Early detection of allograft rejection is critical to the successful management of transplant recipients. Tissue biopsy has been the "gold standard" for diagnosis of active rejection (AR), but is invasive and has poor reproducibility. 1 Conventional noninvasive biomarkers, such as changes in serum creatinine, are available for detecting AR, but are limited due to low sensitivity and specificity. 2 Thus, there is a need for new noninvasive markers that have high accuracy for detecting AR.Donor-derived cell-free DNA fraction (dd-cfDNA[%]) is a promising noninvasive biomarker for detecting allograft rejection. However, dd-cfDNA(%) can be artificially depressed by high levels of circulating cfDNA, which can occur in patients who are obese, have had recent surgery, have medical complications, or received certain medications. 3 This can potentially lead to false negative results.Recently, two studies provided preliminary evidence indicating that the absolute quantity of dd-cfDNA may show better performance for detecting AR than dd-cfDNA(%). 4,5 In this study we present our results from an assay that utilizes a new two-threshold algorithm that combines both dd-cfDNA(%) and absolute quantity of dd-cfDNA (copies/ml), with the goal of increasing test sensitivity, particularly through improved detection in patients where cfDNA levels are high.

In 2017, United Network for Organ Sharing (UNOS) established the safety net policy with set criteria for offering kidney transplantation (KT) for patients who developed end-stage renal disease between 60 and 365 days after liver transplant (LT). We provide an update on the impact of the policy. We analyzed UNOS data of liver recipients transplanted between 1987 and 2020 who developed acute kidney injury requiring dialysis within 60 days before or after LT and subsequently listed for KT. We identified 407 patients who were listed for kidney after LT before policy and 248 patients after policy. Median waiting time to KT was shorter after policy (324 days vs. 2827 days). There was a higher proportion of candidates who were listed for subsequent KT within 1-year after policy (94.8% vs. 63.6%). KT rate was also higher after policy (87.7 vs. 30.7 per 100 patient-years at risk). Most importantly, we started to observe a net negative kidney utilization in end-stage liver disease setting (i.e., summation of simultaneous liver kidney and kidney after liver transplant in the first-year after LT has decreased from 1086 to 876 transplants in 2019). Such findings are consistent with a more efficient system and more appropriate allocation of organs.

Background: Under the current kidney allocation system, pediatric candidates listed prior to age 18 receive priority for high-quality deceased donor organs. This has resulted in a decline in living donor transplantation in pediatrics, despite superior outcomes of living donor transplantation. Due to a young age at transplantation, most pediatric kidney transplant recipients require re-transplantation. The effects of a previously failed deceased donor vs a previously failed living donor on re-transplant candidates are unknown. Methods: Using the United Network for Organ Sharing database, we examined 2772 re-transplant recipients aged 18-30 years at time of relisting for second KT from 2000 to 2018 with history of prior pediatric KT (age ≤ 18 years). Results: PFLDKT recipients compared to those with PFDDKT had shorter median waiting times and dialysis time regardless of their second donor type (14.0 vs 20.3 months, and 19.1 vs 34.5 months, respectively). PFLDKT recipients had higher re-transplant rates (adjusted HR 1.17, 95% CI 1.09-1.27, and adjusted HR 1.05, 95% CI 0.95-1.15 when calculating from time of relisting and time of returning to dialysis, respectively). PFDDKT recipients were more likely to have higher median PRA levels (90% vs 73%). Conclusions: Re-transplant candidates who received a previous deceased donor as a child had a higher level of sensitization, longer waiting time, and dialysis exposure compared to those with PFLDKT. Among primary pediatric kidney transplant candidates, consideration should be considered for living donor transplantation, despite the priority for deceased donor organs, to avoid increased sensitization and longer waiting times for with re-transplantation.