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. 2019 Oct;19(10):2926-2933.
doi: 10.1111/ajt.15486. Epub 2019 Jul 1.

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

Sebastiaan Heidt  1 , Geert W Haasnoot  1 , Marian D Witvliet  1 , Marissa J H van der Linden-van Oevelen  1 , Elena G Kamburova  2 , Bram W Wisse  2 , 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  5 , Arjan D van Zuilen  5 , Marianne C Verhaar  5 , Michiel L Bots  6 , Adriaan C A D Drop  2 , Loes Plaisier  2 , Marc A J Seelen  7 , Jan-Stephan Sanders  7 , Bouke G Hepkema  8 , Annechien J A Lambeck  8 , Laura B Bungener  8 , Caroline Roozendaal  8 , Marcel G J Tilanus  9 , Christina E Voorter  9 , Lotte Wieten  9 , Elly M van Duijnhoven  10 , Marielle A C J Gelens  10 , Maarten H L Christiaans  10 , Frans J van Ittersum  11 , Shaikh A Nurmohamed  11 , Neubury M Lardy  12 , Wendy Swelsen  12 , Karlijn A M I van der Pant  13 , Neelke C van der Weerd  13 , Ineke J M Ten Berge  13 , Frederike J Bemelman  13 , Andries Hoitsma  14 , Paul J M van der Boog  15 , Johan W de Fijter  15 , Michiel G H Betjes  16 , Henny G Otten  2 , Dave L Roelen  17 , Frans H J Claas  1
Affiliations

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients

Sebastiaan Heidt et al. Am J Transplant. 2019 Oct.

Abstract

Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals.

Keywords: alloantibody; clinical research/practice; histocompatibility; immunogenetics; kidney transplantation/nephrology; major histocompatibility complex (MHC); rejection.

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Figures

Figure 1
Figure 1
A, Comparison of 6‐month cumulative rejection incidence between patients transplanted through the acceptable mismatch (AM) program or through the Eurotransplant Kidney Allocation System (ETKAS). B, Comparison of 5‐year cumulative rejection incidence between patients transplanted through the AM program or through ETKAS, for which rejection incidence was set at zero on 6 months. The ETKAS patients are subdivided based on their sensitization grade: 0% to 5% peak PRA: nonsensitized; 6% to 85% peak PRA: intermediately sensitized; and >85% peak PRA: highly sensitized. P value calculated with log‐rank test and corrected for multiple comparisons (Bonferroni method)
Figure 2
Figure 2
Minimal match criteria do not affect rejection rates for patients transplanted through the Acceptable Mismatch (AM) program. A, The 6‐month cumulative rejection incidence of highly sensitized patients transplanted through the Eurotransplant Kidney Allocation System (ETKAS) with a minimal match level of 1 HLA‐B and 1 HLA‐DR antigen, or 2 HLA‐DR antigens on the split antigen level (equivalent to minimal match criteria), or transplanted with 1 HLA‐DR match at the broad antigen level. B, The 6‐month cumulative rejection incidence of AM patients transplanted according to the minimal match criteria of 1 HLA‐B and 1 HLA‐DR antigen, or 2 HLA‐DR antigens on the split antigen level, or transplanted 1 HLA‐DR match at the broad antigen level
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References

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