Diagnostic Potential of Urine CXCL10 and Donor-Derived cfDNA in Kidney Transplant Rejection

Data suggests donor-derived cell-free DNA (dd-cfDNA) and urine CXCL10 outperform serum creatinine as a biomarker of antibody-mediated rejection (AMR) and T cell-mediated rejection (TCMR). We hypothesized that combining these biomarkers would improve the overall detection of rejection. We performed a retrospective two-center, case-controlled study of 103 adult renal transplant recipients who had for-cause or surveillance biopsies with corresponding urine and plasma samples. Rejection was classified by Banff 2022 criteria. While log 10 %dd-cfDNA correlated more strongly than log 10 CXCL10 with glomerulitis (r = 0.55, p < 0.001 vs. r = 0.25, p = 0.01) and peritubular capillaritis (r = 0.47, p < 0.001 vs. r = 0.23, p = 0.02), log 10 CXCL10 was a better correlate of tubulitis (r = 0.28, p = 0.004 vs. r = 0.054, p = 0.59). Both dd-cfDNA > 0.5% (OR 21.9, 95% CI 3.74–180, p < 0.001) and de novo DSA (OR 10.4, 95% CI 1.16–157, p = 0.037) were independently associated with AMR vs. no rejection (NR), while log 10 serum creatinine and log 10 CXCL10 were not (p > 0.05). While dd-cfDNA >0.5% (OR 5.37, 95% CI 1.04–31.5, p = 0.047) was independently associated with Banff ≥1A TCMR vs. NR, log 10 CXCL10 was a significant predictor of TCMR in a model without %dd-cfDNA (OR 3.12, 95% CI 1.09–10.4, p = 0.043). Biomarker-guided screening strategies based on dd-cfDNA and urine chemokines such as CXCL10 for AMR (microvascular injury) and TCMR (tubulitis) warrant further study.