Outcomes of Kidney Perfusion Techniques in Transplantation from Deceased Donors: A Systematic Review and Meta-Analysis.

The high demand for organs in kidney transplantation and the expansion of the donor pool have led to the widespread implementation of machine perfusion technologies. In this study, we aim to provide an up-to-date systematic review of the developments in this expanding field over the past 10 years, with the aim of answering the question: "which perfusion technique is the most promising technique in kidney transplantation?" A systematic review of the literature related to machine perfusion in kidney transplantation was performed. The primary outcome measure was delayed graft function (DGF), and secondary outcomes included rates of rejection, graft survival, and patient survival rates after 1 year. Based on the available data, a meta-analysis was performed. The results were compared with data from static cold storage, which is still the standard of care in many centers worldwide. A total of 56 studies conducted in humans were included, and 43 studies reported outcomes of hypothermic machine perfusion (HMP), with a DGF rate of 26.4%. A meta-analysis of 16 studies showed significantly lower DGF rates in the HMP group compared to those of static cold storage (SCS). Five studies reported outcomes of hypothermic machine perfusion + O2, with an overall DGF rate of 29.7%. Two studies explored normothermic machine perfusion (NMP). These were pilot studies, designed to assess the feasibility of this perfusion approach in the clinical setting. Six studies reported outcomes of normothermic regional perfusion (NRP). The overall incidence of DGF was 71.5%, as it was primarily used in uncontrolled DCD (Maastricht category I-II). Three studies comparing NRP to in situ cold perfusion showed a significantly lower rate of DGF with NRP. The systematic review and meta-analysis provide evidence that dynamic preservation strategies can improve outcomes following kidney transplantation. More recent approaches such as normothermic machine perfusion and hypothermic machine perfusion + O2 do show promising results but need further results from the clinical setting. This study shows that the implementation of perfusion strategies could play an important role in safely expanding the donor pool.

Real-time assessment of kidney allografts during HOPE using flavin mononucleotide (FMN) - a preclinical study.

Introduction: The gap between available donor grafts and patients on the waiting lists is constantly growing. This leads to an increased utilization of high-risk and therefore more vulnerable kidney grafts. The use of high-risk organs requires further optimization of machine preservation and assessment strategies before transplantation. Hypothermic machine perfusion (HMP) is the standard of care for kidneys originating from donation after circulatory death (DCD), whereas the evidence of HMP with additional oxygen (HOPE) is still very limited. Furthermore, an objective quality assessment of HMP-perfused kidneys is lacking. Recently, the release of mitochondria derived fragments, i.e., flavin mononucleotide (FMN) of complex I during machine liver perfusion was shown to be predictive for liver graft function before implantation. Therefore, the aim of this study was to evaluate, if FMN is useful also for assessment of kidney injury before use. Methods: A porcine perfusion model was used to investigate the feasibility of assessment of kidney grafts during hypothermic oxygenated perfusion (HOPE) with either 0, 30 or 60 minutes of warm ischemia. The model with warm ischemia times (WIT) of 30 min and 60 min, was used to mimic a clinically relevant scenario. A group with no warm ischemia time (0' WIT) served as control group. The groups underwent minimal static cold storage (SCS) of 2 h followed by 2 h of end-ischemic HOPE with repeated real-time FMN measurements. In a further step, these values were related to the release of damage-associated molecular patterns (DAMPs) and to the functionality of the respiratory chain, represented by the capacity of ATP production. Results: We demonstrate, first, feasibility of perfusate FMN measurements in perfused kidneys, and secondly its correlation with donor warm ischemia time. Accordingly, FMN measurement showed significantly higher release in the 60-minute WIT group (n = 4) compared to the 30-minute WIT (n = 4) and the control group (n = 4). FMN release correlated also with DAMP signaling, such as the release of 8-OHdG and HMGB1. Finally, ATP replenishment proved to be best in control kidneys, followed by kidneys with 30 min and then by kidneys with 60 min of WIT. Discussion: This study demonstrates the feasibility of FMN measurement in kidneys during HOPE. In addition, we show a correlation between FMN quantification and pre-existing kidney graft injury. Based on this, real-time FMN measurement during HOPE may be an objective assessment tool to accept high-risk kidneys for transplantation while minimizing post-transplant dysfunction, moving away from former "gut feeling" towards objective criteria in accepting marginal kidney grafts for transplantation. Graft evaluation based on these results may close the gap between available grafts and patients on the waiting lists by increasing utilization rates without significant impact for the recipients.

High risk of septic complications following surgery for Crohn's disease in patients with preoperative anaemia, hypoalbuminemia and high CRP.

AIM: Bowel resection in Crohn's disease still has a high rate of complications due to risk factors including immune suppression, malnutrition and active inflammation or infection at the time of operating. In this study, we use serological levels and inflammatory markers to predict the potential of complications in patients undergoing resections for complicated Crohn's disease. METHODS: All patients undergoing laparoscopic bowel resection for Crohn's disease from 5th of November 2012 to 11th of October 2017 were included in this retrospective observational study. Patients were divided into 4 groups scoring 0, 1, 2 or 3 depending on their pre-operative haemoglobin concentration (Hb), C-reactive protein (CRP) and albumin (Alb) where 1 point was given for an abnormal value in each as detailed in the definitions. They were then grouped into a low risk group comprised of those scoring 0 and 1, and a high risk group for those scoring 2 and 3 and data was collected to compare outcomes and the incidence of septic complications. RESULTS: Seventy-nine patients were included. Eleven (13.9%) and 2 (2.5%) patients had 2 or 3 abnormal values of CRP, Alb and Hb and were categorized as high risk. High risk patients had a significantly higher rate of post-operative septic complications (30.7%) compared with low risk patients (10.6%) p value < 0.0001. CONCLUSION: Pre-operative CRP, haemoglobin and albumin can serve as predictors of septic complications after surgery for Crohn's disease and can therefore be used to guide pre-operative optimisation and clinical decision-making.