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Multicenter Study
. 2019 Jun 1;34(6):1056-1063.
doi: 10.1093/ndt/gfy316.

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

Laura A Michielsen  1 , Bram W Wisse  2 , Elena G Kamburova  2 , Marianne C Verhaar  1 , Irma Joosten  3 , Wil A Allebes  3 , Arnold van der Meer  3 , Luuk B Hilbrands  4 , Marije C Baas  4 , Eric Spierings  2 , Cornelis E Hack  2 , Franka E van Reekum  1 , Michiel L Bots  5 , Adriaan C A D Drop  2 , Loes Plaisier  2 , Marc A J Seelen  6 , Jan-Stephan F Sanders  6 , Bouke G Hepkema  7 , Annechien J Lambeck  7 , Laura B Bungener  7 , Caroline Roozendaal  7 , Marcel G J Tilanus  8 , Christien E Voorter  8 , Lotte Wieten  8 , Elizabeth M van Duijnhoven  9 , Mariëlle Gelens  9 , Maarten H L Christiaans  9 , Frans J van Ittersum  10 , Shaikh A Nurmohamed  10 , Neubury M Lardy  11 , Wendy Swelsen  11 , Karlijn A van der Pant  12 , Neelke C van der Weerd  12 , Ineke J M Ten Berge  12 , Frederike J Bemelman  12 , Andries Hoitsma  13 , Paul J M van der Boog  14 , Johan W de Fijter  14 , Michiel G H Betjes  15 , Sebastiaan Heidt  16 , Dave L Roelen  16 , Frans H Claas  16 , Henderikus G Otten  2 , Arjan D van Zuilen  1
Affiliations
Multicenter Study

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

Laura A Michielsen et al. Nephrol Dial Transplant. .

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: HLA antibodies; acute rejection; graft survival; immunology; kidney transplantation.

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