A rapid noninvasive assay for the detection of renal transplant injury

TK Sigdel, MJ Vitalone, TQ Tran, H Dai, S Hsieh… - …, 2013 - journals.lww.com
TK Sigdel, MJ Vitalone, TQ Tran, H Dai, S Hsieh, O Salvatierra, MM Sarwal
Transplantation, 2013journals.lww.com
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 …
Abstract
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.
Lippincott Williams & Wilkins