*Purpose: Donor derived-cell free DNA (dd-cfDNA) is a biomarker of immunological injury. Multiple studies have validated its utility in recipients of first solitary kidney transplants (s-KT) while its utility in regrafts with previous in-situ failed kidney transplants (r-KT) who conceivable have a second source of dd-cfDNA is not yet fully defined. Here we present our findings and comparison of values in patients with no rejection, any rejection or ABMR by both histology and molecular microscope.

*Methods: In our center all KT biopsies in addition to histological assessment also undergo dd-cfDNA (Allosure, CareDx) and molecular microscope (MMDx; ATAGC; Canada) analysis. We evaluated eighty-seven KT biopsies with no rejection, by histology and MMDx. Seventy-eight KT biopsies with evidence of any rejection by histology and MMDx. Finally, we evaluated fifty-three KT biopsies with evidence of only ABMR by both histology and MMDx.

*Results: KT biopsies with no rejection, seventy (70/87; 80%) biopsies were performed on s-KT and seventeen (17/87; 20%) were on r-KT. The main indication for biopsy in each group was surveillance (s-KT 30/70; 42% vs r-KT 12/17; 70%) followed by AKI (s-KT 22/70; 31% vs r-KT 4/17; 24%) The median dd-cfDNA in the r-KT group was 0.30% (IQR: 0.21-0.54) which was not different than 0.35% (IQR: 0.18-0.54) in the s-KT group (p=0.78). KT biopsies with any rejection on both platforms, fifty-one (51/78; 65%) of the biopsies were performed on s-KT and twenty-seven (27/78; 35%) were performed on r-KT. The major indication for biopsy in each group was surveillance (s-KT 30/51; 59% vs r-KT 22/27; 81%). The median dd-cfDNA in the r-KT group was 1.5% (IQR: 0.91-2.0) which was not different than 2.1% (IQR: 0.86-3.3) in the s-KT group (p=0.27). KT biopsies with only ABMR by both histology and MMDx, thirty-four (34/53; 64%) of the biopsies were performed on s-KT and nineteen (19/53; 36%) were on r-KT. The main indication for biopsy in each group was surveillance (s-KT 25/34; 74% vs r-KT 16/19; 84%) The median dd-cfDNA in the r-KT group was 1.5% (IQR: 0.86-2.0) which was not different than 2.0% (IQR: 0.86-3.6) in the s-KT group (p=0.57).

*Conclusions: Here we report that there is no difference in dd-cfDNA in recipients s-KT versus r-KT in the setting of no rejection, any rejection or isolated ABMR confirmed by both by histology and molecular signature. We were able to increase the precision of the diagnosis with addition of the molecular microscope analysis. We hypothesize that despite presence of a second source of dd-cfDNA, the lack of nephron mass in the failed allograft prevents it from being a clinically significant source of dd-cfDNA. Further studies will allow this noninvasive biomarker of allograft injury to be used in the ever growing regraft patient population that are commonly sensitized and hence subjected to invasive surveillance biopsies.

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