Levels of donor-derived cell-free DNA and chemokines in BK polyomavirus-associated nephropathy.
Clin Transplant
; 36(11): e14785, 2022 11.
Article
in En
| MEDLINE
| ID: mdl-35894263
ABSTRACT
BACKGROUND:
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.METHODS:
For this retrospective study, 19 cases of BKPyVAN were 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-cfDNA were quantified using next-generation sequencing and CXCL9 and CXCL10 were detected using multiplex immunoassays.RESULTS:
BKPyVAN was 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 the BKPyVAN cohort, we found no relationship between dd-cfDNA levels and the extent of tubulo-interstitial infiltrates, BKPyVAN class 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.CONCLUSION:
BKPyVAN can induce moderate increases in dd-cfDNA and 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 distinguish BKPyVAN from rejection.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Kidney Transplantation
/
BK Virus
/
Polyomavirus Infections
/
Cell-Free Nucleic Acids
/
Kidney Diseases
Type of study:
Observational_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Clin Transplant
Journal subject:
TRANSPLANTE
Year:
2022
Document type:
Article
Affiliation country: