IL-1 receptor antagonist anakinra downregulates inflammatory cytokines during renal normothermic machine perfusion: Preliminary results.

Background: The interleukin 1 (IL-1) cytokine group plays a key role in sterile inflammation and may be an important target for transplant-related renal injury. This study examined the effects of anakinra, a non-specific IL-1 receptor antagonist, administered during normothermic machine perfusion (NMP) of porcine kidneys.

Method: Paired porcine kidneys (n = 5 pairs) underwent 15 min of warm ischemia plus 2 h of static cold storage in ice.

Current Basic Research in Normothermic Machine Perfusion.

Background: Normothermic machine perfusion (NMP) is gradually being introduced into clinical transplantation to improve the quality of organs and increase utilisation. This review details current understanding of the underlying mechanistic effects of NMP in the heart, lung, liver, and kidney. It also considers recent advancements to extend the perfusion interval in these organs and the use of NMP to introduce novel therapeutic interventions, with a focus on organ modulation.

Contrast-enhanced computed tomography for ex vivo assessment of human kidneys: A proof-of-concept study.

Background: Ex vivo perfusion of transplant-declined human organs has emerged as a promising platform to study the response of an organ to novel therapeutic strategies. However, to fully realize the capability of this platform for performing translational research in human organ pathophysiology, there is a need for robust assays to assess organ function and disease. State-of-the-art research methods rely on analyses of biopsies taken during perfusion, which both damages the organ and only provides localized information.

Enzymatic conversion of human blood group A kidneys to universal blood group O.

ABO blood group compatibility restrictions present the first barrier to donor-recipient matching in kidney transplantation. Here, we present the use of two enzymes, FpGalNAc deacetylase and FpGalactosaminidase, from the bacterium Flavonifractor plautii to enzymatically convert blood group A antigens from the renal vasculature of human kidneys to 'universal' O-type. Using normothermic machine perfusion (NMP) and hypothermic machine perfusion (HMP) strategies, we demonstrate blood group A antigen loss of approximately 80% in as little as 2 h NMP and HMP.

Normothermic machine perfusion versus static cold storage in donation after circulatory death kidney transplantation: a randomized controlled trial.

Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation after circulatory death (DCD) donors have been used to increase transplant rates, but these organs are susceptible to cold ischemic injury in the storage period before transplantation, the clinical consequence of which is high rates of delayed graft function (DGF). Normothermic machine perfusion (NMP) is an emerging technique that circulates a warmed, oxygenated red-cell-based perfusate through the kidney to maintain near-physiological conditions.

How to Best Protect Kidneys for Transplantation-Mechanistic Target.

The increasing number of patients on the kidney transplant waiting list underlines the need to expand the donor pool and improve kidney graft utilization. By protecting kidney grafts adequately from the initial ischemic and subsequent reperfusion injury occurring during transplantation, both the number and quality of kidney grafts could be improved. The last few years have seen the emergence of many new technologies to abrogate ischemia-reperfusion (I/R) injury, including dynamic organ preservation through machine perfusion and organ reconditioning therapies.

Honoring the gift: The transformative potential of transplant-declined human organs.

For decades, transplantation has been a life-saving treatment for those fortunate enough to gain access. Nevertheless, many patients die waiting for an organ and countless more never make it onto the waitlist because of a shortage of donor organs. Concurrently, thousands of donated organs are declined for transplant each year because of concerns about poor outcomes post-transplant.

Enzymatic blood group conversion of human kidneys during ex vivo normothermic machine perfusion.

A major restriction to transplantation is the requirement for ABO blood group compatibility between donor and recipient. In this study, an α-galactosidase enzyme from was used successfully to remove type B blood group antigens enzymatically from human kidneys using normothermic machine perfusion. This provides the first step for a strategy to overcome the ABO barrier in kidney transplantation.

The Effects of Free Heme on Functional and Molecular Changes During Normothermic Machine Perfusion of Human Kidneys.

Normothermic machine perfusion (NMP) is a technique of kidney preservation designed to restore cellular metabolism after cold ischemia. Kidneys are perfused with an oxygenated banked red blood cell (RBC) based solution for 1h at 36°C. During NMP, RBCs can become damaged, releasing free heme into the perfusate.

A digital pathology tool for quantification of color features in histologic specimens.

In preclinical research, histological analysis of tissue samples is often limited to qualitative or semiquantitative scoring assessments. The reliability of this analysis can be impaired by the subjectivity of these approaches, even when read by experienced pathologists. Furthermore, the laborious nature of manual image assessments often leads to the analysis being restricted to a relatively small number of images that may not accurately represent the whole sample.

Extracellular vesicles in kidney transplantation: a state-of-the-art review.

Kidney transplantation is the optimal treatment for patients with kidney failure; however, early detection and timely treatment of graft injury remain a challenge. Precise and noninvasive techniques of graft assessment and innovative therapeutics are required to improve kidney transplantation outcomes. Extracellular vesicles (EVs) are lipid bilayer-delimited particles with unique biosignatures and immunomodulatory potential, functioning as intermediaries of cell signalling.

A systematic review of living kidney donor enhanced recovery after surgery.

Enhanced recovery after surgery (ERAS) reduces complications and shortens hospital stay without increasing readmission or mortality. However, its role in living donor nephrectomy (LDN) has not yet been defined. Medline, Embase, CINAHL, PsycINFO, and Cochrane Central were searched prior to 08/01/21 for all randomized controlled and cohort studies comparing ERAS to standard of care in LDN.

Advances in Kidney Preservation Techniques and Their Application in Clinical Practice.

The use of cold preservation solutions to rapidly flush and cool the kidney followed by static cold storage in ice has been the standard kidney preservation technique for the last 50 y. Nonetheless, changing donor demographics that include organs from extended criteria donors and donation after circulatory death donors have led to the adoption of more diverse techniques of preservation. Comparison of hypothermic machine perfusion and static cold storage techniques for deceased donor kidneys has long been debated and is still contested by some.

Cytokine absorption during human kidney perfusion reduces delayed graft function-associated inflammatory gene signature.

Transplantation is the optimal treatment for most patients with end-stage kidney disease but organ shortage is a major challenge. Normothermic machine perfusion (NMP) has been used to recondition marginal organs; however, mechanisms by which NMP might benefit organs are not well understood. Using pairs of human kidneys obtained from the same donor, we compared the effect of NMP with that of cold storage on the global kidney transcriptome.

Treatment of transplant kidneys during machine perfusion.

The increasing use of donation after circulatory death (DCD) and extended criteria donor (ECD) organs has raised awareness of the need to improve the quality of kidneys for transplantation. Treating kidneys during the preservation interval could improve early and long-term graft function and survival. Dynamic modes of preservation including hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) may provide the functional platforms to treat these kidneys.

Pre-emptive immunosuppression using tacrolimus monotherapy does not reduce the rate of early acute rejection in renal transplantation from live donors: a comparative cohort study.

The planned nature of live donor kidney transplantation allows for immunosuppression to be initiated in the pretransplant period. The aim of this study was to determine the effect of pre-emptive immunosuppression on acute rejection rates after live donor kidney transplantation. In two consecutive cohorts of live donor kidneys transplants, 99 patients received pre-emptive immunosuppression with tacrolimus monotherapy for 2 weeks prior to transplantation (PET group - first era) and 100 patients received tacrolimus-based immunosuppression commencing on the day of transplantation (control group - second era).

Anastomosis of dual renal transplant veins.

As there is usually considerable overlap in the renal venous drainage, it is often possible to ligate supernumerary transplant renal veins in order to simplify the implantation procedure. Nonetheless, decisions about whether to implant multiple veins can be difficult and are usually made subjectively. Here, we describe the use of intraoperative Doppler ultrasound as an adjunct to decision-making when there are two renal veins and a novel technique for the sequential anastomosis of dual veins.

Flavin Mononucleotide as a Biomarker of Organ Quality-A Pilot Study.

Background: Flavin mononucleotide (FMN), released from damaged mitochondrial complex I during hypothermic liver perfusion, has been shown to be predictive of 90-day graft loss. Normothermic machine perfusion (NMP) and normothermic regional perfusion (NRP) are used for organ reconditioning and quality assessment before transplantation. This pilot study aimed to investigate the changes of FMN levels during normothermic reperfusion of kidneys, livers, and lungs and examine whether FMN could serve as a biomarker to predict posttransplant allograft quality.

Normothermic kidney perfusion: An overview of protocols and strategies.

Normothermic machine perfusion (NMP) technologies are emerging as an important adjunct in organ preservation and transplantation. NMP can enable the reduction or avoidance of cold ischemia and allows for pretransplant measurement of function and metabolic status to assess the suitability of the organ for transplantation. The key requirement of NMP is to provide an environment that is protective to the organ, ensures optimal oxygen delivery and supports metabolic function.