Using Both Plasma and Urine Donor-Derived Cell-Free DNA to Identify Various Renal Allograft Injuries.
Clin Chem
; 68(6): 814-825, 2022 06 01.
Article
in En
| MEDLINE
| ID: mdl-35587713
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 (12.22â ng/mL, IQR 6.53â ng/mL, 31.66â ng/mL) was respectively higher than that in T cell-mediated rejection (5.24â ng/mL, IQR 3.22â ng/mL, 6.99 ng/mL, P = 0.001), borderline change (3.93â ng/mL, IQR 2.45â ng/mL, 6.30â ng/mL, P < 0.001), and negative biopsies (3.09â ng/mL, IQR 1.94â ng/mL, 5.05â 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Kidney Transplantation
/
Cell-Free Nucleic Acids
/
Graft Rejection
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Adult
/
Humans
Language:
En
Journal:
Clin Chem
Journal subject:
QUIMICA CLINICA
Year:
2022
Document type:
Article