*Purpose: Determine utility and efficacy of donor-derived cell free DNA (dd-cfDNA) monitoring in simultaneous kidney and pancreas (SPK) recipients compared to kidney transplant alone (KTA). DD-cfDNA testing is approved for non-invasive monitoring for allograft injury in KTA. DD-cfDNA testing has demonstrated strong negative predictive value for antibody mediated rejection (ABMR) in KTA. BK viremia in KTA is recognized to increase dd-cfDNA levels above baseline. It is unknown whether this assay has utility in SPK recipients based on higher potential cell turnover of multiple transplanted organs.

*Methods: SPK recipients were monitored prospectively after transplant with dd-cfDNA testing. Serial serum creatinine, amylase, and lipase were also measured in SPK recipients. This SPK cohort was compared to a coincident, prospective group of KTA recipients with a history of diabetes mellitus (DM).

*Results: Prospective dd-cfDNA was obtained in 12 SPK recipients and 14 KT recipients. All 12 SPK recipients had history of type 1 DM with mean age 40.4 (+/- 6.2) years at the time of transplant. There were 4 female (33.3%) recipients, 8 Caucasian (66.7%), 2 Asian (16.6%), 1 African American (8.3%) and 1 Hispanic (8.3%). The control group of 14 KTA recipients consisted of 9 (64.2%) patients with history of type 1 DM and 5 (35.7%) patients with type 2 DM. Mean age at the time of KT was 53.2 (+/-14.1) years. This cohort consisted of 9 (64.2%) females , 9 (64.2%) Caucasian and 5 (35.7%) African American recipients. All recipients had initial dd-cfDNA results under 1%. KTA recipients had mean dd-cfDNA 0.26 (mode <0.19) post KTA compared to mean SPK dd-cfDNA 0.34 (mode <0.19) after 70.2 ± 10.2 weeks post-transplant. DD-cfDNA peaked at 1.2% in 1 SPK recipient with BK viremia and normalized under 1% after resolution. All but one SPK recipient had functional kidney and pancreas grafts after 70.2 ± 10.2 weeks. In 1 SPK recipient who had pancreatic graft failure due to thrombosis, dd-cfDNA remained <0.19. A negative kidney biopsy for ABMR and no identifiable DSA confirmed absence of ABMR in this patient. One KTA patient experienced death with functional graft.

*Conclusions: SPK recipients maintain normal dd-cfDNA levels after successful transplantation. Similar to KTA, SPK recipients demonstrate increases in dd-cfDNA with BK viremia. Thus, prospective monitoring with dd-cfDNA has utility in SPK recipients. Further investigation with larger SPK cohorts is needed to validate dd-cfDNA utilization.

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