Levels of donor-derived cell-free DNA and chemokines in BK polyomavirus-associated nephropathy.

Abstract

BK polyomavirus-associated nephropathy (BKPyVAN) carries a risk of irreversible allograft injury. While detection of BK viremia and biopsy assessment are the current diagnostic gold standard, the diagnostic value of biomarkers reflecting tissue injury (donor-derived cell-free DNA [dd-cfDNA]) or immune activation (C-X-C motif chemokine ligand [CXCL]9 and CXCL10) remains poorly defined. For this retrospective study, 19 cases ofBKPyVANwere selected from the Vienna transplant cohort (biopsies performed between 2012 and 2019). Eight patients with T cell-mediated rejection (TCMR), 17 with antibody-mediated rejection (ABMR) and 10 patients without polyomavirus nephropathy or rejection served as controls. Fractions of dd-cfDNAwere quantified using next-generation sequencing and CXCL9 and CXCL10 were detected using multiplex immunoassays. BKPyVANwas associated with a slight increase in dd-cfDNA(median; interquartile range: .38% [.27%-1.2%] vs. .21% [.12%-.34%] in non-rejecting control patients; p=.005). Levels were far lower than in ABMR (1.2% [.82%-2.5%]; p=.004]), but not different from TCMR (.54% [.26%-3.56%]; p=.52). Within theBKPyVANcohort, we found no relationship between dd-cfDNAlevels and the extent of tubulo-interstitial infiltrates,BKPyVANclass and BK viremia/viruria, respectively. In some contrast to dd-cfDNA, concentrations of urinary CXCL9 and CXCL10 exceeded those detected in ABMR, but similar increases were also found in TCMR. BKPyVANcan induce moderate increases in dd-cfDNAand concomitant high urinary excretion of chemokines, but this pattern may be indistinguishable from that of TCMR. Our results argue against a significant value of these biomarkers to reliably distinguishBKPyVANfrom rejection.