Overview
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
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