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

Publication date

2019-06-01

Authors

Michielsen, Laura A
Wisse, Bram W.ISNI 0000000396383562
Kamburova, E. G.
Verhaar, Marianne C.ORCID 0000-0002-3276-6428ISNI 0000000390259392
Joosten, Irma
Allebes, Wil A
van der Meer, Arnold
Hilbrands, Luuk B
Baas, Marije C
Spierings, EricORCID 0000-0001-9441-1019ISNI 0000000391074963

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Document Type

Article

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taverne

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

Journal Article, Acute rejection, Graft survival, Immunology, HLA antibodies, Kidney transplantation, acute rejection, kidney transplantation, graft survival, immunology, Taverne, Nephrology, Transplantation

Citation

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, 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, Bungener, L B, Roozendaal, C, Tilanus, M G J, Voorter, C E, Wieten, L, van Duijnhoven, E M, Gelens, M, Christiaans, M H L, van Ittersum, F J, Nurmohamed, S A, Lardy, N M, Swelsen, W, van der Pant, K A, van der Weerd, N C, Ten Berge, I J M, Bemelman, F J, Hoitsma, A, van der Boog, P J M, de Fijter, J W, Betjes, M G H, Heidt, S, Roelen, D L, Claas, F H, Otten, H G & van Zuilen, A D 2019, 'A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival', Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, vol. 34, no. 6, pp. 1056-1063. https://doi.org/10.1093/ndt/gfy316