Decreased graft survival of retransplants can largely be explained by increased HLA-immunization

E.G. Kamburova, B.W. Wisse, I. Joosten, W.A. Allebes, A. van der Meer, L.B. Hilbrands, M.C. Baas, E. Spierings, C.E. Hack, F.E. van Reekum, A.D. van Zuilen, M.C. Verhaar, M.L. Bots, A.C.A.D. Drop, L. Plaisier, M.A.J. Seelen, J.S.F. Sanders, B. Hepkema, A.J. Lambeck, L.B. Bungener, C. Roozendaal, M.G.J. Tilanus, C.E.M. Voorter, L. Wieten, E.M. van Duijnhoven, M.A.C.J. Gelens, M.H.L. Christiaans, F.J. van Ittersum, A. Nurmohamed, N.M. Lardy, W. Swelsen, K.A.M.I. van der Pant, N.C. van der Weerd, I.J.M. ten Berge, F.J. Bemelman, A.J. Hoitsma, P.J.M. van der Boog, J.W. de Fijter, M.G.H. Betjes, S. Heidt, D.L. Roelen, F.H.J. Claas, H.G. Otten

Thursday 15 march 2018

15:35 - 15:40h at Willem Burger Foyer

Categories: Clinical, Session (poster)

Parallel session: Poster session 3: Clinical

Many kidney recipients will need more than one kidney transplant during a lifetime. Patients often develop anti-HLA antibodies after losing their graft. We investigated the effect of (donor-specific) HLA antibodies (DSA) in retransplanted patients (re-Tx) versus patients transplanted for the first time (first-Tx) in the Dutch PROCARE Consortium study.

The 10-year graft survival of 3127 first-Tx and 142 re-Tx patients without HLA antibodies is comparable (80% vs 81%). If patients have HLA antibodies that are not donor-specific (NDSA) the 10-year graft survival was lower for the 311 re-Tx compared to 577 first-Tx (first-Tx 76% vs re-Tx 71%). This was also the case for patients with DSA: graft survival pf 69% for first-Tx (n=297) vs 57% for re-Tx (n=270). This effect might be HLA antibody independent, but may also be caused by previous transplants inducing more different HLA antibodies. To investigate whether a higher level of immunization might be driving the graft survival differences in the NDSA and DSA groups we analyzed differences in the percentage panel reactive antibodies (%PRA) at time of transplant (current %PRA) and the historically highest level before transplant (high %PRA) between first-Tx and re-Tx.

We found that both %PRA to be considerably higher in re-Tx if (donor specific) HLA antibodies were detected by single antigen bead (SAB) assays in the pretransplant serum. Especially the relative number of transplantations with a current %PRA equal to 0% (these are transplants for which all of the CDC crossmatches against a panel of donors were negative, yet for which SAB assays did pick up HLA antibodies) is considerably higher in first-Tx. After excluding all transplantations with a current %PRA of 0% we reduced the difference in immunization level between first-Tx and re-Tx and found no remaining difference between graft survival of first-Tx and re-Tx for NDSA positive transplantations, and a greatly reduced difference for DSA positive transplantations. In conclusion, in the investigated cohort the relation between retransplantation and graft survival seems to be predominantly dependent on the presence of pretransplant HLA antibodies (NDSA and DSA).

Therefore, one should consider not including the variable retransplantation in a multivariable model to study the effect of HLA antibodies on long term graft survival, as that will likely mask part of the studied effect.