Evidence map›Paper›PMID 40387242›Full record

ArticleHLA2025

Repeated HLA-DRB1 and HLA-DQB1 Mismatches Without Preformed DSA Affect Graft Survival, Rejection and DSA Development: A Multicenter Analysis.

D A J van den Broek, S Meziyerh, D van der Helm, J C van den Born, J S F Sanders, B G Hepkema, J van de Wetering, J A Kal van Gestel, J Kers, C van Kooten and 3 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in HLA, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. The Progress and Challenges of Implementing HLA Molecular Matching in Clinical Practice.Transplant international : official journal of the European Society for Organ Transplantation · 2025
    Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

D A J van den BroekDivision of Nephrology, Department of Internal Medicine, Leiden University Medical Center (LUMC), Leiden University, Leiden, the Netherlands.ORCID 0000-0001-7135-4752
S MeziyerhDivision of Nephrology, Department of Internal Medicine, Leiden University Medical Center (LUMC), Leiden University, Leiden, the Netherlands.ORCID 0000-0001-7694-8381
D van der HelmDivision of Nephrology, Department of Internal Medicine, Leiden University Medical Center (LUMC), Leiden University, Leiden, the Netherlands.ORCID 0000-0002-8227-3998
J C van den BornDepartment of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID 0000-0003-2637-4046
J S F SandersDepartment of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID 0000-0002-0904-3969
B G HepkemaTransplantation Immunology, Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.ORCID 0000-0002-0445-8217
J van de WeteringDepartment of Internal Medicine, Erasmus Medical Center Transplant Institute, University Medical Center, Rotterdam, the Netherlands.ORCID 0000-0001-9117-2630
J A Kal van GestelDepartment of Internal Medicine, Erasmus Medical Center Transplant Institute, University Medical Center, Rotterdam, the Netherlands.ORCID 0000-0002-6270-560X
J KersLeiden Transplant Center, Leiden University Medical Center (LUMC), Leiden University, Leiden, the Netherlands.ORCID 0000-0002-2418-5279
C van KootenDivision of Nephrology, Department of Internal Medicine, Leiden University Medical Center (LUMC), Leiden University, Leiden, the Netherlands.ORCID 0000-0002-6257-0899
J I RotmansDivision of Nephrology, Department of Internal Medicine, Leiden University Medical Center (LUMC), Leiden University, Leiden, the Netherlands.ORCID 0000-0001-9682-6234
A P J de VriesDivision of Nephrology, Department of Internal Medicine, Leiden University Medical Center (LUMC), Leiden University, Leiden, the Netherlands.ORCID 0000-0002-9284-3595
D L RoelenLeiden Transplant Center, Leiden University Medical Center (LUMC), Leiden University, Leiden, the Netherlands.ORCID 0000-0002-1846-1193

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Repeat transplantations represent up to 20% of all kidney transplants. Whereas repeat transplantations in the presence of circulating donor-specific HLA-antibodies are generally avoided, the risk of repeated HLA-mismatches (RMM) without detectable antibodies remains debated. This multicenter study evaluated the hazard of RMM, stratified by HLA-class, on transplant outcomes in the absence of preformed donor-specific antibodies. We included repeat kidney transplant recipients from January 2009 onward with available HLA typing for HLA-A, -B, -C, -DRB1, -DRB3/4/5 and -DQB1 from current and previous donors. RMM were defined at the split serological antigen level, excluding patients with only HLA-DP or HLA-DRB3/4/5 RMM. Patients were included if: (a) preformed donor-specific HLA-antibodies (DSA) had never been detected and (b) this was confirmed by Luminex assays within 6 months pre-transplantation. A competing risk model, adjusting for demographic factors and total HLA-mismatch load while accounting for death as a competing risk, showed that HLA-DRB1 and/or HLA-DQB1 RMM significantly increased the risk of graft loss within 1 year post-transplant (HR 3.75 [95% CI 1.51-9.34], p = 0.004). Cox proportional hazard models further linked these HLA-class II RMM to higher risks of biopsy-proven rejection (HR 1.98 [95% CI 1.04-3.76], p = 0.037) and DSA development (HR 9.89 [95% CI 1.92-50.99], p = 0.006), while no significant risks were observed for HLA-class I RMM. Sensitivity analyses in patients screened for pretransplant DSA via single antigen bead assays, those with similar immunosuppression, and those with allelic RMM further confirmed these findings. These results suggest that avoiding HLA-DRB1 and HLA-DQB1 RMM, when feasible, may improve transplant outcomes.

Indexed as

Graft RejectionGraft SurvivalHLA-DQ beta-ChainsHLA-DRB1 ChainsIsoantibodiesKidney TransplantationAdultFemaleHistocompatibility TestingHumansMaleMiddle AgedHLA-DQB1 antigenHLA-DQ beta-ChainsHLA-DRB1 ChainsIsoantibodiesallograft survivalHLArejectionrenal transplantationrepeated mismatchrisk‐stratificationsensitization

Identifiers

PMID40387242
PMCPMC12087429

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.