Proteogenomic Monitoring and Assessment of Liver Transplant Recipients ("Mini-Liver")

This study is being done to test blood, urine and tissue samples to see if this can help decide if CKD (Chronic Kidney Disease), AR (Acute Rejection) and HCV (Hepatitis C Virus) can be identified in its early stages. CKD damage to the kidneys, AR and HCV all lower the body's ability to function properly. Early detection of these conditions could assist with successful treatment and possibly lead to less repeat organ transplants.

Study Overview

• Status: Recruiting
• Conditions: Hepatitis C; Chronic Kidney Disease; Liver Transplant; Acute Rejection

Detailed Description

With the advent of more sensitive molecular techniques, biomarkers of kidney transplant rejection have been proposed that are potentially much more sensitive, specific and rapidly testable than conventional predictors of graft function such as GFR or tissue biopsies. Some of the early biomarkers during this evolution were the Cytotoxic T-cell (CTL) transcripts like perforin, granzyme B and fas ligand 11-13 for acute rejection. In the case of CAN/IFTA and CKD the molecular mechanisms and testable biomarkers also remain unclear. A few studies have reported the involvement of TGF-beta, extracellular matrix proteins like fibronectin and thrombopondin and tissue inhibitors of metalloproteins (TIMPs) as being upregulated in patients with Chronic Allograft Nephropathy (CAN/IFTA). Most of these studies were done in kidney transplant biopsies and the challenge of testing their expression and correlation in PBL as a minimally invasive tool was only addressed in a few studies. Another limitation of these first studies was the lack of the power to profile genes globally. To this end the advent of DNA microarrays has brought about a quantum leap in the ability to profile thousands of genes simultaneously. Thus far, microarray analysis has been reported in kidney transplant studies implicating gene signatures for acute rejection in transplant biopsies as well as for the first time by us in peripheral blood. To our knowledge only two studies have tried to profile CAN/IFTA in peripheral blood. A recent study attempted to validate three genes that were derived from a microarray analysis of kidney biopsies using RT-qPCR. All three genes were significantly differentially expressed in urine but not in PBL. Another study using microarrays showed that among a panel of 49 peripheral blood genes that were purported to distinguish "operational tolerance" in kidney rejection, 33 genes could also distinguish "chronic rejection" with 86% specificity.

Most of the studies in the literature, including our own, as well as our more recent unpublished peripheral blood gene expression studies of AR and CAN/IFTA reveal clear molecular signatures for both these forms of transplant outcomes. In sum, these data establish a first proof of concept that peripheral blood gene expression profiling can be used to develop markers of kidney allograft rejection and chronic kidney injury.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Misael Villegas, BA; Email: misael.villegas@northwestern.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Northwestern Memorial Hospital
      • Contact: Jairo Chavez, BA; Email: jairo.chavez@northwestern.edu
      • Contact: Misael Villegas, BA; Email: misael.villegas@northwestern.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The intention of our biomarker panel is to be broadly applicable to all patients with liver transplant with the assumption that there are common underlying molecular mechanisms of CKD and AR (and HCV) that can be detected hopefully at early stages of disease. We therefore want to validate and test our biomarker panel in a broad collection of patient types.

Description

Inclusion Criteria:

1. Male and female recipients of all races, ≥18 years of age.
2. Patients undergoing primary or subsequent living or deceased donor liver transplantation.
3. Subject and/or guardian must be able to provide informed consent.
4. Subject and/or guardian must be able to comply with the study protocol.

Exclusion Criteria:

1. Inability or unwillingness of a participant and/or guardian to provide informed consent.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proteogenomic Biomarkers for CKD, AR and HCV	To validate specific proteogenomic biomarker panels for CKD and AR (and HCV) in a prospective serial blood and urine monitoring study of liver transplant recipients	At time of liver biopsy

Collaborators and Investigators

• Sponsor: Northwestern University
• Collaborators: The Scripps Research Institute
• Investigators: Principal Investigator: Josh Levitsky, MD, Northwestern University

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: July 17, 2012
• First Submitted That Met QC Criteria: July 17, 2012
• First Posted (Estimated): July 19, 2012

Study Record Updates

• Last Update Posted (Estimated): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Urologic Diseases; Disease Attributes; Liver Diseases; Renal Insufficiency; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Hepatitis C
• Other Study ID Numbers: STU 26737