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, Mariëlle 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

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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 languageEnglish
Pages (from-to)1056-1063
Number of pages8
JournalNephrology, Dialysis, Transplantation
Volume34
Issue number6
DOIs
Publication statusPublished - Jun-2019

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