Early progression of chronic histologic lesions in kidney transplant biopsies is not associated with HLA histocompatibility
Related Experiment Video
Updated: Jul 11, 2025
Mouse Kidney Transplantation: Models of Allograft Rejection
Published on: October 11, 2014
Rhea Jabbour1, Andreas Heinzel1, Roman Reindl-Schwaighofer1
1Division of Nephrology and Dialysis, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Insights
Human leukocyte antigen (HLA) mismatch did not significantly correlate with chronic kidney allograft lesion progression, though other factors likely contribute. De novo donor-specific antibody (dnDSA) formation was confirmed to associate with HLA mismatch and microvascular inflammation (MVI).
Area of Science:
- Nephrology
- Transplantation Immunology
- Histopathology
Background:
- Early progression of chronic histologic lesions is a primary cause of kidney allograft loss.
- Understanding factors influencing chronic lesion development is crucial for improving long-term transplant outcomes.
- Human leukocyte antigen (HLA) compatibility is a key consideration in transplantation.
Purpose of the Study:
- To investigate the association between HLA histocompatibility and the progression of chronic histologic lesions in kidney allografts within the first year post-transplant.
- To compare findings with established associations of de novo donor-specific antibody (dnDSA) formation with HLA mismatch and microvascular inflammation (MVI).
Main Methods:
- Retrospective cohort study of 117 adult kidney transplant recipients with surveillance biopsies at 3 and 12 months.
- Histologic lesion scoring using the Banff classification.
- Calculation of various HLA mismatch scores (eplet, PIRCHE-II, HLA-EMMA, whole antigen) and quantification of dnDSA formation.
Main Results:
- Over one-third of patients showed progression of chronic lesion scores (ct, ci, ah, i-IFTA) by at least one Banff grade between 3 and 12 months.
- No significant association was found between most HLA mismatch scores and histologic lesion progression, except for arteriolar hyalinosis (ah) with HLA-EMMA DRB1.
- Established associations of dnDSA formation with HLA mismatch and MVI were confirmed (OR = 5.31).
Conclusions:
- While HLA mismatch and alloimmune response are linked, other factors appear to drive the early progression of chronic kidney allograft lesions.
- Further research is needed to identify these additional contributing factors to mitigate graft attrition.
Background:
Early progression of chronic histologic lesions in kidney allografts represents the main finding in graft attrition. The objective of this retrospective cohort study was to elucidate whether HLA histocompatibility is associated with progression of chronic histologic lesions in the first year post-transplant. Established associations of de novo donor-specific antibody (dnDSA) formation with HLA mismatch and microvascular inflammation (MVI) were calculated to allow for comparability with other study cohorts.
Methods:
We included 117 adult kidney transplant recipients, transplanted between 2016 and 2020 from predominantly deceased donors, who had surveillance biopsies at 3 and 12 months. Histologic lesion scores were assessed according to the Banff classification. HLA mismatch scores [i.e. eplet, predicted indirectly recognizable HLA-epitopes algorithm (PIRCHE-II), HLA epitope mismatch algorithm (HLA-EMMA), HLA whole antigen A/B/DR] were calculated for all transplant pairs. Formation of dnDSAs was quantified by single antigen beads.
Results:
More than one-third of patients exhibited a progression of chronic lesion scores by at least one Banff grade in tubular atrophy (ct), interstitial fibrosis (ci), arteriolar hyalinosis (ah) and inflammation in the area of interstitial fibrosis and tubular atrophy (i-IFTA) from the 3- to the 12-month biopsy. Multivariable proportional odds logistic regression models revealed no association of HLA mismatch scores with progression of histologic lesions, except for ah and especially HLA-EMMA DRB1 [odds ratio (OR) = 1.10, 95% confidence interval (CI) 1.03-1.18]. Furthermore, the established associations of dnDSA formation with HLA mismatch and MVI (OR = 5.31, 95% CI 1.19-22.57) could be confirmed in our cohort.
Conclusions:
These data support the association of HLA mismatch and alloimmune response, while suggesting that other factors contribute to early progression of chronic histologic lesions.
Related Concept Videos
01:28Kidney Transplant I: Introduction
01:26Kidney Transplant II: Surgical Procedure
01:25Chronic Kidney Disease I: Introduction
01:29Acute Kidney Injury III: Clinical Manifestations
01:16Kidney Transplant III: Nursing Management
01:29Acute Kidney Injury II: Pathophysiology