Tim L Hamelink, Baran Ogurlu, Chris L Jaynes, Veerle A Lantinga, Henri G D Leuvenink, Anna K Keller, Cyril Moers
{"title":"Perfusate Biomarker Comparison During Renal Hypothermic and Normothermic Machine Perfusion: Do These Techniques Provide Similar Insights?","authors":"Tim L Hamelink, Baran Ogurlu, Chris L Jaynes, Veerle A Lantinga, Henri G D Leuvenink, Anna K Keller, Cyril Moers","doi":"10.1097/TP.0000000000005440","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) are increasingly used in renal transplantation. Both techniques enable pretransplant organ viability assessment through biomarker measurements in the perfusion solution. This study examines similarities and differences in biomarker release during HMP and NMP, focusing on well-established biomarkers alongside functional markers in porcine and discarded human donor kidneys.</p><p><strong>Methods: </strong>Discarded human donor kidneys (n = 25) underwent 4 h of oxygenated hypothermic machine perfusion (HMPO 2 ) and subsequently 4 h of NMP. Porcine kidneys were exposed to either minimal warm ischemia or 75 min of warm ischemia (n = 30 per group). Hereafter, kidneys were placed on HMPO 2 for 6 h followed by 6 h of NMP. Flow dynamics were recorded, and the biomarkers aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), N -acetyl-β-glucosaminidase, tissue inhibitor of metalloproteinases-2 (TIMP-2), and heart-type fatty acid-binding protein were measured longitudinally in the perfusates.</p><p><strong>Results: </strong>For human kidneys, we found moderate to strong correlations between ASAT, LDH, TIMP-2, and heart-type fatty acid-binding protein content measured during HMPO 2 and the same biomarkers during NMP. In porcine kidneys, clear distinctions between ischemically damaged and healthy kidneys were observed in flow dynamics and content of ASAT, LDH, and TIMP-2 during both HMPO 2 and NMP.</p><p><strong>Conclusions: </strong>Our findings suggest that biomarker release during HMPO 2 and NMP have similarities, indicating that some biomarkers might already be assessed during HMPO 2 . However, the predictive value of biomarkers in both techniques remains elusive. Additionally, NMP could provide important benefits over HMPO 2 , including functional assessment and reconditioning.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"e554-e566"},"PeriodicalIF":5.0000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453108/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Transplantation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/TP.0000000000005440","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/9 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) are increasingly used in renal transplantation. Both techniques enable pretransplant organ viability assessment through biomarker measurements in the perfusion solution. This study examines similarities and differences in biomarker release during HMP and NMP, focusing on well-established biomarkers alongside functional markers in porcine and discarded human donor kidneys.
Methods: Discarded human donor kidneys (n = 25) underwent 4 h of oxygenated hypothermic machine perfusion (HMPO 2 ) and subsequently 4 h of NMP. Porcine kidneys were exposed to either minimal warm ischemia or 75 min of warm ischemia (n = 30 per group). Hereafter, kidneys were placed on HMPO 2 for 6 h followed by 6 h of NMP. Flow dynamics were recorded, and the biomarkers aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH), N -acetyl-β-glucosaminidase, tissue inhibitor of metalloproteinases-2 (TIMP-2), and heart-type fatty acid-binding protein were measured longitudinally in the perfusates.
Results: For human kidneys, we found moderate to strong correlations between ASAT, LDH, TIMP-2, and heart-type fatty acid-binding protein content measured during HMPO 2 and the same biomarkers during NMP. In porcine kidneys, clear distinctions between ischemically damaged and healthy kidneys were observed in flow dynamics and content of ASAT, LDH, and TIMP-2 during both HMPO 2 and NMP.
Conclusions: Our findings suggest that biomarker release during HMPO 2 and NMP have similarities, indicating that some biomarkers might already be assessed during HMPO 2 . However, the predictive value of biomarkers in both techniques remains elusive. Additionally, NMP could provide important benefits over HMPO 2 , including functional assessment and reconditioning.
期刊介绍:
The official journal of The Transplantation Society, and the International Liver Transplantation Society, Transplantation is published monthly and is the most cited and influential journal in the field, with more than 25,000 citations per year.
Transplantation has been the trusted source for extensive and timely coverage of the most important advances in transplantation for over 50 years. The Editors and Editorial Board are an international group of research and clinical leaders that includes many pioneers of the field, representing a diverse range of areas of expertise. This capable editorial team provides thoughtful and thorough peer review, and delivers rapid, careful and insightful editorial evaluation of all manuscripts submitted to the journal.
Transplantation is committed to rapid review and publication. The journal remains competitive with a time to first decision of fewer than 21 days. Transplantation was the first in the field to offer CME credit to its peer reviewers for reviews completed.
The journal publishes original research articles in original clinical science and original basic science. Short reports bring attention to research at the forefront of the field. Other areas covered include cell therapy and islet transplantation, immunobiology and genomics, and xenotransplantation.