Alkaline phosphatase supplementation during hypothermic and normothermic machine perfusion improves metabolic dysfunction in a porcine model of donor kidney preservation

Alkaline phosphatase supplementation during hypothermic and normothermic machine perfusion improves metabolic dysfunction in a porcine model of donor kidney preservation | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 11 December 2025 V1 Latest version Share on Alkaline phosphatase supplementation during hypothermic and normothermic machine perfusion improves metabolic dysfunction in a porcine model of donor kidney preservation Authors : Juan Miguel Tellez Garcia 0009-0004-6771-1664 , Thei Steenvoorden 0000-0001-6953-3647 , Joost van der Heijden , Frederike Bemelman , Janneke Rood , Sandrine Florquin , Alessandra Tammaro , Henri Leuvenink , and Liffert Vogt [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.176545941.12580375/v1 177 views 164 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background Kidney preservation techniques such as hypothermic machine perfusion (HMP) improve graft outcome in deceased-donor kidney transplantation through paused graft metabolism and ameliorated ischemia reperfusion injury (IRI) but do not nullify injury. Alkaline phosphatase (ALP) has been postulated to reduce IRI-induced kidney injury through the conversion of extracellular adenosine triphosphate into adenosine. The aim of the study was to evaluate if ALP offers protection during deceased-donor kidney storage. Methods Sixteen abattoir porcine kidneys (eight ALP and eight with placebo) were procured following sacrifice and exposed to 30 minutes of warm ischemia followed by 24h of HMP or static cold storage (SCS). Reperfusion was partly simulated by 240 minutes of normothermic machine perfusion (NMP). Throughout NMP, we obtained functional, biochemical parameters and histology. Results Significantly lower urine production accompanied by lower perfusate pCO2 and higher pH were observed in the ALP-group throughout NMP. At the end of NMP, intracellular ATP reserves and oxygen consumption were significantly higher in the ALP-treated group. Metabolomics analysis with PCA demonstrated significant differences between the ALP and placebo group regarding glycolysis and mitochondrial metabolites together with a significantly attenuated rise in levels of perfusate lactate dehydrogenase (LDH). Conclusion ALP supplementation during HMP was associated with lower urine production and energetic stress, with a shift towards less metabolic dysfunction and graft injury by the end of NMP. Our findings suggest an improvement of the early metabolic incompetency which characterizes delayed graft function (DGF) in humans. Further research should elucidate whether these findings indeed result in improvements of graft functionality following transplantation. Supplementary Material File (pig kidney machine fjp.docx) Download 1.77 MB Information & Authors Information Version history V1 Version 1 11 December 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Authors Affiliations Juan Miguel Tellez Garcia 0009-0004-6771-1664 Amsterdam UMC Locatie AMC Afdeling Inwendige Geneeskunde View all articles by this author Thei Steenvoorden 0000-0001-6953-3647 Amsterdam UMC Locatie AMC Afdeling Inwendige Geneeskunde View all articles by this author Joost van der Heijden Spaarne Gasthuis Haarlem-noord View all articles by this author Frederike Bemelman Amsterdam UMC Locatie AMC Afdeling Inwendige Geneeskunde View all articles by this author Janneke Rood Amsterdam UMC Locatie AMC Afdeling Inwendige Geneeskunde View all articles by this author Sandrine Florquin Amsterdam UMC Locatie AMC Afdeling Pathologie View all articles by this author Alessandra Tammaro Amsterdam Cardiovascular Sciences View all articles by this author Henri Leuvenink Universitair Medisch Centrum Groningen View all articles by this author Liffert Vogt [email protected] Amsterdam UMC Locatie AMC Afdeling Inwendige Geneeskunde View all articles by this author Metrics & Citations Metrics Article Usage 177 views 164 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Juan Miguel Tellez Garcia, Thei Steenvoorden, Joost van der Heijden, et al. Alkaline phosphatase supplementation during hypothermic and normothermic machine perfusion improves metabolic dysfunction in a porcine model of donor kidney preservation. Authorea . 11 December 2025. DOI: https://doi.org/10.22541/au.176545941.12580375/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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