Individual and Combined Impact of Oxygen and Oxygen Transporter Supplementation during Kidney Machine Preservation in a Porcine Preclinical Kidney Transplantation Model

Marginal kidney graft preservation in machine perfusion (MP) is well-established. However, this method requires improvement in order to mitigate oxidative stress during ischemia-reperfusion, by using oxygenation or an O2 carrier with anti-oxidant capacities (hemoglobin of the marine worm; M101). In our preclinical porcine (pig related) model, kidneys were submitted to 1h-warm ischemia, followed by 23 h hypothermic preservation in Waves® MP before auto-transplantation. Four groups were studied: W (MP without 100%-O2), W-O2 (MP with 100%-O2; also called hyperoxia), W-M101 (MP without 100%-O2 + M101 2 g/L), W-O2 + M101 (MP with 100%-O2 + M101 2 g/L) (n = 6/group). Results: Kidneys preserved in the W-M101 group showed lower resistance, compared to our W group. During the first week post-transplantation, W-O2 and W-M101 groups showed a lower blood creatinine and better glomerular filtration rate. KIM-1 and IL-18 blood levels were lower in the W-M101 group, while blood levels of AST and NGAL were lower in groups with 100% O2. Three months after transplantation, fractional excretion of sodium and the proteinuria/creatinuria ratio remained higher in the W group, creatininemia was lower in the W-M101 group, and kidney fibrosis was lower in M101 groups. We concluded that supplementation with M101 associated with or without 100% O2 improved the Waves® MP effect upon kidney recovery and late graft outcome

Characterization and effects of porcine adipose tissue mesenchymal stem cells on kidney graft recovery in a preclinical porcine model of renal transplantation

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Preventing acute kidney injury during transplantation: the application of novel oxygen carriers

International audienceIntroduction: Delayed graft function (DGF) has a significant impact on kidney transplantation outcome. One of the underlying pivotal mechanisms is organ preservation and associated hypothermia and biochemical alteration. Area covered: This paper focuses on organ preservation and its clinical consequences and describes 1. A comprehensive presentation of the pathophysiological mechanism involved in delayed graft function development; 2. The impact on endothelial cells and microvasculature integrity and the consequences on transplanted organ outcome; 3. The reassessment of dynamic organ preservation motivated by the growing use of extended criteria donors and the interest in the potential of normothermia; 4. The role of oxygenation during dynamic preservation; and 5. Novel oxygen carriers and their proof of concept in transplantation, among which M101 (HEMO(2)life (R)) is currently the most extensively investigated. Expert opinion: Metabolic disturbances and imbalance of oxygen supply during preservation highlight the importance of providing oxygen. Normothermia, permitted by recent advances in machine perfusion technology, appears to be the leading edge of preservation technology. Several oxygen transporters are compatible with normothermia; however, only M101 also demonstrates compatibility with standard hypothermic preservation

Vectisol Formulation Enhances Solubility of Resveratrol and Brings Its Benefits to Kidney Transplantation in a Preclinical Porcine Model

Current organ shortages have led centers to extend the acceptance criteria for organs, increasing the risk for adverse outcomes. Current preservation protocols have not been adapted so as to efficiently protect these organs. Herein, we target oxidative stress, the key mechanism of ischemia reperfusion injury. Vectisol® is a novel antioxidant strategy based on the encapsulation of resveratrol into a cyclodextrin, increasing its bioavailability. We tested this compound as an additive to the most popular static preservation solutions and machine perfusion (LifePort) in a preclinical pig model of kidney autotransplantation. In regard to static preservation, supplementation improved glomerular filtration and proximal tubular function early recovery. Extended follow-up confirmed the higher level of protection, slowing chronic loss of function (creatininemia and proteinuria) and the onset of histological lesions. Regarding machine perfusion, the use of Vectisol® decreased oxidative stress and apoptosis at the onset of reperfusion (30 min post declamping). Improved quality was confirmed with decreased early levels of circulating SOD (Superoxide Dismutase) and ASAT (asparagine amino transferase). Supplementation slowed the onset of chronic loss of function, as well as interstitial fibrosis and tubular atrophy. The simple addition of Vectisol® to the preservation solution significantly improved the performance of organ preservation, with long-term effects on the outcome. This strategy is thus a key player for future multi-drug therapy aimed at ischemia reperfusion in transplantation

Hypothermic pulsatile preservation of kidneys from uncontrolled deceased donors after cardiac arrest - a retrospective study

International audienceKidneys from uncontrolled donors after cardiac arrest (uDCD) suffer from a period of warm ischemia between cardiac arrest and cold flushing. Aim of the study was to evaluate renal outcomes of uDCD kidneys selected on the basis of renal Resistance Index (RI) and its influence on graft function and survival. The study included 44 kidneys procured from 26 uDCD starting 1.1.2006 until 12.31.2013. The donors (Maastricht category II) underwent cardiopulmonary resuscitation by assisted ventilation and chest compression; the organs were preserved with in situ cold perfusion or a normothermic regional perfusion. All kidneys were perfused on hypothermic (1-4 °C) pulsatile perfusion machine (RM3; Waters Medical System) and discarded when RI >=0.5 mmHg/ml/min after 6 h of perfusion. There was one (2.2%) primary non function, while 37 recipients (84.1%) experienced delayed graft function. Graft survival was 97.6% at 1 and 3 post-transplantation years. Linear regression models showed that lower values of RI at the end of perfusion were associated with higher values of Modification of Diet in Renal Disease at 3 (P = 0.049) and 6 months after transplantation (P = 0.010) and with higher values of inulin clearance at 1 year (P = 0.030). RI showed to be a useful tool to select uDCD kidneys allowing to achieve good clinical results

Early discharge in selected patients with low-grade renal trauma

International audienceIntroduction: the aim of this study was to assess whether early discharge could be non-inferior to inpatient management in selected patients with low-grade renal trauma (AAST grades 1–3).Materials and methods: A retrospective national multicenter study was conducted including all patients who presented with renal trauma at 17 hospitals between 2005 and 2015. Exclusion criteria were iatrogenic and AAST grades 4 and 5 trauma, non-conservative initial management, Hb  48 h (inpatient). The primary outcome was “Intervention” defined as any interventional procedure needed within the first 30 days. A Stabilized Inverse Probability of Treatment Weighting (SIPTW) propensity score based binary response model was used to estimate risk difference.Results: Out of 1764 patients with renal trauma, 311 were included in the analysis (44 in the early discharge and 267 in the inpatient group). In the early discharge group, only one patient required an intervention within the first 30 days vs. 10 in the inpatient group (3.7% vs. 5.2%; p = 0.99). Adjusted analysis using SIPTW propensity score showed a risk difference of − 2.8% [− 9.3% to + 3.7%] of “interventions” between the two groups meeting the non-inferiority criteria.Conclusion: In a highly selected cohort, early discharge management of low-grade renal trauma was not associated with an increased risk of early “intervention” compared to inpatient management. Further prospective randomized controlled trials are needed to confirm these findings

The Mayo Adhesive Probability score can help predict intra- and postoperative complications in patients undergoing laparoscopic donor nephrectomy

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