{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:32:03Z","timestamp":1786480323016,"version":"build-2736575974"},"reference-count":19,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2026,3]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n Physiological normothermic machine perfusion kept kidneys viable for 12 hours with better hemodynamics, urine output, and metabolic stability than clinical normothermic machine perfusion.<\/jats:p>\n <\/jats:list-item>\n \n Physiological normothermic machine perfusion reduced injury (lower urinary neutrophil gelatinase-associated lipocalin), improved histology\/appearance, and increased clinical suitability versus clinical normothermic machine perfusion.<\/jats:p>\n <\/jats:list-item>\n \n Prolonged physiological preservation could electivize surgery, improve early function, and expand donor kidney utilization.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Hypothermic donor kidney preservation contributes to graft injury, leading to substantial discard rates and peritransplant nephron loss. Normothermic machine perfusion may offer superior preservation, but current clinical protocols are restrictive because of time-dependent injury. On these grounds, we performed a paired preclinical evaluation of a novel physiological NMP (pNMP) protocol versus the current clinical NMP (cNMP) protocol used in the United Kingdom over a 12-hour perfusion period.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Paired porcine kidneys underwent standard retrieval and cold storage before randomization to either cNMP or our pNMP. Both groups were perfused for 12 hours while monitoring hemodynamics, biochemistry, and urine output.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Kidneys preserved with pNMP exhibited superior perfusion, with improving hemodynamics and metabolic function within physiological ranges. Urine output was stable with a low concentration of the renal injury marker neutrophil gelatinase-associated lipocalin, indicating improved tissue viability. By contrast, cNMP kidneys exhibited evidence of hemodynamic compromise, with polyuria. Histological analyses of cNMP kidneys confirmed AKI. All pNMP kidneys were assessed as suitable for transplant on the basis of clinical assessment score, while several cNMP kidneys were considered marginal.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The pNMP protocol improved preservation of donor kidneys compared with the cNMP protocol. Successful prolonged organ preservation could transform clinical kidney transplantation by obviating night implantation and has further potential benefits for improving post-transplant outcomes and expanding the donor pool.<\/jats:p>\n <\/jats:sec>","DOI":"10.34067\/kid.0000001055","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T17:00:50Z","timestamp":1765299650000},"page":"515-526","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":1,"title":["Physiological Normothermic Machine Perfusion Enhances Kidney Preservation Versus the Established UK Normothermic Machine Perfusion Assessment Protocol"],"prefix":"10.34067","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9452-2843","authenticated-orcid":false,"given":"John P.","family":"Stone","sequence":"first","affiliation":[{"name":"Pebble Institute, Manchester, United Kingdom"},{"name":"Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3731-0083","authenticated-orcid":false,"given":"William","family":"Norton","sequence":"additional","affiliation":[{"name":"Department of Renal Transplantation, NHS Greater Glasgow and Clyde-Queen Elizabeth University Hospital, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0388-1148","authenticated-orcid":false,"given":"William R.","family":"Cowey","sequence":"additional","affiliation":[{"name":"Pebble Institute, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6883-9593","authenticated-orcid":false,"given":"Emily L.","family":"Milburn","sequence":"additional","affiliation":[{"name":"Pebble Institute, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6384-7658","authenticated-orcid":false,"given":"Georgina E.","family":"Chesworth","sequence":"additional","affiliation":[{"name":"Pebble Institute, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6477-6465","authenticated-orcid":false,"given":"Amy F.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Pebble Institute, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4970-553X","authenticated-orcid":false,"given":"Corban J.T.","family":"Bowers","sequence":"additional","affiliation":[{"name":"Pebble Institute, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9751-0661","authenticated-orcid":false,"given":"Emanuele","family":"Ricci","sequence":"additional","affiliation":[{"name":"Faculty of Health and Life Sciences, Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Entwistle","sequence":"additional","affiliation":[{"name":"Pebble Institute, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6545-7894","authenticated-orcid":false,"given":"Kavit","family":"Amin","sequence":"additional","affiliation":[{"name":"Pebble Institute, Manchester, United Kingdom"},{"name":"Blond McIndoe Laboratories, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, United Kingdom"},{"name":"Department of Plastic Surgery and Burns, Wythenshawe Hospital, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Clancy","sequence":"additional","affiliation":[{"name":"Department of Renal Transplantation, NHS Greater Glasgow and Clyde-Queen Elizabeth University Hospital, Glasgow, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Fildes","sequence":"additional","affiliation":[{"name":"Pebble Institute, Manchester, United Kingdom"},{"name":"Department of Plastic Surgery and Burns, Wythenshawe Hospital, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"issue":"2","key":"B4-20260330","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1038\/ki.2014.304","article-title":"Each additional hour of cold ischemia time significantly increases the risk of graft failure and mortality following renal transplantation","volume":"87","author":"Debout","year":"2015","journal-title":"Kidney Int."},{"issue":"5","key":"B5-20260330","doi-asserted-by":"crossref","first-page":"11232","DOI":"10.3389\/ti.2023.11232","article-title":"Kidney transplantation donors with acute kidney injury: are the concerns justified? A Systematic Review and Meta-Analysis","volume":"36","author":"Nita","year":"2023","journal-title":"Transpl Int."},{"issue":"2","key":"B6-20260330","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1681\/ASN.2020040464","article-title":"Assessment of the utility of kidney histology as a basis for discarding organs in the United States: a comparison of international transplant practices and outcomes","volume":"32","author":"Reese","year":"2021","journal-title":"J Am Soc Nephrol."},{"issue":"2","key":"B7-20260330","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3390\/transplantology5020006","article-title":"Wasted potential: decoding the trifecta of donor kidney shortage, underutilization, and rising discard rates","volume":"5","author":"McKenney","year":"2024","journal-title":"Transplantology."},{"issue":"6","key":"B8-20260330","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1038\/s41591-023-02376-7","article-title":"Normothermic machine perfusion versus static cold storage in donation after circulatory death kidney transplantation: a randomized controlled trial","volume":"29","author":"Hosgood","year":"2023","journal-title":"Nat Med."},{"issue":"12","key":"B9-20260330","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1097\/MAT.0000000000002236","article-title":"Developing an injury-free 15 hour preservation protocol of donor porcine kidneys using normothermic machine perfusion","volume":"70","author":"Stone","year":"2024","journal-title":"ASAIO J."},{"issue":"7","key":"B10-20260330","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1097\/TP.0b013e31822d4e04","article-title":"First in man renal transplantation after ex vivo normothermic perfusion","volume":"92","author":"Hosgood","year":"2011","journal-title":"Transplantation."},{"issue":"11","key":"B11-20260330","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1002\/bjs.9894","article-title":"Ex vivo normothermic perfusion for quality assessment of marginal donor kidney transplants","volume":"102","author":"Hosgood","year":"2015","journal-title":"Br J Surg."},{"issue":"1","key":"B12-20260330","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ebiom.2018.01.025","article-title":"Ischemia-reperfusion injury reduces long term renal graft survival: mechanism and beyond","volume":"28","author":"Zhao","year":"2018","journal-title":"EBioMedicine."},{"issue":"10","key":"B13-20260330","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.3390\/jpm12101557","article-title":"Delayed graft function in kidney transplant: risk factors, consequences and prevention strategies","volume":"12","author":"Ponticelli","year":"2022","journal-title":"J Pers Med."},{"issue":"56 (suppl 72)","key":"B14-20260330","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1046\/j.1523-1755.56.s72.5.x","article-title":"Acid-base balance and substitution fluid during continuous hemofiltration","author":"Heering","year":"1999","journal-title":"Kidney Int Suppl."},{"issue":"2","key":"B15-20260330","doi-asserted-by":"crossref","first-page":"R60","DOI":"10.1186\/cc2423","article-title":"Occult hypoperfusion is associated with increased mortality in hemodynamically stable, high-risk, surgical patients","volume":"8","author":"Meregalli","year":"2004","journal-title":"Crit Care."},{"issue":"4","key":"B16-20260330","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1051\/ject\/200840257","article-title":"Hemolysis in cardiac surgery patients undergoing cardiopulmonary bypass: a review in search of a treatment algorithm","volume":"40","author":"Vercaemst","year":"2008","journal-title":"J Extra Corpor Technol."},{"issue":"17","key":"B17-20260330","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1182\/blood.2022015596","article-title":"Hemolysis, free hemoglobin toxicity, and scavenger protein therapeutics","volume":"140","author":"Vallelian","year":"2022","journal-title":"Blood."},{"issue":"5","key":"B18-20260330","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1097\/SLA.0000000000002044","article-title":"Low versus standard urine output targets in patients undergoing major abdominal surgery: a randomized noninferiority trial","volume":"265","author":"Puckett","year":"2017","journal-title":"Ann Surg."},{"issue":"4","key":"B19-20260330","doi-asserted-by":"crossref","first-page":"253","DOI":"10.4285\/kjt.22.0053","article-title":"Retrograde reperfusion of renal grafts to reduce ischemic-reperfusion injury","volume":"36","author":"Rysmakhanov","year":"2022","journal-title":"Korean J Transplant."},{"issue":"27","key":"B20-20260330","doi-asserted-by":"crossref","first-page":"E2817","DOI":"10.1073\/pnas.1402352111","article-title":"mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress","volume":"111","author":"Grahammer","year":"2014","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"5","key":"B21-20260330","doi-asserted-by":"crossref","first-page":"1714","DOI":"10.1046\/j.1523-1755.2003.00928.x","article-title":"Differential gene expression following early renal ischemia\/reperfusion","volume":"63","author":"Supavekin","year":"2003","journal-title":"Kidney Int."},{"issue":"7","key":"B22-20260330","doi-asserted-by":"crossref","first-page":"e14676","DOI":"10.1111\/ctr.14676","article-title":"Abnormal time-zero histology is predictive of kidney transplant outcomes","volume":"36","author":"Raza","year":"2022","journal-title":"Clin Transplant."}],"container-title":["Kidney360"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0000001055","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:03:41Z","timestamp":1786478621000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.34067\/KID.0000001055"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,8]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.34067\/kid.0000001055","relation":{},"ISSN":["2641-7650"],"issn-type":[{"value":"2641-7650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,8]]},"assertion":[{"value":"2025-07-17","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-24","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}