Elisabeth Schwaiger1, Farsad Eskandary2, Nicolas Kozakowski3, Gregor Bond1, Željko Kikić1, Daniel Yoo4, Susanne Rasoul-Rockenschaub5, Rainer Oberbauer1, Georg A Böhmig1. 1. Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria. 2. Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria Alberta Transplant Applied Genomics Centre, ATAGC, University of Alberta, Edmonton, AB, Canada. 3. Department of Clinical Pathology, Medical University Vienna, Vienna, Austria. 4. Transcriptome Sciences Inc., 250 Heritage Medical Research Centre, University of Alberta, Edmonton, AB, Canada. 5. Center for Medical Statistics, Informatics and Intelligent Systems, Medical University Vienna, Vienna, Austria.
Abstract
BACKGROUND: Apheresis-based desensitization allows for successful transplantation across major immunological barriers. For donor-specific antibody (DSA)- and/or crossmatch-positive transplantation, however, it has been shown that even intense immunomodulation may not completely prevent antibody-mediated rejection (ABMR). METHODS: In this study, we evaluated transplant outcomes in 101 DSA+ deceased donor kidney transplant recipients (transplantation between 2009 and 2013; median follow-up: 24 months) who were subjected to immunoadsorption (IA)-based desensitization. Treatment included a single pre-transplant IA session, followed by anti-lymphocyte antibody and serial post-transplant IA. In 27 cases, a positive complement-dependent cytotoxicity crossmatch (CDCXM) was rendered negative immediately before transplantation. Seventy-four of the DSA+ recipients had a negative CDCXM already before IA. RESULTS: Three-year death-censored graft survival in DSA+ patients was significantly worse than in 513 DSA- recipients transplanted during the same period (79 versus 88%, P = 0.008). Thirty-three DSA+ recipients (33%) had ABMR. While a positive baseline CDCXM showed only a trend towards higher ABMR rates (41 versus 30% in CDCXM- recipients, P = 0.2), DSA mean fluorescence intensity (MFI) in single bead assays significantly associated with rejection, showing 20 versus 71% ABMR rates at <5000 versus >15 000 peak DSA MFI. The predictive value of MFI was moderate, with the highest accuracy at a median of 13 300 MFI (after cross-validation: 0.72). Other baseline variables, including CDC assay results, human leukocyte antigen mismatch, prior transplantation or type of induction treatment, did not add independent predictive information. CONCLUSIONS: IA-based desensitization failed to prevent ABMR in a considerable number of DSA+ recipients. Assessing DSA MFI may help stratify risk of rejection, supporting its use as a guide to organ allocation and individualized treatment.
BACKGROUND: Apheresis-based desensitization allows for successful transplantation across major immunological barriers. For donor-specific antibody (DSA)- and/or crossmatch-positive transplantation, however, it has been shown that even intense immunomodulation may not completely prevent antibody-mediated rejection (ABMR). METHODS: In this study, we evaluated transplant outcomes in 101 DSA+ deceased donor kidney transplant recipients (transplantation between 2009 and 2013; median follow-up: 24 months) who were subjected to immunoadsorption (IA)-based desensitization. Treatment included a single pre-transplant IA session, followed by anti-lymphocyte antibody and serial post-transplant IA. In 27 cases, a positive complement-dependent cytotoxicity crossmatch (CDCXM) was rendered negative immediately before transplantation. Seventy-four of the DSA+ recipients had a negative CDCXM already before IA. RESULTS: Three-year death-censored graft survival in DSA+patients was significantly worse than in 513 DSA- recipients transplanted during the same period (79 versus 88%, P = 0.008). Thirty-three DSA+ recipients (33%) had ABMR. While a positive baseline CDCXM showed only a trend towards higher ABMR rates (41 versus 30% in CDCXM- recipients, P = 0.2), DSA mean fluorescence intensity (MFI) in single bead assays significantly associated with rejection, showing 20 versus 71% ABMR rates at <5000 versus >15 000 peak DSA MFI. The predictive value of MFI was moderate, with the highest accuracy at a median of 13 300 MFI (after cross-validation: 0.72). Other baseline variables, including CDC assay results, human leukocyte antigen mismatch, prior transplantation or type of induction treatment, did not add independent predictive information. CONCLUSIONS: IA-based desensitization failed to prevent ABMR in a considerable number of DSA+ recipients. Assessing DSA MFI may help stratify risk of rejection, supporting its use as a guide to organ allocation and individualized treatment.
Authors: Farsad Eskandary; Heinz Regele; Lukas Baumann; Gregor Bond; Nicolas Kozakowski; Markus Wahrmann; Luis G Hidalgo; Helmuth Haslacher; Christopher C Kaltenecker; Marie-Bernadette Aretin; Rainer Oberbauer; Martin Posch; Anton Staudenherz; Ammon Handisurya; Jeff Reeve; Philip F Halloran; Georg A Böhmig Journal: J Am Soc Nephrol Date: 2017-12-14 Impact factor: 10.121
Authors: Kyle R Jackson; Karina Covarrubias; Courtenay M Holscher; Xun Luo; Jennifer Chen; Allan B Massie; Niraj Desai; Daniel C Brennan; Dorry L Segev; Jacqueline Garonzik-Wang Journal: Am J Transplant Date: 2018-11-26 Impact factor: 8.086
Authors: Konstantin Doberer; Michael Duerr; Philip F Halloran; Farsad Eskandary; Klemens Budde; Heinz Regele; Jeff Reeve; Anita Borski; Nicolas Kozakowski; Roman Reindl-Schwaighofer; Johannes Waiser; Nils Lachmann; Sabine Schranz; Christa Firbas; Jakob Mühlbacher; Georg Gelbenegger; Thomas Perkmann; Markus Wahrmann; Alexander Kainz; Robin Ristl; Fabian Halleck; Gregor Bond; Edward Chong; Bernd Jilma; Georg A Böhmig Journal: J Am Soc Nephrol Date: 2020-12-18 Impact factor: 10.121
Authors: Mostafa T Mohammed; Songjie Cai; Benjamin L Hanson; Hengcheng Zhang; Rachel L Clement; Joe Daccache; Cecilia B Cavazzoni; Bruce R Blazar; Alessandro Alessandrini; Helmut G Rennke; Anil Chandraker; Peter T Sage Journal: Am J Transplant Date: 2021-02-11 Impact factor: 9.369
Authors: Jakob Mühlbacher; Bernd Jilma; Markus Wahrmann; Johann Bartko; Farsad Eskandary; Christian Schörgenhofer; Michael Schwameis; Graham C Parry; James C Gilbert; Sandip Panicker; Georg A Böhmig Journal: Transplantation Date: 2017-10 Impact factor: 4.939
Authors: Martin Schiemann; Elisabeth Puchhammer-Stöckl; Farsad Eskandary; Philip Kohlbeck; Susanne Rasoul-Rockenschaub; Andreas Heilos; Nicolas Kozakowski; Irene Görzer; Željko Kikić; Harald Herkner; Georg A Böhmig; Gregor Bond Journal: Transplantation Date: 2017-02 Impact factor: 4.939
Authors: Mohammadreza Nemati; Haonan Zhang; Michael Sloma; Dulat Bekbolsynov; Hong Wang; Stanislaw Stepkowski; Kevin S Xu Journal: Artif Intell Med Conf Artif Intell Med (2005-) Date: 2021-06-08