# Impaired graft survival in kidney transplants from expanded criteria donors with HLA-DR mismatch

**Authors:** Uwe Scheuermann, Philipp Rhode, Claudia Lehmann, Jan Kowald, Sophie Seiffer, Fabian Haak, Daniel Seehofer, Sebastian Murad Rabe, Hans-Michael Tautenhahn

PMC · DOI: 10.3389/frtra.2026.1733351 · Frontiers in Transplantation · 2026-02-12

## TL;DR

This study shows that HLA-DR mismatches in kidney transplants from lower-quality donors significantly reduce graft survival and increase rejection risk.

## Contribution

The study identifies HLA-DR mismatch as an independent predictor of graft rejection and reduced survival in expanded criteria donor kidney transplants.

## Key findings

- ECD-DR+ kidney transplants had significantly lower rejection-free graft survival (P = 0.005).
- HLA-DR mismatch was an independent predictor of graft rejection and reduced survival in ECD transplants.
- Graft survival was shorter in ECD-DR+ transplants compared to ECD-DR- transplants (15.1 vs. 10.7 years).

## Abstract

Human leukocyte antigen (HLA)-DR mismatches are known to increase the risk of graft rejection following kidney transplantation (KT). Especially in KT using grafts of lower quality from expanded criteria donors (ECD), the immune response plays a critical role. Therefore, the aim of this study was to investigate the impact of HLA-DR mismatches on both short- and long-term outcomes in primary ECD KT. 537 KT recipients were stratified into four groups based on their HLA-DR mismatch status [absent (−) or present (+)] and donor type [standard criteria donor (SCD) or ECD]: (1) SCD-DR-(N = 126), (2) SCD-DR+ (N = 167), (3) ECD-DR- (N = 60) and (4) ECD-DR+ (N = 184). Clinicopathological characteristics, transplant outcomes and survival were evaluated across the groups. Rejection-free graft survival was significantly decreased in recipients of ECD-DR + KT (P = 0.005). In comparison with ECD-DR- KTs, ECD-DR + KTs were associated with a significantly reduced graft survival (15.1 vs. 10.7 years; P = 0.034). After adjusting for relevant cofactors using multivariate Cox regression analysis, HLA-DR mismatch remained an independent predictor of graft rejection and graft survival in ECD kidney grafts. These results suggest that HLA-DR compatibility should be considered in allocation protocols for this donor category to improve long-term outcomes.

## Full-text entities

- **Genes:** HLA-DRB1 (major histocompatibility complex, class II, DR beta 1) [NCBI Gene 3123] {aka DRB1, HLA-DR1B, HLA-DRB, SS1}, HLA-A (major histocompatibility complex, class I, A) [NCBI Gene 3105] {aka HLAA}, ECD (ecdysoneless cell cycle regulator) [NCBI Gene 11319] {aka GCR2, HSGT1, SGT1}, IL2RA (interleukin 2 receptor subunit alpha) [NCBI Gene 3559] {aka CD25, IDDM10, IL2R, IMD41, TCGFR, p55}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, IL2RB (interleukin 2 receptor subunit beta) [NCBI Gene 3560] {aka CD122, IL15RB, IMD63, P70-75}, SCD (stearoyl-CoA desaturase) [NCBI Gene 6319] {aka FADS5, MSTP008, SCD1, SCDOS, hSCD1}
- **Diseases:** CVA (MESH:D020521), CMV (MESH:D003586), heart failure (MESH:D006333), sepsis (MESH:D018805), septic shock (MESH:D012772), H (MESH:D000848), pulmonary embolism (MESH:D011655), proteinuria (MESH:D011507), Death (MESH:D003643), hypertension (MESH:D006973), graft injury (MESH:D055589), INF (MESH:C536126), glomerulonephritis (MESH:D005921), DGF (MESH:D051799), peripheral vascular disease (MESH:D016491), cardiac arrest (MESH:D006323), Chronic Kidney Disease (MESH:D051436), infection (MESH:D007239), kidney graft failure (MESH:D051437), diabetes mellitus (MESH:D003920), ESRD (MESH:D007676)
- **Chemicals:** steroids (MESH:D013256), creatinine (MESH:D003404), Daclizumab (MESH:D000077561), Tac (MESH:D016559), Ciclosporin A (MESH:D016572), MMF (MESH:D009173), anti (-), prednisolone (MESH:D011239), AZA (MESH:D001379), basiliximab (MESH:D000077552)
- **Species:** Cytomegalovirus (genus) [taxon 10358], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12936035/full.md

## References

19 references — full list in the complete paper: https://tomesphere.com/paper/PMC12936035/full.md

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Source: https://tomesphere.com/paper/PMC12936035