A5078233658- Renal Transplantation Outcomes and Treatments
- Transplantation: Methods and Outcomes
- Organ Transplantation Techniques and Outcomes
- Renal Diseases and Glomerulopathies
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Complement system in diseases
- Cytomegalovirus and herpesvirus research
- Renal and Vascular Pathologies
- Monoclonal and Polyclonal Antibodies Research
- Bladder and Urothelial Cancer Treatments
- Urological Disorders and Treatments
- Advanced Biosensing Techniques and Applications
- Pediatric Urology and Nephrology Studies
- Reproductive System and Pregnancy
- Blood groups and transfusion
- Viral Infections and Immunology Research
- Pancreatic function and diabetes
- Polyomavirus and related diseases
- Renal cell carcinoma treatment
- Organ Donation and Transplantation
- Kidney Stones and Urolithiasis Treatments
- Diabetes and associated disorders
- Urinary and Genital Oncology Studies
- Metabolism and Genetic Disorders
University of Wisconsin–Madison
2019-2025
University of Wisconsin Health
2023-2025
University of Wisconsin System
2023-2024
Hospital Universitario Virgen Macarena
2024
UW Health University Hospital
2020
University of Alberta Hospital
2010-2019
University of Alberta
2009-2018
The Metabolomics Innovation Centre
2008-2018
Alberta Hospital Edmonton
2011-2018
Universidad Continental
2018
We prospectively studied kidney transplants that progressed to failure after a biopsy for clinical indications, aiming assign cause every failure. followed 315 allograft recipients who underwent indication biopsies at 6 days 32 years posttransplant. Sixty kidneys in the follow-up period (median 31.4 months). Failure was rare T-cell-mediated rejection and acute injury common antibody-mediated or glomerulonephritis. developed rules using diagnoses, HLA antibody data explain each Excluding four...
We studied the phenotype of late kidney graft failure in a prospective study unselected transplant biopsies taken for clinical indications. analyzed histopathology, HLA antibodies and death-censored survival 234 consecutive from 173 patients, 6 days to 31 years posttransplant. Patients with (>1 year) frequently displayed donor-specific antibody (particularly class II) microcirculation changes, including glomerulitis, glomerulopathy, capillaritis, capillary multilayering C4d staining. Grafts...
To explore the mechanisms of antibody-mediated rejection (ABMR) in kidney transplants, we studied transcripts expressed clinically indicated biopsies from patients with donor-specific antibody (DSA). Comparison DSA-positive versus DSA-negative revealed 132 differentially transcripts: all were associated class II DSA but none I DSA. Many ABMR also T-cell-mediated (TCMR), reflecting shared molecular features. Removal created 23 selective (DSASTs). Some DSASTs (6/23) showed high expression NK...
Antibody-mediated rejection is the major cause of kidney transplant failure, but histology-based diagnostic system misses most cases due to its requirement for C4d positivity. We hypothesized that gene expression data could be used test biopsies presence antibody-mediated rejection. To develop a molecular test, we prospectively assigned diagnoses, including C4d-negative rejection, 403 indication from 315 patients, based on histology (microcirculation lesions) and donor-specific HLA antibody....
Export Late antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Uncontrolled studies have suggested efficacy the proteasome inhibitor bortezomib, but no systematic trial has been undertaken to support its use in ABMR. In this randomized, placebo-controlled (the Bortezomib Antibody-Mediated Kidney Transplant Rejection [BORTEJECT] Trial), we investigated whether two cycles bortezomib (each cycle: 1.3 mg/m2 intravenously on days 1, 4, 8, and 11) prevent GFR...
Antibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or who develop de novo DSA. However, how these processes compare terms of allograft injury and outcome has not been addressed. From a cohort 771 kidney biopsy specimens from two North American five European centers, we performed systematic assessment clinical biologic parameters, histopathology, circulating DSA, gene expression for all ABMR ( n =205). Overall, 103 (50%) had DSA...
The prevalent renal transplant population presents an opportunity to observe the adaptive changes in alloimmune response over time, but such studies have been limited by uncertainties conventional biopsy diagnosis of T cell-mediated rejection (TCMR) and antibody-mediated (ABMR). To circumvent these limitations, we used microarrays methods investigate 703 unselected biopsies taken 3 days 35 years post-transplant from North American European centers. Using methods, diagnosed 205 specimens...
The XVI-th Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from 19th-23rd September 2022, as a joint meeting with the Canadian Society of Transplantation. To mark 30th anniversary first Classification, pre-meeting discussions were on past, present, and future Classification. This report is summary highlights that most important terms their effect including around microvascular inflammation biopsy-based transcript analysis diagnosis. In post-meeting survey, agreement...
Kidney transplant recipients that develop signs of renal dysfunction or proteinuria one more years after transplantation are at considerable risk for progression to failure. To assess the kidney this time, a "for-cause" biopsy is performed, but provides little indication as which will go on organ In an attempt identify molecules could provide information, we used microarrays analyze gene expression in 105 for-cause biopsies taken between 1 and 31 transplantation. Using supervised principal...
We studied the significance of microcirculation inflammation in kidney transplants, including 329 indication biopsies from 251 renal allograft recipients, who were mostly nonpresensitized (crossmatch negative). Glomerulitis (g) and peritubular capillaritis (ptc) often associated with antibody-mediated rejection (65% 75%, respectively), but also found other diseases absence donor-specific antibody (DSA): T-cell-mediated (ptc, g), glomerulonephritis acute tubular necrosis (ptc). To develop...
Antibody-mediated rejection (AMR) contributes to heart allograft loss. However, an important knowledge gap remains in terms of the pathophysiology AMR and how detection immune activity, injury degree, stage could be improved by intragraft gene expression profiling.We prospectively monitored 617 transplant recipients referred from 4 French centers (January 1, 2006-January 2011) for AMR. We compared patients with (n=55) a matched control group 55 without characterized all using histopathology...
The recent recognition that antibody-mediated rejection (ABMR) is the major cause of kidney transplant loss creates strong interest in its pathogenesis. We used microarray analysis biopsies to identify changes pure ABMR. found ABMR transcript initial Discovery Set were strongly conserved a subsequent Validation Set. In Combined 703 biopsies, 2603 transcripts significantly changed (FDR < 0.05) versus all other biopsies. cultured cells, associated with expressed endothelial e.g. cadherins CDH5...
Antibody-mediated rejection (ABMR) is the leading cause of kidney allograft loss. We investigated whether addition gene expression measurements to conventional methods could serve as a molecular microscope identify kidneys with ABMR that are at high risk for failure. studied 939 consecutive recipients Necker Hospital (2004-2010; principal cohort) and 321 Saint Louis (2006-2010; validation assessed patients in first 1 year post-transplant. In features, we microarray-based transplant biopsy...
Export Complement-activating anti-HLA donor-specific antibodies (DSAs) are associated with impaired kidney transplant outcome; however, whether these induce a specific rejection phenotype and influence response to therapy remains undetermined. We prospectively screened 931 recipients for complement-activating DSAs used histopathology, immunostaining, allograft gene expression assess phenotypes. Effector cells were evaluated using in vitro human cell cultures. Additionally, we assessed the...
We used expression microarrays to characterize the changes most specific for pure T cell–mediated rejection (TCMR) compared other diseases including antibody-mediated in 703 human kidney transplant biopsies, using a Discovery Set–Validation Set approach. The of thousands transcripts—fold change and association strength—changed pattern that was highly conserved between Validation sets, reflecting hierarchy cell signaling, costimulation, antigen-presenting (APC) activation interferon-gamma...
We studied the clinical, histologic, and molecular features distinguishing DSA-negative from DSA-positive molecularly defined antibody-mediated rejection (mABMR). analyzed mABMR biopsies with available DSA assessments INTERCOMEX study: 148 versus 248 DSA-positive, compared 864 no (excluding TCMR Mixed). DSA-positivity varied stage: early-stage (EABMR) 56%; fully developed (FABMR) 70%; late-stage (LABMR) 58%. patients were usually sensitized, 60% being HLA antibody-positive. Compared mABMR,...
Trifecta (ClinicalTrials.gov #NCT04239703) is a prospective trial defining relationships between donor-derived cell-free DNA (dd-cfDNA), donor-specific antibody (DSA), and molecular findings in kidney transplant biopsies. Previous analyses of double results showed dd-cfDNA was strongly associated with rejection-associated molecules the biopsy. The present study analyzed triple 280 biopsies, focusing on question levels DSA-negative antibody-mediated rejection (AMR).