Elevated donor derived cell free DNA (ddcfDNA) has been shown to correlate with allograft rejection following heart, lung, and kidney transplantation. We investigated whether sequential ddcfDNA measurements following HLA incompatible transplantation correlated with donor specific HLA antibody (DSA) levels and antibody mediated injury.

All recipients experienced DSA increases within two weeks post-transplant. Quantitation of ddcfDNA was performed via next generation sequencing and normalized to total recipient derived cell free DNA. Pre-transplant DNA samples were used to confirm informative variants at 202 polymorphic regions. 85 sequential plasma samples obtained prior to and immediately following transplantation for 8 recipients were analyzed. ddcfDNA and DSA were correlated to serum creatinine (SCr), microvascular injury (glomerulitis + peritubular capillaritis >3), and C4d staining. A positive threshold of 1% ddcfDNA was used in this analysis.

All 8 cases had a rise in %ddcfDNA (mean 2.7%) that was concordant with the rise in DSA. ddcfDNA levels >1% occurred in 7 cases and 0.9% in one case. Detection of elevated ddcfDNA levels occurred within 5 days after the DSA rise. Biopsies examined were performed within 1-22 days (mean 12 days) of the observed elevation in ddcfDNA. Six biopsies showed microvascular injury and positive C4d staining. The remaining 2 biopsies (one corresponding to 0.9% ddcfDNA elevation) showed mild glomerulitis with no other evidence of injury. SCr levels were less informative in determining active antibody injury during this early post-transplant period. Four recipients displayed normal SCr levels (1-1.5 mg/dL) at time of ddcfDNA elevation including 2 with histological evidence of injury on biopsy. Three of the remaining 4 recipients exhibited a stall in SCr decline (2-3 mg/dL) post-transplantation; 3 of whom were transplanted with deceased donor kidneys making it difficult to discern between delayed function and active antibody mediated rejection.

Elevated ddcfDNA correlated with a concomitant DSA increase in all cases and elevation beyond a 1% threshold correlated with antibody mediated injury in 6 of 7 cases. Sequential ddcfDNA testing in this DSA positive transplant cohort provided useful data for monitoring allograft injury and may prove more precise than SCr levels.

CITATION INFORMATION: Jackson A., Iglehart B., Bagnasco S., Desai N. Molecular Monitoring for Kidney Allograft Injury Following HLA Incompatible Transplantation Am J Transplant. 2017;17 (suppl 3).

« Back to 2018 American Transplant Congress