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)
Virginia Commonwealth University
Summary
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.
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.
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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 wo…
Interventions
- OtherRetrospective 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.
- OtherProspective 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
Location
- Virginia Commonwealth UniversityRichmond, Virginia