincinnati, Cincinnati, OH. 3. Department of Environmental Health, Division of Epidemiology, University of Cincinnati, Cincinnati, OH. 4. Department of Pharmacy, The Ohio State University Wexner Medical Center, Columbus, OH. 5. The Christ Hospital, Cincinnati, OH. 6. Department of Internal Medicine, Division of Nephrology, University of Cincinnati, Cincinnati, OH. 7. Division of Liver Transplantation and Hepatobiliary Surgery, Rutgers New Jersey Medical School, Newark, NJ. 8. Transplant Immunology Division, Hoxworth Blood Center, University of Cincinnati, Cincinnati, OH.
Abstract
BACKGROUND: Reduction in donor-specific antibody (DSA) has been associated with improved renal allograft survival after antibody-mediated rejection (AMR). These observations have not been separately analyzed for early and late AMR and mixed acute rejection (MAR). The purpose of this study was to evaluate long-term responses to proteasome inhibitor-based therapy for 4 rejection phenotypes and to determine factors that predict allograft survival. METHODS: Retrospective cohort study evaluating renal transplant recipients with first AMR episodes treated with proteasome inhibitor-based therapy from January 2005 to July 2015. RESULTS: A total of 108 patients were included in the analysis. Immunodominant DSA reduction at 14 days differed significantly (early AMR 79.6%, early MAR 54.7%, late AMR 23.4%, late MAR 21.1%, P < 0.001). Death-censored graft survival (DCGS) differed at 3 years postrejection (early AMR 88.3% versus early MAR 77.8% versus late AMR 56.7% versus late MAR 54.9%, P = 0.02). Multivariate analysis revealed that immunodominant DSA reduction > 50% at 14 days was associated with improved DCGS (odds ratio, 0.12, 95% CI, 0.02-0.52, P = 0.01). CONCLUSIONS: In summary, significant differences exist across rejection phenotypes with respect to histological and DSA responses. The data suggest that DSA reduction may be associated with improved DCGS in both early and late AMR.
BACKGROUND: Reduction in donor-specific antibody (DSA) has been associated with improved renal allograft survival after antibody-mediated rejection (AMR). These observations have not been separately analyzed for early and late AMR and mixed acute rejection (MAR). The purpose of this study was to evaluate long-term responses to proteasome inhibitor-based therapy for 4 rejection phenotypes and to determine factors that predict allograft survival. METHODS: Retrospective cohort study evaluating renal transplant recipients with first AMR episodes treated with proteasome inhibitor-based therapy from January 2005 to July 2015. RESULTS: A total of 108 patients were included in the analysis. Immunodominant DSA reduction at 14 days differed significantly (early AMR 79.6%, early MAR 54.7%, late AMR 23.4%, late MAR 21.1%, P < 0.001). Death-censored graft survival (DCGS) differed at 3 years postrejection (early AMR 88.3% versus early MAR 77.8% versus late AMR 56.7% versus late MAR 54.9%, P = 0.02). Multivariate analysis revealed that immunodominant DSA reduction > 50% at 14 days was associated with improved DCGS (odds ratio, 0.12, 95% CI, 0.02-0.52, P = 0.01). CONCLUSIONS: In summary, significant differences exist across rejection phenotypes with respect to histological and DSA responses. The data suggest that DSA reduction may be associated with improved DCGS in both early and late AMR.
Authors: Marius Andreas Koslik; Justa Friebus-Kardash; Falko Markus Heinemann; Andreas Kribben; Jan Hinrich Bräsen; Ute Eisenberger Journal: Front Med (Lausanne) Date: 2022-01-31
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