Perfusate Composition and Duration of Ex-Vivo Normothermic Perfusion in Kidney Transplantation: A Systematic Review

Transplant International. 2022;35:10236
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Abstract

Ex-vivo normothermic perfusion (EVNP) is an emerging strategy in kidney preservation that enables resuscitation and viability assessment under pseudo-physiological conditions prior to transplantation. The optimal perfusate composition and duration, however, remain undefined. A systematic literature search (Embase; Medline; Scopus; and BIOSIS Previews) was conducted. We identified 1,811 unique articles dating from January 1956 to July 2021, from which 24 studies were deemed eligible for qualitative analysis. The perfusate commonly used in clinical practice consisted of leukocyte-depleted, packed red blood cells suspended in Ringer's lactate solution with Mannitol, dexamethasone, heparin, sodium bicarbonate and a specific nutrient solution supplemented with insulin, glucose, multivitamins and vasodilators. There is increasing support in preclinical studies for non-blood cell-based perfusates, including Steen solution, synthetic haem-based oxygen carriers and acellular perfusates with supraphysiological carbogen mixtures that support adequate oxygenation whilst also enabling gradual rewarming. Extended durations of perfusion (up to 24 h) were also feasible in animal models. Direct comparison between studies was not possible due to study heterogeneity. Current evidence demonstrates safety with the aforementioned widely used protocol, however, extracellular base solutions with adequate oxygenation, supplemented with nutrient and metabolic substrates, show promise by providing a suitable environment for prolonged preservation and resuscitation. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021231381, identifier PROSPERO 2021 CRD42021231381.

CET Conclusion

Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
This is a well-conducted systematic review in Ex-Vivo Normothermic Perfusion (EVNP) of kidneys. It was registered with the PROSPERO system (CRD42021231381). A wide search was undertaken in multiple databases and two independent authors screened references. 24 studies were included, spanning both animal and human kidney studies. A variety of perfusate compositions are assessed in the included studies and the outcomes are not standardised. In combination, these factors make the included studies very heterogenous and not suitable for any summative analysis. The perfusate most commonly used in clinical studies primarily consisted of Ringer’s lactate and O-negative packed red cells. Accepting that the included studies are heterogenous and include pre-clinical and animal studies, this is a well-written and thorough review of this subject.

Study details

Aims : This study aimed to summarise the evidence for optimal perfusate constituents and duration of ex-vivo normothermic perfusion (EVNP) in the context of renal transplantation.
Interventions : A literature search was conducted on Embase, Medline, Scopus and BIOSIS Previews. Studies were screened by two independent reviewers.
Participants : 24 studies were included in the review.
Outcomes : The main outcomes of interest were perfusate composition and perfusion duration.
Follow up : N/A

Metadata

Funding : No funding was received for this study
Publication type : Systematic Review
Review registration : PROSPERO - CRD42021231381
Organ : Kidney
Language : English
Author email : Robert.pearson5@nhs.scot