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Ex-vivo Kidney Machine Perfusion: Therapeutic Potential.

ABSTRACT: Kidney transplantation remains the gold standard treatment for patients suffering from end-stage kidney disease. To meet the constantly growing organ demands grafts donated after circulatory death (DCD) or retrieved from extended criteria donors (ECD) are increasingly utilized. Not surprisingly, usage of those organs is challenging due to their susceptibility to ischemia-reperfusion injury, high immunogenicity, and demanding immune regulation after implantation. Lately, a lot of effort has been put into improvement of kidney preservation strategies. After demonstrating a definite advantage over static cold storage in reduction of delayed graft function rates in randomized-controlled clinical trials, hypothermic machine perfusion has already found its place in clinical practice of kidney transplantation. Nevertheless, an active investigation of perfusion variables, such as temperature (normothermic or subnormothermic), oxygen supply and perfusate composition, is already bringing evidence that ex-vivo machine perfusion has a potential not only to maintain kidney viability, but also serve as a platform for organ conditioning, targeted treatment and even improve its quality. Many different therapies, including pharmacological agents, gene therapy, mesenchymal stromal cells, or nanoparticles (NPs), have been successfully delivered directly to the kidney during ex-vivo machine perfusion in experimental models, making a big step toward achievement of two main goals in transplant surgery: minimization of graft ischemia-reperfusion injury and reduction of immunogenicity (or even reaching tolerance). In this comprehensive review current state of evidence regarding ex-vivo kidney machine perfusion and its capacity in kidney graft treatment is presented. Moreover, challenges in application of these novel techniques in clinical practice are discussed.

SUBMITTER: Zulpaite R

PROVIDER: S-EPMC8741203 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background. Ex vivo normothermic machine perfusion (NMP) has improved organ preservation and viability assessment among heart, liver, and lung transplantation. However, literature regarding the application of NMP in human clinical kidney transplantation remains limited. Numerous kidneys, especially from donors with stage 3 acute kidney injury (AKI), are not utilized concerning the high rate of delayed graft function (DGF) and primary nonfunction. The present study investigated the impact of NMP (135–150 min) on short-term outcomes after kidney transplantation from deceased donors with AKI. Methods. Graft outcomes of NMP kidneys were compared with contralateral kidneys stored in static cold storage (SCS) from the same donor with AKI during December 2019–June 2021. The study’s primary aim is to assess the safety and feasibility of NMP in deceased donors with AKI. The primary outcome was DGF. Secondary outcomes were duration of DGF, biopsy-proven rejection, postoperative intrarenal resistive index, postoperative infections, hospital stay duration, primary nonfunction, and kidney function estimated glomerular filtrate rate at discharge, 3 mo, and 1 y. Results. Five pairs of AKI kidneys (NMP versus SCS) were included in the final analysis. The results show no statistically significant differences in clinical outcomes between NMP versus SCS kidneys; however, NMP kidneys demonstrated slightly improved estimated glomerular filtrate rate at 3 mo (59.8 ± 5.93 [59] versus 75.20 ± 14.94 [74]) mL/min/1.73 m2 (P < 0.065) and at the last follow-up (12–29 mo) (72.80 ± 10.71 [75]) versus (94 ± 22.67 [82]) mL/min/1.73 m2 (P < 0.059) as compared with SCS kidneys. A higher proportion of NMP kidneys had normal intrarenal resistive index (0.5–0.7) and mild acute tubular injury on protocol biopsy, suggesting NMP is safe and feasible in deceased donors with acute kidney injury. Conclusions. NMPs of AKI donor kidneys are safe and feasible. A larger cohort is required to explore the reconditioning effect of NMP on AKI kidneys.

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Ex-vivo Kidney Machine Perfusion: Therapeutic Potential.

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