Repeat Donor‐Derived Cell‐Free DNA Monitoring for Adjunctive Assessment of BK Polyomavirus Nephropathy Clinical Courses

The clinical courses of BK polyomavirus nephropathy (BKPyVN) are variable. This study aimed to evaluate the usefulness of repeat donor-derived cell-free DNA (dd-cfDNA) monitoring in identifying clinical courses. Repeat allograft biopsy and dd-cfDNA monitoring were performed at 6-12 months post-intervention or when renal allograft dysfunction occurred. Results demonstrated that recipients with rejection had a higher plasma dd-cfDNA fraction (2.23% [1.17%, 5.52%]; n = 13) than those with resolved BKPyVN (0.80% [0.66%, 0.91%]; n = 30; p < 0.001) or persistent BKPyVN (0.82% [0.61%, 1.12%]; n = 10; p = 0.002). Compared to baseline at BKPyVN diagnosis, urine dd-cfDNA concentration decreased in recipients with resolved BKPyVN post-intervention (3.90 [1.35, 5.80] ng/mL vs. 7.88 [6.00, 15.37] ng/mL; p < 0.001), but not in persistent BKPyVN (9.02 [5.26, 10.35] ng/mL vs. 7.96 [6.43, 10.21] ng/mL; p = 0.463). Changes in urine dd-cfDNA concentration were positively correlated with changes in the extent of SV40 LTag-positive staining, while changes in plasma dd-cfDNA fraction positively correlated with changes in glomerulitis score. A plasma dd-cfDNA fraction > 1.12% following BKPyVN intervention could identify rejection (AUC = 0.924), and a urine dd-cfDNA concentration > 5.95 ng/mL could identify persistent BKPyVN (AUC = 0.840). In summary, repeat dd-cfDNA monitoring integrated with clinical data can serve as an adjunct to identify BKPyVN clinical courses.