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The evolution of histological changes suggestive of antibody-mediated injury, in the presence and absence of donor-specific anti-HLA antibodies KU Leuven
The interplay between donor-specific anti-HLA antibodies (HLA-DSA), histology of active antibody-mediated rejection (aABMRh ), transplant glomerulopathy (cg), and graft failure in kidney transplantation remains insufficiently understood. We performed a single-center cohort study (n = 1000) including 2761 protocol and 833 indication biopsies. Patients with pretransplant HLA-DSA were more prone to develop aABMRh (OR 22.7, 95% CI, ...
Missing Self?Induced Microvascular Rejection of Kidney Allografts: A Population-Based Study KU Leuven
BACKGROUND: Circulating anti-HLA donor-specific antibodies (HLA-DSA) are often absent in kidney transplant recipients with microvascular inflammation (MVI). Missing self, the inability of donor endothelial cells to provide HLA I-mediated signals to inhibitory killer cell Ig-like receptors (KIRs) on recipient natural killer cells, can cause endothelial damage in vitro, and has been associated with HLA-DSA-negative MVI. However, missing self's ...
Risk factors, histopathological features, and graft outcome of transplant glomerulopathy in the absence of donor-specific HLA antibodies KU Leuven
Transplant glomerulopathy is established as a hallmark of chronic antibody-mediated rejection in kidney transplant patients with donor-specific HLA antibodies (HLA-DSA). The clinical importance of transplant glomerulopathy in the absence of HLA-DSA is not well established. To help define this, 954 patients (encompassing 3744 biopsies) who underwent kidney transplantation 2004-2013 were studied with retrospective high-resolution HLA genotyping of ...
Revisiting the changes in the Banff classification for antibody-mediated rejection after kidney transplantation KU Leuven
The Banff classification for antibody-mediated rejection (ABMR) has undergone important changes, mainly by inclusion of C4d-negative ABMR in Banff'13 and elimination of suspicious ABMR (sABMR) with the use of C4d as surrogate for HLA-DSA in Banff'17. We aimed to evaluate the numerical and prognostic repercussions of these changes in a single-center cohort study of 949 single kidney transplantations, comprising 3662 biopsies that were classified ...
Data-driven derivation and validation of novel phenotypes for acute kidney transplant rejection using semi-supervised clustering KU Leuven
BACKGROUND: Over the past decades, an international group of experts iteratively developed a consensus classification of kidney transplant rejection phenotypes, known as the Banff classification. Data-driven clustering of kidney transplant histologic data could simplify the complex and discretionary rules of the Banff classification, while improving the association with graft failure. METHODS: The data consisted of a training set of 3510 ...
Assessing the Complex Causes of Kidney Allograft Loss KU Leuven
BACKGROUND: Although graft loss is a primary endpoint in many studies in kidney transplantation and a broad spectrum of risk factors has been identified, the eventual causes of graft failure in individual cases remain ill studied. METHODS: We performed a single-center cohort study in 1000 renal allograft recipients, transplanted between March 2004 and February 2013. RESULTS: In total, 365 graft losses (36.5%) were identified, of which 211 ...
Clinical importance of extended second field high-resolution HLA genotyping for kidney transplantation KU Leuven
The need for extended second field high-resolution (2F-HR) HLA genotyping in kidney transplantation is debated. In a cohort of 1000 kidney transplants, we evaluated the impact of different HLA genotyping levels on the assignment of donor-specific anti-HLA antibodies (DSA) and investigated whether inference of 2F-HR genotypes from low-resolution (LR) genotypes could be used to correctly assign DSA. Based on LR genotypes, 224 pretransplant DSAs ...
The Histological Picture of Indication Biopsies in the First 2 Weeks after Kidney Transplantation KU Leuven
BACKGROUND AND OBJECTIVES: In preclinical studies, ischemia-reperfusion injury and older donor age are associated with graft inflammation in the early phase after transplantation. In human kidney transplantation, impaired allograft function in the first days after transplantation is often adjudicated to donor- and procedure-related characteristics, such as donor age, donor type, and ischemia times. DESIGN: , setting, participants, & ...
Eplet Mismatch Load and De Novo Occurrence of Donor-Specific Anti-HLA Antibodies, Rejection, and Graft Failure after Kidney Transplantation: An Observational Cohort Study KU Leuven
BACKGROUND: In kidney transplantation, evaluating mismatches of HLA eplets-small patches of surface-exposed amino acids of the HLA molecule-instead of antigen mismatches might offer a better approach to assessing donor-recipient HLA incompatibility and improve risk assessment and prediction of transplant outcomes. METHODS: To evaluate the effect of number of eplet mismatches (mismatch load) on de novo formation of donor-specific HLA antibodies ...