Deep Phenotyping of the Renal Allograft to Prognosticate Clinical Outcomes
University of Pittsburgh
Summary
The goal of this observational study is to determine phenotypic, transcriptional, and epigenetic underpinnings of renal allograft rejection in renal transplant rejection. The main questions it aims to answer are: * To determine the phenotype, frequency, location, and the inter-cellular interactions between the cells that constitute intra-graft inflammatory infiltrate in acute ejection. * To determine the phenotype, frequency, location, and the inter-cellular interactions between the cells that constitute intra-graft inflammatory infiltrate in recurrent/recalcitrant rejection vs. rejection that resolves with therapy. * To generate a scRNA sequencing (scRNAseq) map of the intra-graft immune cells and the renal parenchymal cells and compare the transcriptional and epigenetic changes within these cells in recurrent/recalcitrant rejection vs. rejection that resolves with therapy. * To determine phenotypic changes associated with chronic rejection. Participants will be asked to provide the following research specimens: * Renal biopsy specimens at the following timepoints: day of transplantation (pre-implantation and post-perfusion); routine protocol biopsies at 3 months and 12 months; and clinically indicated for-cause biopsies at any timepoint from time-0 to 1-yr post-transplantation. The 1st research core will be used for routine histopathological examination and left over tissue from this core will be used for deep phenotyping using multiparameter immunophenotyping, and digital spatial profiling. The second research core will be used for extraction of cells and nuclei for scRNAseq and snATACseq. * Blood samples will be processed to obtain plasma (for cytokine, chemokine and DSA measurements) and PBMC (for deep phenotyping and molecular analyses). For each collection timepoint, up to 75 mL (about 5 tablespoons) will be collected. * Prospective clinical data and outcomes will be collected from participant medical records. * Follow-Up Period: For-cause biopsies from 1-yr to 5-yr post-transplantation (by the transplant nephrologist): no additional cores will be obtained for research from these biopsies. The left-over tissue from the clinically indicated biopsy cores will be analyzed by deep phenotyping and digital spatial profiling. Blood samples will be processed to obtain plasma (for cytokine, chemokine and DSA measurements) and PBMC (for deep phenotyping and molecular analyses).
Description
This study is exploratory in nature and aims to elucidate the phenotypic, transcriptional, and epigenetic underpinnings of renal transplant rejection. The study is designed to provide improved understanding of the regulation of intra-graft alloimmune response in the renal transplant recipients. In this single center, prospective, longitudinal, observational cohort study, sequential assessment of renal biopsies will be performed at baseline (pre-implantation), 3 months and at one-year post-transplantation in addition to any for-cause biopsies within the first five years post-transplantation. B…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. All adult living or deceased donor renal transplant recipients (age ≥ 18 years), irrespective of gender, race, or ethnic background. 2. Able to understand and provide inform consent. Exclusion Criteria: 1. Medical contraindications to undergo renal biopsy (use of long-term anticoagulation, low platelet count of \<100,000/uL) 2. Cause of ESRD likely to recur in transplant: Hemolytic uremic syndrome (HUS) 3. Not maintained on standard of care immunosuppression therapy (Thymoglobulin induction followed by tacrolimus and mycophenolate maintenance)
Location
- UPMCPittsburgh, Pennsylvania