A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival

Laura A. Michielsen; Bram W. Wisse; Elena G. Kamburova; Marianne C. Verhaar; Irma Joosten; Wil A. Allebes; Arnold van der Meer; Luuk B. Hilbrands; Marije C. Baas; Eric Spierings; Cornelis E. Hack; Franka E. van Reekum; Michiel L. Bots; Adriaan C. A. D. Drop; Loes Plaisier; Marc A. J. Seelen; Jan-Stephan F. Sanders; Bouke G. Hepkema; Annechien J. Lambeck; Laura B. Bungener; Caroline Roozendaal; Marcel G. J. Tilanus; Christien E. Voorter; Lotte Wieten; Elizabeth M. van Duijnhoven; Marielle Gelens; Maarten H. L. Christiaans; Frans J. van Ittersum; Shaikh A. Nurmohamed; Neubury M. Lardy; Wendy Swelsen; Karlijn A. 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; Sebastiaan Heidt; Dave L. Roelen; Frans H. Claas; Henderikus G. Otten; Arjan D. van Zuilen

doi:10.1093/ndt/gfy316

A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival

Laura A. Michielsen^*, Bram W. Wisse, Elena G. Kamburova, Marianne C. Verhaar, Irma Joosten, Wil A. Allebes, Arnold van der Meer, Luuk B. Hilbrands, Marije C. Baas, Eric Spierings, Cornelis E. Hack, Franka E. van Reekum, Michiel L. Bots, Adriaan C. A. D. Drop, Loes Plaisier, Marc A. J. Seelen, Jan-Stephan F. Sanders, Bouke G. Hepkema, Annechien J. Lambeck, Laura B. BungenerCaroline Roozendaal, Marcel G. J. Tilanus, Christien E. Voorter, Lotte Wieten, Elizabeth M. van Duijnhoven, Marielle Gelens, Maarten H. L. Christiaans, Frans J. van Ittersum, Shaikh A. Nurmohamed, Neubury M. Lardy, Wendy Swelsen, Karlijn A. 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, Sebastiaan Heidt, Dave L. Roelen, Frans H. Claas, Henderikus G. Otten, Arjan D. van Zuilen

^*Corresponding author for this work

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

Abstract

Background Pre-transplant donor-specific anti-human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA antibodies (nDSAs) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSAs and nDSAs.

Methods To eliminate donor and era-dependent factors, a post hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995 and 2005 with available pre-transplant serum samples. Anti-HLA antibodies were detected with a Luminex single-antigen bead assay.

Results Among 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies. Patients with pre-transplant DSAs had a significantly lower 10-year death-censored graft survival (55% versus 82%, P=0.0001). We identified 192 pairs with one recipient as nDSA positive (against Class I and/or II) and the other without anti-HLA antibodies. For the patients with nDSAs against either Class I or II, graft survival did not significantly differ compared with patients without anti-HLA antibodies (74% versus 77%, P=0.79). Only in patients with both nDSAs Class I and II was there a trend towards a lower graft survival (58%, P=0.06). Lastly, in a small group of 42 recipient pairs, 10-year graft survival in recipients with DSAs was 49% compared with 68% in recipients with nDSAs (P=0.11).

Conclusion This paired kidney analysis confirms that the presence of pre-transplant DSAs in deceased donor transplantations is a risk marker for graft loss, whereas nDSAs in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSAs against Class I and II, nDSAs may be a risk marker for graft loss in the long term.

Original language	English
Pages (from-to)	1056-1063
Number of pages	8
Journal	Nephrology Dialysis Transplantation
Volume	34
Issue number	6
DOIs	https://doi.org/10.1093/ndt/gfy316
Publication status	Published - Jun 2019

Keywords

acute rejection
graft survival
HLA antibodies
immunology
kidney transplantation
DONOR-SPECIFIC ANTIBODIES
HUMAN-LEUKOCYTE ANTIGEN
DP-SPECIFIC ANTIBODIES
MEDIATED REJECTION
CLINICAL-RELEVANCE
RISK-FACTOR
BEAD ASSAY
LOSS EVEN
RECIPIENTS
INDUCTION

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10.1093/ndt/gfy316

Cite this

Michielsen, L. A., Wisse, B. W., Kamburova, E. G., Verhaar, M. C., Joosten, I., Allebes, W. A., van der Meer, A., Hilbrands, L. B., Baas, M. C., Spierings, E., Hack, C. E., van Reekum, F. E., Bots, M. L., Drop, A. C. A. D., Plaisier, L., Seelen, M. A. J., Sanders, J.-S. F., Hepkema, B. G., Lambeck, A. J., ... van Zuilen, A. D. (2019). A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival. Nephrology Dialysis Transplantation, 34(6), 1056-1063. https://doi.org/10.1093/ndt/gfy316

@article{9d8b065e24644095a5036b2af8e6c874,

title = "A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival",

abstract = "Background Pre-transplant donor-specific anti-human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA antibodies (nDSAs) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSAs and nDSAs.Methods To eliminate donor and era-dependent factors, a post hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995 and 2005 with available pre-transplant serum samples. Anti-HLA antibodies were detected with a Luminex single-antigen bead assay.Results Among 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies. Patients with pre-transplant DSAs had a significantly lower 10-year death-censored graft survival (55% versus 82%, P=0.0001). We identified 192 pairs with one recipient as nDSA positive (against Class I and/or II) and the other without anti-HLA antibodies. For the patients with nDSAs against either Class I or II, graft survival did not significantly differ compared with patients without anti-HLA antibodies (74% versus 77%, P=0.79). Only in patients with both nDSAs Class I and II was there a trend towards a lower graft survival (58%, P=0.06). Lastly, in a small group of 42 recipient pairs, 10-year graft survival in recipients with DSAs was 49% compared with 68% in recipients with nDSAs (P=0.11).Conclusion This paired kidney analysis confirms that the presence of pre-transplant DSAs in deceased donor transplantations is a risk marker for graft loss, whereas nDSAs in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSAs against Class I and II, nDSAs may be a risk marker for graft loss in the long term.",

keywords = "acute rejection, graft survival, HLA antibodies, immunology, kidney transplantation, DONOR-SPECIFIC ANTIBODIES, HUMAN-LEUKOCYTE ANTIGEN, DP-SPECIFIC ANTIBODIES, MEDIATED REJECTION, CLINICAL-RELEVANCE, RISK-FACTOR, BEAD ASSAY, LOSS EVEN, RECIPIENTS, INDUCTION",

author = "Michielsen, {Laura A.} and Wisse, {Bram W.} and Kamburova, {Elena G.} and Verhaar, {Marianne C.} 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 Bots, {Michiel L.} and Drop, {Adriaan C. A. D.} and Loes Plaisier and Seelen, {Marc A. J.} and Sanders, {Jan-Stephan F.} and Hepkema, {Bouke G.} and Lambeck, {Annechien J.} and Bungener, {Laura B.} and Caroline Roozendaal and Tilanus, {Marcel G. J.} and Voorter, {Christien E.} and Lotte Wieten and {van Duijnhoven}, {Elizabeth M.} and Marielle Gelens 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.} 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 Sebastiaan Heidt and Roelen, {Dave L.} and Claas, {Frans H.} and Otten, {Henderikus G.} and {van Zuilen}, {Arjan D.}",

note = "Funding Information: This study was supported by research funding from the Dutch Kidney Foundation Project (CP12.23). Funding Information: L.A.M. is supported by an unrestricted research grant from Astellas Pharma. E.S. is listed as the inventor of a patent unrelated to this article. A.D.v.Z. received personal fees from Astellas Pharma, Novartis and Chiesi outside the scope of this article. None of the other authors have any conflicts of interest to disclose. Publisher Copyright: {\textcopyright} The Author(s) 2018.",

year = "2019",

month = jun,

doi = "10.1093/ndt/gfy316",

language = "English",

volume = "34",

pages = "1056--1063",

journal = "Nephrology Dialysis Transplantation",

issn = "0931-0509",

publisher = "Oxford University Press",

number = "6",

}

Michielsen, LA, Wisse, BW, Kamburova, EG, Verhaar, MC, Joosten, I, Allebes, WA, van der Meer, A, Hilbrands, LB, Baas, MC, Spierings, E, Hack, CE, van Reekum, FE, Bots, ML, Drop, ACAD, Plaisier, L, Seelen, MAJ, Sanders, J-SF, Hepkema, BG, Lambeck, AJ, Bungener, LB, Roozendaal, C, Tilanus, MGJ, Voorter, CE , Wieten, L, van Duijnhoven, EM, Gelens, M , Christiaans, MHL, van Ittersum, FJ, Nurmohamed, SA, Lardy, NM, Swelsen, W, van der Pant, KA, van der Weerd, NC, ten Berge, IJM, Bemelman, FJ, Hoitsma, A, van der Boog, PJM, de Fijter, JW, Betjes, MGH, Heidt, S, Roelen, DL, Claas, FH, Otten, HG & van Zuilen, AD 2019, 'A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival', Nephrology Dialysis Transplantation, vol. 34, no. 6, pp. 1056-1063. https://doi.org/10.1093/ndt/gfy316

TY - JOUR

T1 - A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival

AU - Michielsen, Laura A.

AU - Wisse, Bram W.

AU - Kamburova, Elena G.

AU - Verhaar, Marianne C.

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 - Bots, Michiel L.

AU - Drop, Adriaan C. A. D.

AU - Plaisier, Loes

AU - Seelen, Marc A. J.

AU - Sanders, Jan-Stephan F.

AU - Hepkema, Bouke G.

AU - Lambeck, Annechien J.

AU - Bungener, Laura B.

AU - Roozendaal, Caroline

AU - Tilanus, Marcel G. J.

AU - Voorter, Christien E.

AU - Wieten, Lotte

AU - van Duijnhoven, Elizabeth M.

AU - Gelens, Marielle

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.

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 - Heidt, Sebastiaan

AU - Roelen, Dave L.

AU - Claas, Frans H.

AU - Otten, Henderikus G.

AU - van Zuilen, Arjan D.

N1 - Funding Information: This study was supported by research funding from the Dutch Kidney Foundation Project (CP12.23). Funding Information: L.A.M. is supported by an unrestricted research grant from Astellas Pharma. E.S. is listed as the inventor of a patent unrelated to this article. A.D.v.Z. received personal fees from Astellas Pharma, Novartis and Chiesi outside the scope of this article. None of the other authors have any conflicts of interest to disclose. Publisher Copyright: © The Author(s) 2018.

PY - 2019/6

Y1 - 2019/6

N2 - Background Pre-transplant donor-specific anti-human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA antibodies (nDSAs) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSAs and nDSAs.Methods To eliminate donor and era-dependent factors, a post hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995 and 2005 with available pre-transplant serum samples. Anti-HLA antibodies were detected with a Luminex single-antigen bead assay.Results Among 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies. Patients with pre-transplant DSAs had a significantly lower 10-year death-censored graft survival (55% versus 82%, P=0.0001). We identified 192 pairs with one recipient as nDSA positive (against Class I and/or II) and the other without anti-HLA antibodies. For the patients with nDSAs against either Class I or II, graft survival did not significantly differ compared with patients without anti-HLA antibodies (74% versus 77%, P=0.79). Only in patients with both nDSAs Class I and II was there a trend towards a lower graft survival (58%, P=0.06). Lastly, in a small group of 42 recipient pairs, 10-year graft survival in recipients with DSAs was 49% compared with 68% in recipients with nDSAs (P=0.11).Conclusion This paired kidney analysis confirms that the presence of pre-transplant DSAs in deceased donor transplantations is a risk marker for graft loss, whereas nDSAs in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSAs against Class I and II, nDSAs may be a risk marker for graft loss in the long term.

AB - Background Pre-transplant donor-specific anti-human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA antibodies (nDSAs) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSAs and nDSAs.Methods To eliminate donor and era-dependent factors, a post hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995 and 2005 with available pre-transplant serum samples. Anti-HLA antibodies were detected with a Luminex single-antigen bead assay.Results Among 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies. Patients with pre-transplant DSAs had a significantly lower 10-year death-censored graft survival (55% versus 82%, P=0.0001). We identified 192 pairs with one recipient as nDSA positive (against Class I and/or II) and the other without anti-HLA antibodies. For the patients with nDSAs against either Class I or II, graft survival did not significantly differ compared with patients without anti-HLA antibodies (74% versus 77%, P=0.79). Only in patients with both nDSAs Class I and II was there a trend towards a lower graft survival (58%, P=0.06). Lastly, in a small group of 42 recipient pairs, 10-year graft survival in recipients with DSAs was 49% compared with 68% in recipients with nDSAs (P=0.11).Conclusion This paired kidney analysis confirms that the presence of pre-transplant DSAs in deceased donor transplantations is a risk marker for graft loss, whereas nDSAs in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSAs against Class I and II, nDSAs may be a risk marker for graft loss in the long term.

KW - acute rejection

KW - graft survival

KW - HLA antibodies

KW - immunology

KW - kidney transplantation

KW - DONOR-SPECIFIC ANTIBODIES

KW - HUMAN-LEUKOCYTE ANTIGEN

KW - DP-SPECIFIC ANTIBODIES

KW - MEDIATED REJECTION

KW - CLINICAL-RELEVANCE

KW - RISK-FACTOR

KW - BEAD ASSAY

KW - LOSS EVEN

KW - RECIPIENTS

KW - INDUCTION

U2 - 10.1093/ndt/gfy316

DO - 10.1093/ndt/gfy316

M3 - Article

C2 - 30365008

SN - 0931-0509

VL - 34

SP - 1056

EP - 1063

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

IS - 6

ER -