A Retrospective Propensity Score Matched Analysis Reveals Superiority of Hypothermic Machine Perfusion over Static Cold Storage in Deceased Donor Kidney Transplantation

Gasteiger, Silvia; Berchtold, Valeria; Bösmüller, Claudia; Dostal, Lucie; Ulmer, Hanno; Bogensperger, Christina; Resch, Thomas; Rudnicki, Michael; Neuwirt, Hannes; Oberhuber, Rupert; Cardini, Benno; Scheidl, Stefan; Mayer, Gert; Öfner, Dietmar; Weißenbacher, Annemarie; Schneeberger, Stefan

doi:10.3390/jcm9072311

Cited by 9 publications

(13 citation statements)

References 34 publications

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“…( 1,2 ) Unlike CS, preservation at physiological temperature maintains metabolic processes which can prevent the accumulation of toxic metabolites, ( 3 ) allows assessment of graft condition prior to transplantation, and makes possible the delivery of therapeutic medications to the donor liver prior to transplantation. Previous investigations have shown that machine perfusion improves clinical outcomes for marginal organs, ( 4‐6 ) and a large prospective trial has already demonstrated the efficacy of NEVLP clinically. ( 7 )…”

mentioning

confidence: 99%

Interleukin‐10 and Transforming Growth Factor‐β Cytokines Decrease Immune Activation During Normothermic Ex Vivo Machine Perfusion of the Rat Liver

Carlson¹,

Pavan-Guimaraes²,

Verhagen³

et al. 2021

Liver Transpl.

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Normothermic ex vivo liver perfusion (NEVLP) is a novel system for organ preservation that may improve over static cold storage clinically and offers the chance for graft modification prior to transplantation. Although recent studies have shown the presence of inflammatory molecules during perfusion, none have yet shown the effects of NEVLP on liver-resident immune cell activation. We investigated the effects of NEVLP on liver-resident immune cell activation and assessed the ability of anti-inflammatory cytokines interleukin 10 (IL10) and transforming growth factor β (TGFβ) to improve organ function and reduce immune activation during perfusion. Rat livers were perfused for 4 hours at 37°C with or without the addition of 20 ng/mL of each IL10 and TGFβ (n = 7). Naïve and cold storage (4 hours at 4°C) livers served as controls (n = 4). Following preservation, gene expression profiles were assessed through single-cell RNA sequencing; dendritic cell and macrophage activation was measured by flow cytometry; and cytokine production was assessed by enzyme-linked immunosorbent assay. NEVLP induced a global inflammatory gene expression signature, most notably in liver-resident macrophages and dendritic cells, which was accompanied by an increase in cell-surface levels of major histocompatibility complex (MHC) II, CD40, and CD86. Immune activation was partially ameliorated by IL10 and TGFβ treatment, but no changes were observed in inflammatory cytokine production. Overall levels of liver damage and cellular apoptosis from perfusion were low, and liver function was improved with IL10 and TGFβ treatment. This is the first study to demonstrate that liver-resident immune cells gain an activated phenotype during NEVLP on both the gene and protein level and that this activation can be reduced through therapeutic intervention with IL10 and TGFβ.

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mentioning

confidence: 99%

Interleukin‐10 and Transforming Growth Factor‐β Cytokines Decrease Immune Activation During Normothermic Ex Vivo Machine Perfusion of the Rat Liver

Carlson¹,

Pavan-Guimaraes²,

Verhagen³

et al. 2021

Liver Transpl.

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“…Almost all kidneys underwent hypothermic machine perfusion in this study (> 90%). Pumping kidneys has been shown to decrease the incidence of DGF in DBD and DCD donor kidneys 38–40 . Additional studies and a Cochrane Review have even shown improved 1‐year and 3‐year graft survival rates for DCD donor kidneys preserved with machine perfusion compared to static cold storage 38,41 .…”

Section: Discussionmentioning

confidence: 99%

“…Pumping kidneys has been shown to decrease the incidence of DGF in DBD and DCD donor kidneys. [38][39][40] Additional studies and a Cochrane Review have even shown improved 1-year and 3-year graft survival rates for DCD donor kidneys preserved with machine perfusion compared to static cold storage. 38,41 New perfusion technologies such as Hypothermic Oxygenated Machine Perfusion (HOPE) and Normothermic Machine Preservation may provide additional benefits, but both of these technologies are in their infancy and require additional resources that may make widespread clinical use challenging.…”

Section: F I G U R E 1 Actuarial Patient Survival Rates Among the Fou...mentioning

confidence: 99%

Does prolonged cold ischemia affect outcomes in donation after cardiac death donor kidney transplants?

Harriman

Kazokov

Rogers

et al. 2022

Clinical Transplantation

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Background The purpose of this study was to analyze the combined effect of cold ischemia time (CIT) and donation after cardiac death (DCD, with requisite warm ischemia time, WIT) on kidney transplant (KT) outcomes. Methods Single center retrospective review of DCD KT recipients stratified by CIT. Results From 6/08 to 10/20, we performed 446 DCD KTs (115 CIT ≤20, 205 CIT 20–30, 88 CIT 30–40, 38 CIT ≥40 h). Mean WITs (26/25/27/23 min) and KDPI values (59%/55%/55%/59%) were similar while mean CITs (16.4/23.6/33.4/42.5 h) and pump times (10.3/13.6/16.1/20.4 h) differed across groups (P < .05). With a mean 6‐year follow‐up, patient survival (84%/84%/74%/84%) was similar. Kidney graft survival (GS) (72%/72%/56%/58%) and death censored GS (DCGS) (82%/80%/63%/67%) rates decreased whereas rates of primary nonfunction (PNF, .9%/2.4%/9.1%/7.9%) and delayed graft function (DGF) (36%/48%/50%/69%) increased with longer CIT (≥30 h, P < .05). Meaningful years free of dialysis, which we refer to as Allograft Life Years, were achieved in all cohorts (4.5/4.3/3.9/4.3 years per patient transplanted). Conclusion DCD donor kidneys with prolonged CIT (≥30 h) are associated with increased rates of DGF and PNF, along with decreased GS and DCGS. Despite this, Allograft Life Years were gained even with longer CITs, demonstrating the utility of using these allografts.

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“…HMP operates with a cold preservation solution and continuously perfuses the organ at a controlled, low flow [ 19 ]. HMP has been associated with significantly lower rates of delayed graft function (DGF) and an increased 1-year graft survival compared to SCS [ 20 , 21 , 22 , 23 , 24 ].…”

Section: Bridging Time To Transplantation—from Static Cold Storage To Machine Perfusionmentioning

confidence: 99%

Ex Vivo Mesenchymal Stem Cell Therapy to Regenerate Machine Perfused Organs

Bogensperger

Hofmann

Messner

et al. 2021

IJMS

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Transplantation represents the treatment of choice for many end-stage diseases but is limited by the shortage of healthy donor organs. Ex situ normothermic machine perfusion (NMP) has the potential to extend the donor pool by facilitating the use of marginal quality organs such as those from donors after cardiac death (DCD) and extended criteria donors (ECD). NMP provides a platform for organ quality assessment but also offers the opportunity to treat and eventually regenerate organs during the perfusion process prior to transplantation. Due to their anti-inflammatory, immunomodulatory and regenerative capacity, mesenchymal stem cells (MSCs) are considered as an interesting tool in this model system. Only a limited number of studies have reported on the use of MSCs during ex situ machine perfusion so far with a focus on feasibility and safety aspects. At this point, no clinical benefits have been conclusively demonstrated, and studies with controlled transplantation set-ups are urgently warranted to elucidate favorable effects of MSCs in order to improve organs during ex situ machine perfusion.

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A Retrospective Propensity Score Matched Analysis Reveals Superiority of Hypothermic Machine Perfusion over Static Cold Storage in Deceased Donor Kidney Transplantation

Cited by 9 publications

References 34 publications

Interleukin‐10 and Transforming Growth Factor‐β Cytokines Decrease Immune Activation During Normothermic Ex Vivo Machine Perfusion of the Rat Liver

Interleukin‐10 and Transforming Growth Factor‐β Cytokines Decrease Immune Activation During Normothermic Ex Vivo Machine Perfusion of the Rat Liver

Does prolonged cold ischemia affect outcomes in donation after cardiac death donor kidney transplants?

Ex Vivo Mesenchymal Stem Cell Therapy to Regenerate Machine Perfused Organs

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