Using Both Plasma and Urine Donor-Derived Cell-Free DNA to Identify Various Renal Allograft Injuries.

ABSTRACT

BACKGROUND: This study was designed to investigate the association between donor-derived cell-free DNA (dd-cfDNA) and renal allograft injuries. METHODS: This single-center study enrolled 113 adult kidney transplant recipients with kidney biopsies. Plasma and urine dd-cfDNA was detected by target region capture sequencing. RESULTS: Plasma dd-cfDNA fraction was increased in multiple types of injuries, but most significantly in antibody-mediated rejection. Plasma dd-cfDNA fraction in isolated antibody-mediated rejection (1.94%, IQR 1.15%, 2.33%) was higher than in T cell-mediated rejection (0.55%, IQR 0.50%, 0.73%, P = 0.002) and negative biopsies (0.58%, IQR 0.42%, 0.78%, P < 0.001), but lower than in mixed rejection (2.49%, IQR 1.16%, 4.90%, P = 0.342). Increased urine dd-cfDNA concentration was associated with several types of injury, but most significantly with BK polyomavirus-associated nephropathy. Urine dd-cfDNA concentration in BK polyomavirus-associated nephropathy (12.22 ng/mL, IQR 6.53 ng/mL, 31.66 ng/mL) was respectively higher than that in T cell-mediated rejection (5.24 ng/mL, IQR 3.22 ng/mL, 6.99 ng/mL, P = 0.001), borderline change (3.93 ng/mL, IQR 2.45 ng/mL, 6.30 ng/mL, P < 0.001), and negative biopsies (3.09 ng/mL, IQR 1.94 ng/mL, 5.05 ng/mL, P < 0.001). Plasma dd-cfDNA fraction was positively associated with glomerulitis (r = 0.365, P < 0.001) and peri-tubular capillaritis (r = 0.344, P < 0.001), while urine dd-cfDNA concentration correlated with tubulitis (r = 0.302, P = 0.002). CONCLUSIONS: Both plasma and urine dd-cfDNA are sensitive markers for renal allograft injuries. The interpretation of a specific disease by dd-cfDNA should be combined with other clinical indicators.