Early Experience Using Donor-derived Cell-free DNA for Surveillance of Rejection Following Simultaneous Pancreas and Kidney Transplantation

Abstract

Background. Allograft biopsy is the gold standard for diagnosing graft rejection following simultaneous pancreas and kidney (SPK) transplant. Intraperitoneal biopsies are technically challenging and can be burdensome to patients and the healthcare system. Donor-derived cell-free DNA (dd-cfDNA) is well-studied in kidney transplant recipients; however, it has not yet been studied in the SPK population. Methods. We hypothesized that dd-cfDNA could be utilized for rejection surveillance following SPK transplant. We prospectively collected dd-cfDNA in 46 SPK patients at a single institution. Results. There were 10 rejection events, 5 of which were confirmed with biopsy. The other 5 were treated based on dd-cfDNA and clinical data alone with favorable outcomes. Among all patients who did not have rejection, 97% had dd-cfDNA <0.5%. Dd-cfDNA may also help differentiate rejection from graft injury (ie, pancreatitis) with median values in rejection 2.25%, injury 0.36%, and quiescence 0.18% (P = 0.0006). Conclusions. Similar to kidneys, dd-cfDNA shows promise for rejection surveillance in SPK transplant recipients.

An Initial Analysis of the Baseline Levels of Dd-cfDNA After Pancreas Transplantation: A Prospective Study From High-volume Centers in the United States

“…This finding is consistent with published case-by-case evidence that dd-cfDNA sheds differently in the setting of graft injury due to rejection versus inflammation. 33 Our findings also revealed how dd-cfDNA values seem slightly higher in bacterial versus viral infections, although our limited sample size per infectious cause warrants further study of specific etiologies. Although more analysis is required to verify validity of dd-cfDNA in rejection and infection, these results do reflect a difference in dd-cfDNA response in the setting of pancreas graft dysfunction and thus support utility of dd-cfDNA in graft surveillance.…”

“…Furthermore, median values for rejection in SPK transplantation in this study are consistent with published literature (0.19%) and agree with these findings. 33,36,37 However, this study also has several limitations. One limitation is the paucity of biopsy confirmed rejections.…”

“…Furthermore, median values for rejection in SPK transplantation in this study are consistent with published literature (0.19%) and agree with these findings. 33,36,37…”

Different biopsy techniques for different pancreas graft locations after homolateral simultaneous pancreas-kidney transplantation

“…Biopsy of the transplanted pancreas has been difficult to perform in clinical practice ( 8 , 9 ). Compared with that of renal graft biopsy, the vascular distribution of the transplanted pancreas is complicated, and the pancreas is surrounded by the adherent recipient intestine.…”

Free-Circulating Nucleic Acids as Biomarkers in Patients After Solid Organ Transplantation

“…There are a few published studies regarding using cell-free DNA in pancreas/kidney transplant recipients (SPKT). Gadi et al found that detection of cfDNA was high in the first month after pancreas transplantation, with a rapid decline thereafter, and with increased correlation with biopsy-proven acute allograft rejection [ 24 ]. In another study, Williams et al [ 25 ] found that levels of circulating donor cell-free DNA are significantly lower in stable recipients and even those with pancreatitis compared to patients who experienced acute rejection.…”