Automated Urinary Chemokine Assays for Noninvasive Detection of Kidney Transplant Rejection: A Prospective Cohort Study

Rationale & ObjectivePrior studies have demonstrated the diagnostic potential of urinary chemokines CXCL9 and CXCL10 for kidney transplant rejection. However, their benefit in addition to clinical information has not been demonstrated. We evaluated the diagnostic performance for detecting acute rejection of urinary CXCL9 and CXCL10 when integrated with clinical information.Study DesignSingle-center prospective cohort study.Setting& Participants: We analyzed 1559 biopsy-paired urinary samples from 622 kidney transplants performed between April 2013 and July 2019 at a single transplant center in Belgium. External validation was performed in 986 biopsy-paired urinary samples.Tests ComparedWe quantified urinary CXCL9 (uCXCL9) and CXCL10 (uCXCL10) using an automated immuno-assay platform and normalized the values to urinary creatinine. Urinary chemokines were incorporated into a multivariable model with routine clinical markers (eGFR, donor-specific antibodies, and polyoma viremia) (integrated model). This model was then compared to the tissue diagnosis according to the Banff classification for acute rejection.OutcomeAcute rejection detected on kidney biopsy using the Banff classification.ResultsChemokines, integrated with routine clinical markers had high diagnostic value for detection of acute rejection (N=150) (ROC AUC 81.3%, 95% CI 77.6-85.0). The integrated model would help avoid 59 protocol biopsies per 100 patients when the risk for rejection is predicted to be below 10%. The performance of the integrated model was similar in the external validation cohort.LimitationsThe cross-sectional nature obviates investigating the evolution over time and prediction of future rejection.ConclusionsThis study suggests that the use of an integrated model of urinary chemokines and clinical markers for non-invasive monitoring of rejection would enable a reduction in the number of biopsies. Urinary chemokines may be useful non-invasive biomarkers whose use should be further studied in prospective randomized trials to clarify their role in guiding clinical care and the use of biopsies to detect rejection after kidney transplantation.