Reconditioning by end‐ischemic hypothermic in‐house machine perfusion: A promising strategy to improve outcome in expanded criteria donors kidney transplantation

Gallinat, Anja; Amrillaeva, Vera; Hoyer, Dieter P.; Kocabayoglu, Peri; Benkő, Tamás; Treckmann, Jürgen; Meel, Marieke van; Samuel, Undine; Minor, Thomas; Paul, Andreas

doi:10.1111/ctr.12904

Cited by 33 publications

(42 citation statements)

References 27 publications

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“…Whereas the treatment of brain dead donors has been addressed in only a small number of clinical trials (29–31), conditioning of the organ by machine perfusion is currently considered in a clearly larger number of clinical trials (4, 6, 32–34). These studies mainly address the impact of hypothermic vs. cold storage machine perfusion, whereas alternative approaches for organ conditioning are tested solely in pre-clinical models (35–37) or have been proven insufficient (38).…”

Section: Discussionmentioning

confidence: 99%

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period—a Prospective, Randomized Placebo-Controlled Trial

et al. 2018

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Introduction: Although prone to a higher degree of ischemia reperfusion injury (IRI), the use of extended criteria donor (ECD) organs has become reality in transplantation. We therefore postulated that peri-operative perfusion of renal transplants with anti-human T-lymphocyte globulin (ATLG) ameliorates IRI and results in improved graft function.Methods: We performed a randomized, single-blinded, placebo-controlled trial involving 50 kidneys (KTx). Prior to implantation organs were perfused and incubated with ATLG (AP) (n = 24 kidney). Control organs (CP) were perfused with saline only (n = 26 kidney). Primary endpoint was defined as graft function reflected by serum creatinine at day 7 post transplantation (post-tx).Results: AP-KTx recipients illustrated significantly better graft function at day 7 post-tx as reflected by lower creatinine levels, whereas no treatment effect was observed after 12 months surveillance. During the early hospitalization phase, 16 of the 26 CP-KTx patients required dialysis during the first 7 days post-tx, whereas only 10 of the 24 AP-KTx patients underwent dialysis. No treatment-specific differences were detected for various lymphocytes subsets in the peripheral blood of patients. Additionally, mRNA analysis of 0-h biopsies post incubation with ATLG revealed no changes of intragraft inflammatory expression patterns between AP and CP organs.Conclusion: We here present the first clinical study on peri-operative organ perfusion with ATLG illustrating improved graft function in the early period post kidney transplantation.Clinical Trial Registration: www.ClinicalTrials.gov, NCT03377283

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Section: Discussionmentioning

confidence: 99%

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period—a Prospective, Randomized Placebo-Controlled Trial

et al. 2018

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“…The authors believe the pulsatile stimulation of the renovasculature is an important reason for these results. It might preserve the vascular endothelium and its phenotype, preventing transcription of inflammatory and vasoconstrictors factors …”

Section: Discussionmentioning

confidence: 99%

“…The New York City OPO uses a hybrid strategy for kidneys allocated from a distant procured donor hospital (imported kidneys); these kidneys arrive after a mean CIT of 32 hours in preservation solution and ice and are connected to the MP when they arrive in New York City . However, the employment of machine perfusion following static cold storage vs the use of machine perfusion throughout the entire preservation period is still a matter of debate and recently has been investigated …”

Section: Introductionmentioning

confidence: 99%

Impact of machine perfusion after long static cold storage on delayed graft function incidence and duration and time to hospital discharge

Matos

Requião-Moura

Borrelli

et al. 2017

Clinical Transplantation

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Delayed graft function (DGF) is very high in our center (70%-80%), and we usually receive a kidney for transplant after more than 22 hours of static cold ischemia time (CIT). Also, there is an inadequate care of the donors, contributing to a high rate of DGF. We decided to test whether machine perfusion (MP) after a CIT improved the outcome of our transplant patients. We analyzed the incidence of DGF, its duration, and the length of hospital stay (LOS) in patients who received a kidney preserved with MP after a CIT (hybrid perfusion-HP). We included 54 deceased donors kidneys preserved with HP transplanted from Feb/13 to Jul/14, and compared them to 101 kidney transplants preserved by static cold storage (CS) from Nov/08 to May/12. The median pumping time was 11 hours. DGF incidence was 61.1% vs 79.2% (P = .02), median DGF duration was 5 vs 11 days (P < .001), and median LOS was 13 vs 18 days (P < .011), for the HP compared to CS group. The observed reduction of DGF with machine perfusion did not occur in donors over 50 years old. In the multivariate analysis, risk factors for DGF, adjusted for CIT, were donor age (OR, 1.04; P = .005) and the absence of use of MP (OR, 1.54; P = .051). In conclusion, the use of HP contributed to faster recovery of renal function and to a shorter length of hospital stay. K E Y W O R D Sdelayed graft function, kidney (allograft) function/dysfunction, organ perfusion and preservation

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“…18 In a rodent model reported by This strategy could be an interesting tool to decrease the DGF rate, especially in transplant programs dealing with a high incidence of DGF.…”

Section: Evolution Of Postoperative Serum Ldh and Astmentioning

confidence: 98%

“…11 Static cold storage (SCS) alone is the worldwide "gold standard" for organ preservation. 17 More recently, end-ischemic strategies have been shown to decrease the incidence of DGF by using HMP 18 or normothermic perfusion (NP) 19 after a period of SCS compared with SCS alone. 12,13 Continuous hypothermic machine perfusion (HMP) started immediately after procurement until implantation demonstrated better transplant outcomes compared with SCS alone [14][15][16] and reduced the risk of DGF regardless of donor type and cold ischemia time.…”

mentioning

confidence: 99%

The effect on early renal function of various dynamic preservation strategies in a preclinical pig ischemia–reperfusion autotransplant model

Darius¹,

Gianello

Vergauwen

et al. 2019

American Journal of Transplantation

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The aims of this study were to determine the most optimal timing to start machine perfusion during kidney preservation to improve early graft function and to evaluate the impact of temperature and oxygen supply during machine perfusion in a porcine ischemia-reperfusion autotransplant model. The left kidney of an approximately 40-kg female Belgian Landrace pig was exposed to 30 minutes of warm ischemia via vascular clamping and randomized to 1 of 6 study groups: (1) 22-hour static cold storage (SCS) (n = 6), (2) 22-hour hypothermic machine perfusion (HMP) (n = 6), (3) 22-hour oxygenated HMP (n = 7), (4) 20-hour HMP plus 2-hour normothermic perfusion (NP) (n = 6), (5) 20-hour SCS plus 2-hour oxygenated HMP (n = 7), and (6) 20-hour SCS plus 2-hour NP (n = 6). Graft recovery measured by serum creatinine level was significantly faster for continuous HMP preservation strategies compared with SCS alone and for all end-ischemic strategies. The active oxygenated 22-hour HMP group demonstrated a significantly faster recovery from early graft function compared with the 22-hour nonactive oxygenated HMP group. Active oxygenation was also found to be an important modulator of a faster increase in renal flow during HMP preservation. Continuous oxygenated HMP applied from the time of kidney procurement until transplant might be the best preservation strategy to improve early graft function.

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Reconditioning by end‐ischemic hypothermic in‐house machine perfusion: A promising strategy to improve outcome in expanded criteria donors kidney transplantation

Cited by 33 publications

References 27 publications

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period—a Prospective, Randomized Placebo-Controlled Trial

Graft Pre-conditioning by Peri-Operative Perfusion of Kidney Allografts With Rabbit Anti-human T-lymphocyte Globulin Results in Improved Kidney Graft Function in the Early Post-transplantation Period—a Prospective, Randomized Placebo-Controlled Trial

Impact of machine perfusion after long static cold storage on delayed graft function incidence and duration and time to hospital discharge

The effect on early renal function of various dynamic preservation strategies in a preclinical pig ischemia–reperfusion autotransplant model

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