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A Rapid Noninvasive Assay for the Detection of Renal Transplant Injury

Sigdel, T.K., Vitalone, M.J., Tran, T.Q., Dai, H., Hsieh, S.C., Salvatierra, O., Sarwal, M.M.

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.

Citation

Sigdel, T.K., Vitalone, M.J., Tran, T.Q., Dai, H., Hsieh, S.C., Salvatierra, O., Sarwal, M.M. "A Rapid Noninvasive Assay for the Detection of Renal Transplant Injury" Transplantation (2013): 97–101