Evaluating Urinary CXCL10 for Enhanced Detection of Acute Rejection in Kidney Transplant Patients With Low DD-CFDNA

February 9, 2026 updated by: Virginia Commonwealth University

Evaluating Urinary CXCL10 for Enhanced Detection of Acute Rejection in Kidney Transplant Patients With Low DD-CFDNA: Diagnostic Performance and Transport Stability Across Shipping Conditions (CLEAR-CXCL10)

Kidney transplant rejection remains a significant challenge to long-term graft survival. While histological biopsy continues to be the gold standard for diagnosing rejection, noninvasive biomarkers such as donor-derived cell-free DNA (dd-cfDNA) have gained traction for their ability to detect allograft injury. However, dd-cfDNA may lack sensitivity in certain clinical scenarios particularly in cases of localized immune activation leading to false negatives despite biopsy-confirmed rejection.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

One promising biomarker is CXCL10 (C-X-C motif chemokine ligand 10), a chemokine induced by interferon-γ that plays a central role in recruiting CXCR3+ T cells during immune responses. A 2021 study by Arnau et al. found that urinary CXCL10 levels were significantly associated with Banff scores of acute graft injury and donor-specific antibodies, and could discriminate both T-cell-mediated and antibody-mediated rejection in kidney transplant recipients, identifying CXCL10 as a promising candidate non-invasive biomarker for monitoring allograft rejection.

Study Type

Observational

Enrollment (Estimated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

A total of 50 kidney transplant recipients will be included in this study:

  • 20 retrospective subjects: will be selected from the HM20019578 VCU Kidney Transplant Prospective Registry. These individuals have biopsy-confirmed acute rejection with dd-cfDNA<1% results. Frozen urine aliquots previously biobanked from these subjects will be used for CXCL10 testing.
  • 30 prospective subjects: will be enrolled at the time of a clinically indicated kidney biopsy. A single urine sample will be collected during the biopsy visit and immediately split into two equal aliquots. One aliquot will be stored and transported under refrigerated conditions, while the other will be kept under ambient conditions. Both samples will be shipped simultaneously to One Lambda for CXCL10 testing.

Description

Prospective Inclusion Criteria:

  • Age ≥18 years
  • Undergoing a clinically indicated biopsy
  • Able to provide informed consent
  • Willing to provide a urine sample and allow access to relevant clinical

Retrospective Inclusion Criteria:

  • Age ≥18 years
  • Biopsy-confirmed rejection (positive histology)
  • Donor-derived cell-free DNA<1% result at time of biopsy
  • Availability of stored urine sample collected at time of biopsy

Exclusion Criteria (applies to both arms):

  • Individuals under 18 years of age
  • Individuals unable to provide informed consent (for prospective enrollment)
  • Pregnant women
  • Prisoners
  • Adults unable to consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Retrospective (Kidney Transplant recipients)
There will be 20 Retrospective (Kidney Transplant recipients) subjects enrolled
Other: Retrospective Cohort Enrollment

Subjects for this cohort will be selected from existing research database and criteria include:

hx of kidney transplantation, clinically indicated biopsy, positive histology, <1% circulating donor-derived cell-free DNA (dd-cfDNA) result at the time of biopsy, and Availability of frozen urine samples.
Prospective (Kidney Transplant recipients)
There will be 30 Prospective (Kidney Transplant recipients) subjects enrolled
Other: Prospective Cohort Enrollment
Subjects for this cohort will be selected based on ability to provide urine sample, recent kidney transplant recipient and underwent a clinically indicated biopsy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Assess urinary CXCL10 compared to dd-cfDNA for diagnosing acute rejection in kidney transplant recipients
Time Frame: From date of inclusion until loss of follow-up, graft loss or death assessed up to 5 years.
Assess whether urinary CXCL10 concentration (pg/mL) demonstrates improved sensitivity compared to donor-derived cell-free DNA (dd-cfDNA) for diagnosing acute rejection in kidney transplant recipients, specifically among discordant cases with biopsy-confirmed rejection and dd-cfDNA levels below 1%. Urine sample collected prospectively, during clinically indicated biopsy visit. Urine sample collected retrospectively, during clinically indicated retrospective biopsy visit.
From date of inclusion until loss of follow-up, graft loss or death assessed up to 5 years.
Assess the stability of urinary CXCL10 under different transport conditions
Time Frame: From date of inclusion until loss of follow-up, graft loss or death assessed up to 5 years.
Assess the stability of urinary CXCL10 (percent recovery) under different transport conditions-refrigerated, and ambient (room temperature)-to determine whether ambient shipping is a viable alternative to cold-chain transport for clinical testing. Urine sample collected prospectively, during clinically indicated biopsy visit. Urine sample collected retrospectively, during clinically indicated retrospective biopsy visit.
From date of inclusion until loss of follow-up, graft loss or death assessed up to 5 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Compare urinary CXCL10 concentrations to assess potential degradation or variability.
Time Frame: From date of inclusion until loss of follow-up, graft loss or death assessed up to 5 years.

Compare urinary CXCL10 concentrations across the two transport conditions to assess potential degradation or variability.

  • Mean absolute difference (pg/mL)
  • Coefficient of variation (CV)
  • Bland-Altman plots to assess agreement Urine sample collected prospectively, during clinically indicated biopsy visit. Urine sample collected retrospectively, during clinically indicated retrospective biopsy visit.
From date of inclusion until loss of follow-up, graft loss or death assessed up to 5 years.
Determine whether ambient shipping (urine sample) affects the clinical reliability of CXCL10 measurements
Time Frame: From date of inclusion until loss of follow-up, graft loss or death assessed up to 5 years.

Determine whether ambient shipping (urine sample) affects the clinical reliability of CXCL10 measurements

  • CXCL10 results dichotomized using predefined clinical thresholds
  • Percent agreement and Cohen's kappa statistic calculated between transport conditions

Urine sample collected prospectively, during clinically indicated biopsy visit. Urine sample collected retrospectively, during clinically indicated retrospective biopsy visit.
From date of inclusion until loss of follow-up, graft loss or death assessed up to 5 years.
Assess the feasibility of implementing ambient (urine sample) shipping as a cost-effective alternative
Time Frame: From date of inclusion until loss of follow-up, graft loss or death assessed up to 5 years.

Assess the feasibility of implementing ambient (urine sample) shipping as a cost-effective alternative to current cold-chain methods.

  • Proportion of samples meeting laboratory acceptance criteria
  • Shipping duration summarized in hours from collection to laboratory receipt

Urine sample collected prospectively, during clinically indicated biopsy visit. Urine sample collected retrospectively, during clinically indicated retrospective biopsy visit.
From date of inclusion until loss of follow-up, graft loss or death assessed up to 5 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Virginia Commonwealth University

Collaborators

Thermo Fisher Scientific, Inc

Investigators

  • Principal Investigator: Gaurav Gupta, MD, Virginia Commonwealth University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2026

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

January 7, 2026

First Submitted That Met QC Criteria

February 9, 2026

First Posted (Actual)

February 17, 2026

Study Record Updates

Last Update Posted (Actual)

February 17, 2026

Last Update Submitted That Met QC Criteria

February 9, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • HM300000312

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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