Deep Phenotyping of the Renal Allograft to Prognosticate Clinical Outcomes

NCT06438107 | Not Yet Recruiting

• 1 other identifier: STUDY21090074
• Study Type: observational
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Renal Transplant Rejection

Keywords

Organ rejection; Acute rejection

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants with Biopsy Proven Acute Rejection at one year

  Percentage biopsy proven acute rejection either on a surveillance biopsy or a for-cause biopsy in the First Post-Transplant Year

  1 year

• Degree of Correlation of Acute Rejection Transcriptional Changes Within the Infiltrating Inflammatory Cells at one year

  Degree of Correlation of Transcriptional Changes Within the Infiltrating Inflammatory Cells Assessed by scRNA Sequencing in the First Post-Transplant Year

  1 year

• Percentage of Correlation of Transcriptional Changes Within the Renal Parenchymal Cells at one year

  Percentage Correlation of Acute Rejection Transcriptional Changes Within the Renal Parenchymal Cells Assessed by scRNA Sequencing in the First Post-Transplant Year

  1 year

Secondary Outcomes (8)

• Percentage of Histological Persistence of Rejection at one year

  1 year

• Degree of Correlation of Histological Transcriptional Changes Within the Infiltrating Inflammatory Cells at one year

  1 Year

• Degree of Correlation of Histological Transcriptional Changes Within the Renal Parenchymal Cells at one year

  1 Year

• Percentage of Participants with Biopsy Proven Acute Rejection at Year 3

  3 Years

• Degree of Correlation of Acute Rejection Transcriptional Changes Within the Infiltrating Inflammatory Cells at Year 3

  3 Years

Study Arms (1)

Renal transplantation recipients

Living donor and deceased donor renal transplant recipients. There is no intervention to be administered.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult living donor or deceased donor renal transplant recipients

You may qualify if:

• All adult living or deceased donor renal transplant recipients (age ≥ 18 years), irrespective of gender, race, or ethnic background.
• Able to understand and provide inform consent.

You may not qualify if:

• Medical contraindications to undergo renal biopsy (use of long-term anticoagulation, low platelet count of \<100,000/uL)
• Cause of ESRD likely to recur in transplant: Hemolytic uremic syndrome (HUS)
• Not maintained on standard of care immunosuppression therapy (Thymoglobulin induction followed by tacrolimus and mycophenolate maintenance)

Sponsors & Collaborators

• University of Pittsburgh: lead

Study Sites (1)

UPMC

Pittsburgh, Pennsylvania, 15213, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Renal biopsy core tissue specimens, blood plasma and PBMC samples

Study Officials

• Aravind Cherukuri, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Beth Elinoff, RN

CONTACT

412-624-6611; elinbd@upmc.edu

Aravind Cherukuri, MD

CONTACT

4125250671; cherukuria@upmc.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine and Surgery

Study Record Dates

• First Submitted: February 19, 2024
• First Posted: May 31, 2024
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): July 1, 2030
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)