Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

Sebastiaan Heidt; Geert W. Haasnoot; Marian D. Witvliet; Marissa J. H. van der Linden-van Oevelen; Elena G. Kamburova; Bram W. Wisse; Irma Joosten; Wil A. Allebes; Arnold van der Meer; Luuk B. Hilbrands; Marije C. Baas; Eric Spierings; Cornelis E. Hack; Franka E. van Reekum; Arjan D. van Zuilen; Marianne C. Verhaar; Michiel L. Bots; Adriaan C. A. D. Drop; Loes Plaisier; Marc A. J. Seelen; Jan-Stephan Sanders; Bouke G. Hepkema; Annechien J. A. Lambeck; Laura B. Bungener; Caroline Roozendaal; Marcel G. J. Tilanus; Christina E. Voorter; Lotte Wieten; Elly M. van Duijnhoven; Marielle A. C. J. Gelens; Maarten H. L. Christiaans; Frans J. van Ittersum; Shaikh A. Nurmohamed; Neubury M. Lardy; Wendy Swelsen; Karlijn A. M. I. van der Pant; Neelke C. van der Weerd; Ineke J. M. ten Berge; Frederike J. Bemelman; Andries Hoitsma; Paul J. M. van der Boog; Johan W. de Fijter; Michiel G. H. Betjes; Henny G. Otten; Dave L. Roelen; Frans H. J. Claas

doi:10.1111/ajt.15486

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

Sebastiaan Heidt^*, Geert W. Haasnoot, Marian D. Witvliet, Marissa J. H. van der Linden-van Oevelen, Elena G. Kamburova, Bram W. Wisse, Irma Joosten, Wil A. Allebes, Arnold van der Meer, Luuk B. Hilbrands, Marije C. Baas, Eric Spierings, Cornelis E. Hack, Franka E. van Reekum, Arjan D. van Zuilen, Marianne C. Verhaar, Michiel L. Bots, Adriaan C. A. D. Drop, Loes Plaisier, Marc A. J. SeelenJan-Stephan Sanders, Bouke G. Hepkema, Annechien J. A. Lambeck, Laura B. Bungener, Caroline Roozendaal, Marcel G. J. Tilanus, Christina E. Voorter, Lotte Wieten, Elly M. van Duijnhoven, Marielle A. C. J. Gelens, Maarten H. L. Christiaans, Frans J. van Ittersum, Shaikh A. Nurmohamed, Neubury M. Lardy, Wendy Swelsen, Karlijn A. M. I. van der Pant, Neelke C. van der Weerd, Ineke J. M. ten Berge, Frederike J. Bemelman, Andries Hoitsma, Paul J. M. van der Boog, Johan W. de Fijter, Michiel G. H. Betjes, Henny G. Otten, Dave L. Roelen, Frans H. J. Claas

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals.

Original language	English
Pages (from-to)	2926-2933
Number of pages	8
Journal	American Journal of Transplantation
Volume	19
Issue number	10
DOIs	https://doi.org/10.1111/ajt.15486
Publication status	Published - Oct 2019

Keywords

alloantibody
clinical research
practice
histocompatibility
immunogenetics
kidney transplantation
nephrology
major histocompatibility complex (MHC)
rejection
DONOR-SPECIFIC ANTIBODIES
MATERNAL HLA ANTIGENS
CLINICAL-RELEVANCE
KIDNEY ALLOCATION
RISK
TRANSPLANTATION
SURVIVAL
PROGRAM

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10.1111/ajt.15486Licence: CC BY-NC

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Heidt, S., Haasnoot, G. W., Witvliet, M. D., van der Linden-van Oevelen, M. J. H., Kamburova, E. G., Wisse, B. W., Joosten, I., Allebes, W. A., van der Meer, A., Hilbrands, L. B., Baas, M. C., Spierings, E., Hack, C. E., van Reekum, F. E., van Zuilen, A. D., Verhaar, M. C., Bots, M. L., Drop, A. C. A. D., Plaisier, L., ... Claas, F. H. J. (2019). Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients. American Journal of Transplantation, 19(10), 2926-2933. https://doi.org/10.1111/ajt.15486

@article{e18199843a4c4278969cb33b2c73bd96,

title = "Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients",

abstract = "Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals.",

keywords = "alloantibody, clinical research, practice, histocompatibility, immunogenetics, kidney transplantation, nephrology, major histocompatibility complex (MHC), rejection, DONOR-SPECIFIC ANTIBODIES, MATERNAL HLA ANTIGENS, CLINICAL-RELEVANCE, KIDNEY ALLOCATION, RISK, TRANSPLANTATION, SURVIVAL, PROGRAM",

author = "Sebastiaan Heidt and Haasnoot, {Geert W.} and Witvliet, {Marian D.} and {van der Linden-van Oevelen}, {Marissa J. H.} and Kamburova, {Elena G.} and Wisse, {Bram W.} and Irma Joosten and Allebes, {Wil A.} and {van der Meer}, Arnold and Hilbrands, {Luuk B.} and Baas, {Marije C.} and Eric Spierings and Hack, {Cornelis E.} and {van Reekum}, {Franka E.} and {van Zuilen}, {Arjan D.} and Verhaar, {Marianne C.} and Bots, {Michiel L.} and Drop, {Adriaan C. A. D.} and Loes Plaisier and Seelen, {Marc A. J.} and Jan-Stephan Sanders and Hepkema, {Bouke G.} and Lambeck, {Annechien J. A.} and Bungener, {Laura B.} and Caroline Roozendaal and Tilanus, {Marcel G. J.} and Voorter, {Christina E.} and Lotte Wieten and {van Duijnhoven}, {Elly M.} and Gelens, {Marielle A. C. J.} and Christiaans, {Maarten H. L.} and {van Ittersum}, {Frans J.} and Nurmohamed, {Shaikh A.} and Lardy, {Neubury M.} and Wendy Swelsen and {van der Pant}, {Karlijn A. M. I.} and {van der Weerd}, {Neelke C.} and {ten Berge}, {Ineke J. M.} and Bemelman, {Frederike J.} and Andries Hoitsma and {van der Boog}, {Paul J. M.} and {de Fijter}, {Johan W.} and Betjes, {Michiel G. H.} and Otten, {Henny G.} and Roelen, {Dave L.} and Claas, {Frans H. J.}",

note = "Funding Information: The PROCARE study was supported by research funding from Dutch Kidney Foundation project code CP12.23 (risk assessment of kidney graft failure by HLA antibody profiling). The authors thank the Eurotransplant staff and all Eurotransplant HLA laboratories and transplantation centers for their constructive collaboration and participation in the AM program. Publisher Copyright: {\textcopyright} 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.",

year = "2019",

month = oct,

doi = "10.1111/ajt.15486",

language = "English",

volume = "19",

pages = "2926--2933",

journal = "American Journal of Transplantation",

issn = "1600-6135",

publisher = "Wiley",

number = "10",

}

Heidt, S, Haasnoot, GW, Witvliet, MD, van der Linden-van Oevelen, MJH, Kamburova, EG, Wisse, BW, Joosten, I, Allebes, WA, van der Meer, A, Hilbrands, LB, Baas, MC, Spierings, E, Hack, CE, van Reekum, FE, van Zuilen, AD, Verhaar, MC, Bots, ML, Drop, ACAD, Plaisier, L, Seelen, MAJ, Sanders, J-S, Hepkema, BG, Lambeck, AJA, Bungener, LB, Roozendaal, C, Tilanus, MGJ, Voorter, CE , Wieten, L , van Duijnhoven, EM , Gelens, MACJ , Christiaans, MHL, van Ittersum, FJ, Nurmohamed, SA, Lardy, NM, Swelsen, W, van der Pant, KAMI, van der Weerd, NC, ten Berge, IJM, Bemelman, FJ, Hoitsma, A, van der Boog, PJM, de Fijter, JW, Betjes, MGH, Otten, HG, Roelen, DL & Claas, FHJ 2019, 'Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients', American Journal of Transplantation, vol. 19, no. 10, pp. 2926-2933. https://doi.org/10.1111/ajt.15486

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients. / Heidt, Sebastiaan; Haasnoot, Geert W.; Witvliet, Marian D. et al.
In: American Journal of Transplantation, Vol. 19, No. 10, 10.2019, p. 2926-2933.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

AU - Heidt, Sebastiaan

AU - Haasnoot, Geert W.

AU - Witvliet, Marian D.

AU - van der Linden-van Oevelen, Marissa J. H.

AU - Kamburova, Elena G.

AU - Wisse, Bram W.

AU - Joosten, Irma

AU - Allebes, Wil A.

AU - van der Meer, Arnold

AU - Hilbrands, Luuk B.

AU - Baas, Marije C.

AU - Spierings, Eric

AU - Hack, Cornelis E.

AU - van Reekum, Franka E.

AU - van Zuilen, Arjan D.

AU - Verhaar, Marianne C.

AU - Bots, Michiel L.

AU - Drop, Adriaan C. A. D.

AU - Plaisier, Loes

AU - Seelen, Marc A. J.

AU - Sanders, Jan-Stephan

AU - Hepkema, Bouke G.

AU - Lambeck, Annechien J. A.

AU - Bungener, Laura B.

AU - Roozendaal, Caroline

AU - Tilanus, Marcel G. J.

AU - Voorter, Christina E.

AU - Wieten, Lotte

AU - van Duijnhoven, Elly M.

AU - Gelens, Marielle A. C. J.

AU - Christiaans, Maarten H. L.

AU - van Ittersum, Frans J.

AU - Nurmohamed, Shaikh A.

AU - Lardy, Neubury M.

AU - Swelsen, Wendy

AU - van der Pant, Karlijn A. M. I.

AU - van der Weerd, Neelke C.

AU - ten Berge, Ineke J. M.

AU - Bemelman, Frederike J.

AU - Hoitsma, Andries

AU - van der Boog, Paul J. M.

AU - de Fijter, Johan W.

AU - Betjes, Michiel G. H.

AU - Otten, Henny G.

AU - Roelen, Dave L.

AU - Claas, Frans H. J.

N1 - Funding Information: The PROCARE study was supported by research funding from Dutch Kidney Foundation project code CP12.23 (risk assessment of kidney graft failure by HLA antibody profiling). The authors thank the Eurotransplant staff and all Eurotransplant HLA laboratories and transplantation centers for their constructive collaboration and participation in the AM program. Publisher Copyright: © 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.

PY - 2019/10

Y1 - 2019/10

N2 - Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals.

AB - Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals.

KW - alloantibody

KW - clinical research

KW - practice

KW - histocompatibility

KW - immunogenetics

KW - kidney transplantation

KW - nephrology

KW - major histocompatibility complex (MHC)

KW - rejection

KW - DONOR-SPECIFIC ANTIBODIES

KW - MATERNAL HLA ANTIGENS

KW - CLINICAL-RELEVANCE

KW - KIDNEY ALLOCATION

KW - RISK

KW - TRANSPLANTATION

KW - SURVIVAL

KW - PROGRAM

U2 - 10.1111/ajt.15486

DO - 10.1111/ajt.15486

M3 - Article

C2 - 31155833

SN - 1600-6135

VL - 19

SP - 2926

EP - 2933

JO - American Journal of Transplantation

JF - American Journal of Transplantation

IS - 10

ER -