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. Therapies in the field of regenerative medicine including cellular therapies and genetic modification and the application of biological agents targeting ischaemia reperfusion injury (IRI) and acute rejection are a growing area of research. This review reports on the application of cellular and gene manipulating therapies, nanoparticles, anti-inflammatory agents, anti-thrombolytic agents and monoclonal antibodies administered during HMP and NMP in experimental models. The review also reports on the clinical effectiveness of several biological agents administered during HMP. All of the experimental studies provide proof of principle that therapies can be successfully delivered during HMP and NMP. However, few have examined the effects after transplantation. Evidence for clinical application during HMP is sparse and only one study has demonstrated a beneficial effect on graft function. More investigation is needed to develop perfusion strategies and investigate the different experimental approaches.

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). The main outcome measure was the incidence of biopsy-proven acute rejection (BPAR) in the first 3 months post-transplantation. Tacrolimus levels were significantly higher in the PET group at day 4 post-transplant (PET 9.08 ± 4.57 vs. control 5.92 ± 3.64 ng/ml; P < 0.0001), but there were no significant differences in tacrolimus levels at day 7 (PET 8.22 ± 3.58 vs. control 7.63 ± 3.56 ng/ml; P = 0.2452). BPAR was numerically higher in the PET group, but this difference did not reach statistical significance (PET 13/99 vs. control 6/100; P = 0.097). There were no differences in allograft function measured by serum creatinine at 1 year (PET 130 ± 36 vs. control 142 ± 69 µmol/l; P = 0.6829). Graft survival at 1 year was equivalent in both groups (PET 96.9 vs. control 97.0%; P = 0.9915). This study suggests that there is little role for the use of pre-emptive tacrolimus monotherapy in ABO blood group and HLA-compatible live donor kidney transplantation in patients on triple maintenance immunosuppression.

Novel Assessment (BlueDop) Device for Detection of Lower Limb Arterial Disease: A Prospective Comparative Study.

According to National Institute of Clinical Excellence guidelines, the ankle-brachial pressure index coupled with a full clinical evaluation has been the mainstay of detecting peripheral arterial disease on its suspicion. However, this technique is not free of its own limitations in calcified arteries, ulcerative and diabetic patients. We introduce a new, novel, and effective assessment device (BlueDop) with a minimal learning curve that could overcome such barriers and serve as a valid replacement in perihospital settings.

Portal venous repopulation of decellularised rat liver scaffolds with syngeneic bone marrow stem cells.

Liver transplantation is the only life-saving treatment for end-stage liver failure but is limited by the organ shortage and consequences of immunosuppression. Repopulation of decellularised scaffolds with recipient cells provides a theoretical solution, allowing reliable and timely organ sourcing without the need for immunosuppression. Recellularisation of the vasculature of decellularised liver scaffolds was investigated as an essential prerequisite to the survival of other parenchymal components. Liver decellularisation was carried out by portal vein perfusion using a detergent-based solution. Decellularised scaffolds were placed in a sterile perfusion apparatus consisting of a sealed organ chamber, functioning at 37°C in normal atmospheric conditions. The scaffold was perfused via portal vein with culture medium. A total of 107 primary cultured bone marrow stem cells, selected by plastic adherence, were infused into the scaffold, after which repopulated scaffolds were perfused for up to 30 days. The cultured stem cells were assessed for key marker expression using fluorescence-activated cell sorting (FACS), and recellularised scaffolds were analysed by light, electron and immunofluorescence microscopy. Stem cells were engrafted in portal, sinusoidal and hepatic vein compartments, with cell alignment reminiscent of endothelium. Cell surface marker expression altered following engraftment, from haematopoietic to endothelial phenotype, and engrafted cells expressed sinusoidal endothelial endocytic receptors (mannose, Fc and stabilin receptors). These results represent one step towards complete recellularisation of the liver vasculature and progress towards the objective of generating transplantable neo-organs.

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. The kidney was reperfused after anastomosis of the main renal vein with the second vein clamped. On-table Doppler ultrasound demonstrated reversed flow in diastole indicating that the second renal vein also needed to be anastomosed. By clamping the external iliac vein inferior to the first venous anastomosis it was possible to complete the lower polar renal vein anastomosis to the external iliac vein without interrupting the perfusion of the kidney.

The independent association of preoperative serum albumin on the functional maturation of radiocephalic arteriovenous fistulae.

PURPOSE: The aim of this study is to test the null hypothesis that preoperative albumin along with other preoperative confounders have no impact on the functional maturation of radiocephalic arteriovenous fistulae (RCAVF). METHODS: A retrospective cohort study of n = 195 individuals undergoing RCAVF formation from July 2013 to December 2015 was conducted. The null hypothesis was assessed through chi squared test. Independent association of each variable was evaluated through univariate and multivariate logistic regression model. Pearson's correlation test was also performed between scale variables to establish their causal link. RESULTS: Preoperative hypoalbuminaemic group of individuals demonstrated significant failure of maturation (49.3% vs. 27.2%, p = 0.002). At multivariate analysis, hypoalbuminemia remained an independent marker of fistula failure (OR 0.40, 95% CI 0.21-0.76, p = 0.004) and demonstrated a weak but a positive correlation at the endpoint of maturation (R = 0.223, p = 0.002). CONCLUSIONS: Preoperative hypoalbuminemia (<35 mg/dL) is independently associated with 40% reduction in the functional maturation of RCAVF. Stratification of this readily available biomarker prior to RCAVF formation may require consideration subjected to further research.