Urinary C-X-C Motif Chemokine 10 Is Related to Acute Graft Lesions Secondary to T Cell- and Antibody-Mediated Damage

BACKGROUND: Non-invasive biomarkers of graft rejection are needed to optimize the management and outcomes of kidney transplant recipients. Urinary excretion of IFN-γ-related chemokine CXCL10 is clearly associated with clinical and subclinical T cell-mediated graft inflammation, but its relationship with antibody-mediated damage has not been fully addressed. Further, the variables influencing levels of urinary CXCL10 excretion are unknown. MATERIAL/METHODS: A total of 151 kidney graft biopsies (92 surveillance and 59 indication biopsies) and 151 matched urine samples obtained before biopsy were prospectively analyzed. T cell-mediated rejection (TCMR) and antibody-mediated rejection (AbMR) were defined according to the 2017 Banff classification criteria. Urinary CXCL10 levels were measured by ELISA and corrected by urinary creatinine. RESULTS: Banff scores ‘t’, ‘i’, ‘g’, and ‘ptc’ were significantly related to urinary CXCL10 levels. Multivariate analysis showed that ‘t’ (β=0.107, P=0.001) and ‘ptc’ (β=0.093, P=0.002) were significantly associated with urinary CXCL10. Donor-specific antibodies (DSAs) were related to the high excretion of urinary CXCL10 at 1 year after transplantation (odds ratio [OR] 17.817, P=0.003). Urinary CXCL10 showed good discrimination ability for AbMR (AUC-ROC 0.760, P=0.001). The third tertile of urinary CXCL10 remained significantly associated with AbMR (OR 4.577, 95% confidence interval 1.799–11.646, P=0.001) after multivariate regression analysis. CONCLUSIONS: DSA was the only variable clearly related to high urinary CXCL10 levels. Urinary CXCL10 is a good non-invasive candidate biomarker of AbMR and TCMR, supplying information independent of renal function and other variables normally used to monitor kidney transplants.