Abstract: TH-PO0890
Replicating the Human Leukocyte Antigen (HLA)-Independent Association of Non-HLA Donor/Recipient Genomic Mismatches with Kidney Allograft Survival in a Contemporary Cohort
Session Information
- Transplantation: Basic Research
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 2101 Transplantation: Basic
Authors
- Oberbauer, Rainer, Medical University of Vienna, Department of Nephrology & Dialysis, Vienna, Austria
- Kammer, Michael, Medical University of Vienna, Department of Nephrology & Dialysis, Vienna, Austria
- Heinzel, Andreas, Medical University of Vienna, Department of Nephrology & Dialysis, Vienna, Austria
- Reindl-Schwaighofer, Roman, Medical University of Vienna, Department of Nephrology & Dialysis, Vienna, Austria
- Shoebridge, Stephen, Medical University of Vienna, Department of Nephrology & Dialysis, Vienna, Austria
- Hu, Karin, Medical University of Vienna, Department of Nephrology & Dialysis, Vienna, Austria
- Kainz, Alexander, Medical University of Vienna, Department of Nephrology & Dialysis, Vienna, Austria
- Niemann, Matthias, Pirche AG, Berlin, Germany
Background
In 2019 we published for the first time the HLA mismatch (HLA-MM) independent association of non-HLA donor/recipient (D/R) genomic mismatches (non-HLA-MM) with graft survival in first deceased donor kidney transplants. Here we replicate this finding in a larger contemporary cohort.
Methods
We utilized the Vienna Kidney Transplant Cohort, a prospective open cohort study initiated in 2012. From 2012 - 2023, a total of 1,680 transplants were performed and 854 recipients of a first deceased donor transplant were available for the replication. Two-field HLA-typing and whole exome sequencing (WES) were performed. WES data were processed into annotated SNPs with GATK and Ensembl Variant Effect Predictor. Subcellular location was used to restrict to immune-accessible proteins and the number of non-synonymous SNP mismatches was determined. For HLA-MM PIRCHE-T2 scores were computed on 5 HLA loci. The association of non-HLA and HLA scores with death censored graft failure was evaluated using Kaplan-Meier (KM) analysis and Cox proportional hazard models.
Results
The median recipient and donor ages were 58 and 57 years, respectively. Among recipients 34% were female. In the follow up period 117 grafts were lost and 256 recipients died. KM analysis of high and low non-HLA-MM stratified by the median showed reduced graft survival for higher mismatch load (Fig 1a). Analysis of the continuous score in a Cox model adjusted for key predictors of graft survival confirmed the HLA-MM independent association of the non-HLA-MM score with graft survival (Fig 1b). The strength of association of non-HLA and HLA-MM per interquartile range with graft survival were similar to our previous study.
Conclusion
We successfully replicated the findings from our index study regarding the association between non-HLA-MM and graft survival. This once more highlights that in addition to HLA compatibility non-HLA D/R compatibility plays an important role in transplantation success.