Proteogenomic Monitoring and Assessment of Kidney Transplant Recipients

NCT ID: NCT01531257

Last Updated: 2025-02-17

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 1000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2010-04-30
• Study Completion Date: 2026-12-31

Brief Summary

Chronic Allograft Nephropathy (CAN)/Interstitial fibrosis and Tubular Atrophy (IFTA) is responsible for most kidney transplant failures. CAN/IFTA on a 3 month kidney biopsy strongly predicts graft survival long term. CAN/IFTA remains a vexing problem for clinicians because current monitoring tools, namely the serum creatinine concentration, are not sensitive to early changes in glomerular filtration rate (GFR) or to histologic damage.

Despite advances in prevention of acute rejection (AR), it is still a significant and potentially devastating complication of solid organ transplantation. One strategy to reduce the risk of rejection is to perform kidney biopsies to detect subclinical acute rejection (SCAR) and treat to prevent progression to rejection. There is evidence that treating SCAR can prevent further immune mediated injury to the kidney, a precursor to CAN/IFTA.

Kidney biopsies provide better information but are limited due to safety concerns, patient preference and cost issues. Better, early and less invasive markers of CAN/IFTA will allow early intervention as well as improved graft and better patient outcomes.

This study seeks to validate specific proteogenomic biomarker panels for AR and CAN/IFTA in a prospective blood, urine and kidney tissue monitoring study of kidney transplant recipients who will be scheduled for standard of care biopsies.

Detailed Description

This is a single-center sample study. A total number of 1000 subjects will be consented and enrolled at Northwestern University Transplant clinic at the time of kidney biopsy. At our clinic, protocol biopsy may be performed at 3 months, 12 months , 24 months or any other time the doctor feels necessary post transplant in all kidney recipients. Kidney transplant recipients may also go under "for cause" biopsy procedure at any time point before/after or in between these protocol biopsy time points. Such causes of biopsy include increase in serum creatinine level, decrease in urine output, and/or pain at graft site.

Full blood tube set, urine sample for proteomics and flow cytometry of urinary sediment, and an extra core kidney biopsy tissue for gene expression profiling will be collected from subjects at the time of any biopsies obtained during the study course. These specimen samples will be sent to Rules-Based Medicine (RBM) for proteomic analysis. Whole genome expression profiling will be done using Affymetrix GeneChips at The Scripps Research Institute.

We estimate that we will find at least 500 subjects with diagnostic CAN/IFTA histology (Banff 1-2) between the 3 months and 12 months post transplant protocol biopsies based on a 50% incidence in the literature and our own experience. We also estimate that there will be 10% (10 subjects) incidence of clinical rejection by the end of 12 months identified initially by an acute rise in the serum creatinine and confirmed by a biopsy. Lastly, we estimate a 10% (10 subjects) incidence of subclinical acute rejection with stable renal function detected by the protocol kidney biopsies.

Conditions

Acute Rejection (AR) of Transplanted Kidney; Chronic Allograft Nephropathy (CAN); Interstitial Fibrosis (IF); Tubular Atrophy (TA)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Kidney Transplant Recipients

The intention of our biomarker panel is to be broadly applicable to all patients with a kidney transplant with the assumption that there are common underlying molecular mechanisms of AR and CAN/IFTA 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. We chose not to include patients with dual organ transplants so that we could isolate the molecular signal we are studying.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

1. Male and female recipients of all races, ≥18 years of age.

2. Patients undergoing primary or subsequent deceased-donor or living donor kidney 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. Need for combined organ transplantation with an extra-renal organ and/or islet cell transplant.

2. Recipients of previous non-renal solid organ and/or islet cell transplantation.

3. Infection with HIV.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Transplant Genomics, Inc.

INDUSTRY

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Sook Hyeon Park

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sook H Park, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern University

Chicago, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Martha Castellini, BA

Role: CONTACT

martha.castellini@northwestern.edu

Facility Contacts

Martha Castellini, BA

Role: primary

martha.castellini@northwestern.edu

Other Identifiers

STU 25946

Identifier Type: -

Identifier Source: org_study_id