Background.: Normothermic machine perfusion (NMP) protocols using blood-based solutions are commonly used in the assessment of kidneys before transplantation. This procedure is, nevertheless, limited by blood availability and warrants the search for alternatives. We compared a blood-based solution with a serum-like preservation solution (Aqix) enriched with colloids with and without red blood cells (RBCs). Methods.: Porcine kidneys retrieved from an abattoir were subjected to 30 min of warm ischemia, followed by 3 h of hypothermic oxygenated machine perfusion at 4 °C. Subsequently, kidneys (n = 6 per group) were evaluated with NMP for 4 h with 5 different solutions: diluted blood, Aqix with BSA ± RBCs, or Aqix with dextran 40 ± RBCs. Results.: Throughout NMP, markers of renal function and tubular metabolism were favorable in groups with RBCs. The addition of RBCs resulted in 4- to 6-fold higher oxygen consumption rates. Controls had significantly higher ATP levels post-NMP, exhibited decreased production of oxidative stress markers, and had the highest creatinine clearance. In conclusion, this study shows that the addition of RBCs during NMP reduced renal injury, improved function, and was associated with increased renal metabolism. Conclusions.: Although the RBC-BSA–supplemented Aqix solution was also able to support metabolism and renal function, a blood-based perfusion solution remains superior.

Background: Organ shortage remains a major challenge for the field of transplantation. Maximizing utilization and minimizing discard of available organs is crucial to reduce waitlist times. Our aim was to investigate the landscape of liver recovery, discard over the past decade in the United States, and identify areas to reduce organ discard. Methods: This study used the Scientific Registry of Transplant Recipients United Network for Organ Sharing database to analyze the rates and associated reasons of discarded organs from 2010 to 2021. All deceased donors were evaluated, and data were analyzed by organ type, year, and region. Organ disposition was analyzed by year and region. Donor demographics and liver biopsy data were also analyzed. Results: The volume of liver transplantation increased steadily, with a 44% increase from 2010 to 2021. Donation after circulatory death transplantation increased by 239%, comprising 10.6% of transplants in 2021, yet discard rates remained high at 30% for this donor subset. For all donor types, the liver discard rate has remained stable around 10% despite a 74% increase in available donors. Seventy percent of liver discards were attributed to organ factors, with biopsy findings accounting for 40% of all discards. Of livers that were biopsied, 70% had macrosteatosis of <30%. Conclusions: Analysis of trends in transplantation and discard allow for identifying areas of underutilization. Donation after circulatory death livers have expanded the pool of transplanted livers but remain discarded at high rates. Significant differences remain in discard rates between geographic regions. We identify several areas to lower the discard rates. The expanding role of machine perfusion may allow for utilization of previously discarded organs.

Assessment of donor kidney quality is based on clinical scores or requires biopsies for histological assessment. Noninvasive strategies to identify and predict graft outcome at an early stage are, therefore, needed. We evaluated the perfusate of donation after brain death (DBD) kidneys during nonoxygenated hypothermic machine perfusion (HMP). In particular, we compared perfusate protein profiles of good outcome (GO) and suboptimal outcome (SO) 1-year post-transplantation. Samples taken 15 min after the start HMP (T1) and before the termination of HMP (T2) were analysed using quantitative liquid chromatography–tandem mass spectrometry (LC-MS/MS). Hierarchical clustering of the 100 most abundant proteins showed discrimination between grafts with a GO and SO at T1. Elevated levels of proteins involved in classical complement cascades at both T1 and T2 and a reduced abundance of lipid metabolism at T1 and of cytoskeletal proteins at T2 in GO versus SO was observed. ATP-citrate synthase and fatty acid-binding protein 5 (T1) and immunoglobulin heavy variable 2-26 and desmoplakin (T2) showed 91% and 86% predictive values, respectively, for transplant outcome. Taken together, DBD kidney HMP perfusate profiles can distinguish between outcome 1-year post-transplantation. Furthermore, it provides insights into mechanisms that could play a role in post-transplant outcomes.

Kidney transplantation is a life-saving intervention for end-stage renal disease; yet, the persistent gap between organ demand and supply remains a significant challenge. This paper explores the escalating discard rates of deceased donor kidneys in the United States to assess trends, discard reasons, demographical differences, and preservation techniques. Data from the Scientific Registry of Transplant Recipients from 2010 to 2021 was analyzed using chi-squared tests for trend significance and logistic regression to estimate odds ratios for kidney discard. Over the last decade, discard rates have risen to 25% in 2021. Most discarded kidneys came from extended criteria donor (ECD) donors and elevated kidney donor profile index (KDPI) scores. Kidney biopsy status was a significant factor and predictor of discard. Discard rates varied greatly between Organ Procurement and Transplantation Network regions. Of reasons for discard, “no recipient located” reached a high of 60%. Additionally, there has been a twofold increase in hypothermic machine perfusion (HMP) since 2010, with transportation difficulties being the main reason for the discard of perfused kidneys. Our findings suggest a need to recalibrate organ utilization strategies, optimize the use of lower-quality kidneys through advanced preservation methods, and address the evolving landscape of organ allocation policies to reduce kidney discard rates.

Background and Purpose: Fibrosis in kidney allografts is a major post‐transplant complication that contributes to graft failure. Lately, multiple potent inhibitors of fibrosis‐related pathways have been developed such as galunisertib, an inhibitor of the transforming growth factor‐beta (TGF‐β/TGFβ1) signalling pathway. This drug, however, poses risks for adverse effects when administered systemically. Therefore, we devised a new repurposing strategy in which galunisertib is administered ex vivo. We combined machine perfusion and tissue slices to explore the antifibrotic effects of galunisertib in renal grafts.Experimental Approach: Porcine kidneys were subjected to 30 min of warm ischaemia, 24 h of oxygenated hypothermic machine perfusion and 6 h of normothermic machine perfusion with various treatments (i.e. untreated control, TGFβ1, galunisertib or TGFβ1 + galunisertib; n = 8 kidneys per group). To determine whether effects persisted upon ceasing treatment, kidney slices were prepared from respective kidneys and incubated for 48 h.Key Results: Galunisertib treatment improved general viability without negatively affecting renal function or elevating levels of injury markers or by‐products of oxidative stress during perfusion. Galunisertib also reduced inflammation and, more importantly, reduced the onset of fibrosis after 48 h of incubation.Conclusions and Implications: Our findings demonstrate the value of using machine perfusion for administering antifibrotic drugs such as galunisertib, proving it to be an effective example of repurposing.