17 July 2024 : Original article
[In Press] Urinary Chemokines CXCL9 and CXCL10 Are Non-Invasive Biomarkers of Kidney Transplant Rejection
Ernesta Mačionienė 1ABCDEFG, Martynas Simanavičius2BE, Monika Vitkauskaitė1BC, Alvita Vickienė1B, Roberta Staučė3B, Artūras Vinikovas3B, Marius Miglinas1ADEFDOI: 10.12659/AOT.944762
Ann Transplant In Press; DOI: 10.12659/AOT.944762
Available online: 2024-07-17, In Press, Corrected Proof
Publication in the "In-Press" formula aims at speeding up the public availability of the pending manuscript while waiting for the final publication. The assigned DOI number is active and citable. The availability of the article in the Medline, PubMed and PMC databases as well as Web of Science will be obtained after the final publication according to the journal schedule
Abstract
BACKGROUND
Rejection is the main cause of kidney allograft failure, and kidney biopsy is the criterion standard method to diagnose it. However, non-invasive techniques to detect kidney transplant rejection are necessary. This study aimed to evaluate urinary chemokines CXCL9 and CXCL10 as potential biomarkers of kidney transplant rejection and to analyze chemokine association with allograft prognosis.
MATERIAL AND METHODS
We collected 117 urine samples from kidney transplant recipients undergoing allograft biopsy. CXCL9 and CXCL10 levels were measured by ELISA and the ratio to urine creatinine was calculated. Histology and other clinical data were collected from medical records.
RESULTS
The diagnostic performance of urinary CXCL9/cre in discriminating rejection from all other histological groups showed an ROC AUC value of 0.728 (95% CI 0.632-0.824, p<0.001), and a cut-off value 0.11 ng/mmol had the best sensitivity (76.9%) and specificity (73.1%). The ability of CXCL10/cre to discriminate transplant rejection from all other histological groups had ROC AUC value 0.73 (95% CI 0.63-0.84, P<0.001), the cut-off value 0.42 ng/mmol with best sensitivity (71.4%) and specificity (84.6%). CXCL9 and CXCL10 levels were also increased in patients with polyoma BK virus, recurrent AA amyloidosis, and thrombotic microangiopathy. Patients with higher CXCL9/cre (≥0.11 ng/mmol) and CXCL10/cre (≥0.42 ng/mmol) levels were at increased risk of transplant progression to ESRD (HR 3.25, 95% CI=1.27-8.36, P=0.01), irrespective of serum creatinine at the time of biopsy.
CONCLUSIONS
Urinary CXCL9/cre and CXCL10/cre were able to distinguished between patients with transplant rejection and those without rejection. High levels of urinary CXCL9/cre and CXCL10/cre were associated with worse allograft survival.
Keywords: Biomarkers; Chemokines, CXC; Graft Rejection; Kidney Transplantation
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