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.
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
Individuals under 18 years of age
Individuals unable to provide informed consent (for prospective enrollment)
Pregnant women
Prisoners
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.
Other
Other
Retrospective Cohort Enrollment
Other interventionSubjects 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 Cohort Enrollment
Other interventionSubjects for this cohort will be selected based on ability to provide urine sample, recent kidney transplant recipient and underwent a clinically indicated biopsy
Assess urinary CXCL10 compared to dd-cfDNA for diagnosing acute rejection in kidney transplant recipients
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.
Assess the stability of urinary CXCL10 under different transport conditions
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.
Compare urinary CXCL10 concentrations to assess potential degradation or variability.
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.
Determine whether ambient shipping (urine sample) affects the clinical reliability of CXCL10 measurements
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.
Assess the feasibility of implementing ambient (urine sample) shipping as a cost-effective alternative
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.
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Virginia Commonwealth University
Lead sponsor
Thermo Fisher Scientific, Inc
Collaborator
