A rapid noninvasive assay for the detection of renal transplant injury

Transplantation. 2013 Jul 15;96(1):97-101. doi: 10.1097/TP.0b013e318295ee5a.


Background: The copy number of donor-derived cell-free DNA (dd-cfDNA) in blood correlates with acute rejection (AR) in heart transplantation. We analyzed urinary dd-cfDNA as a surrogate marker of kidney transplant injury.

Methods: Sixty-three biopsy-matched urine samples (41 stable and 22 allograft injury) were analyzed from female recipients of male donors for chromosome Y (donor)-specific dd-cfDNA. All biopsies were semiquantitatively scored by a single pathologist. Standard statistical measures of correlation and significance were used.

Results: There was baseline scatter for urinary dd-cfDNA/μg urine creatinine across different patients, even at the time of stable graft (STA) function (undetected to 12.26 copies). The mean urinary dd-cfDNA in AR (20.5 ± 13.9) was significantly greater compared with STA (2.4 ± 3.3; P<0.0001) or those with chronic allograft injury (CAI; 2.4 ± 2.4; P=0.001) but no different from BK virus nephropathy (BKVN; 20.3±15.7; P=0.98). In AR and BKVN, the intrapatient drift was highly significant versus STA or CAI patients (10.3 ± 7.4 in AR; 12.3 ± 8.4 in BKVN vs. -0.5 ± 3.5 in STA and 2.3 ± 2.6 in CAI; P<0.05). Urinary dd-cfDNA correlated with protein/creatinine ratio (r=0.48; P<0.014) and calculated glomerular filtration rate (r=-0.52; P<0.007) but was most sensitive for acute allograft injury (area under the curve=0.80; P<0.0006; 95% confidence interval, 0.67-0.93).

Conclusion: Urinary dd-cfDNA after renal transplantation has patient specific thresholds, reflecting the apoptotic injury load of the donor organ. Serial monitoring of urinary dd-cfDNA can be a surrogate sensitive biomarker of acute injury in the donor organ but lacks the specificity to distinguish between AR and BKVN injury.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Apoptosis
  • BK Virus / genetics
  • Biomarkers / blood
  • Biomarkers / urine
  • Child
  • Chromosomes, Human, Y*
  • DNA / blood
  • DNA Copy Number Variations
  • Female
  • Graft Rejection / diagnosis*
  • Graft Rejection / drug therapy
  • Graft Rejection / metabolism
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Kidney Transplantation / adverse effects*
  • Male
  • Polyomavirus Infections / diagnosis
  • Reperfusion Injury / diagnosis*
  • Reperfusion Injury / metabolism
  • Sensitivity and Specificity
  • Sex Factors
  • Transplantation, Homologous
  • Tumor Virus Infections / diagnosis
  • Young Adult


  • Biomarkers
  • Immunosuppressive Agents
  • DNA