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 -