{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:14:44Z","timestamp":1790194484887,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T00:00:00Z","timestamp":1667174400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["03INT502AB"],"award-info":[{"award-number":["03INT502AB"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["IM 20\/4-1"],"award-info":[{"award-number":["IM 20\/4-1"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Federal Ministry of Education and Research","doi-asserted-by":"publisher","award":["GU 613\/1-1"],"award-info":[{"award-number":["GU 613\/1-1"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["03INT502AB"],"award-info":[{"award-number":["03INT502AB"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["IM 20\/4-1"],"award-info":[{"award-number":["IM 20\/4-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GU 613\/1-1"],"award-info":[{"award-number":["GU 613\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cell-free hemoglobin (CFH), a pro-oxidant and cytotoxic compound that is released in hemolysis, has been associated with nephrotoxicity. Lung transplantation (LuTx) is a clinical condition with a high incidence of acute kidney injury (AKI). In this study, we investigated the plasma levels of CFH and haptoglobin, a CFH-binding serum protein, in prospectively enrolled LuTx patients (n = 20) with and without AKI. LuTx patients with postoperative AKI had higher CFH plasma levels at the end of surgery compared with no-AKI patients, and CFH correlated with serum creatinine at 48 h. Moreover, CFH levels inversely correlated with haptoglobin levels, which were significantly reduced at the end of surgery in LuTx patients with AKI. Because multiple other factors can contribute to AKI development in the complex clinical setting of LuTx, we next investigated the role of exogenous CFH administration in a mouse model of mild bilateral renal ischemia reperfusion injury (IRI). Exogenous administration of CFH after reperfusion caused overt AKI with creatinine increase, tubular injury, and enhanced markers of renal inflammation compared with vehicle-treated animals. In conclusion, CFH is a possible factor contributing to postoperative AKI after LuTx and promotes AKI in an experimental model of mild transient renal ischemia. Targeting CFH might be a therapeutic option to prevent AKI after LuTx.<\/jats:p>","DOI":"10.3390\/ijms232113272","type":"journal-article","created":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T06:01:28Z","timestamp":1667282488000},"page":"13272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cell-Free Hemoglobin in Acute Kidney Injury after Lung Transplantation and Experimental Renal Ischemia\/Reperfusion"],"prefix":"10.3390","volume":"23","author":[{"given":"Robert","family":"Greite","sequence":"first","affiliation":[{"name":"Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Gohlke","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Schott","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirill","family":"Kreimann","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Doricic","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1121-6387","authenticated-orcid":false,"given":"Andreas","family":"Leffler","sequence":"additional","affiliation":[{"name":"Anaesthesiology, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Tudorache","sequence":"additional","affiliation":[{"name":"Cardiac Surgery, University of Dusseldorf, 40225 Dusseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawad","family":"Salman","sequence":"additional","affiliation":[{"name":"Cardiac Surgery, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2219-3766","authenticated-orcid":false,"given":"Ruslan","family":"Natanov","sequence":"additional","affiliation":[{"name":"Cardiac Surgery, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Ius","sequence":"additional","affiliation":[{"name":"Cardiac Surgery, Hannover Medical School, 30625 Hannover, Germany"},{"name":"German Center for Lung Research (DZL), 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Fegbeutel","sequence":"additional","affiliation":[{"name":"Cardiac Surgery, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Haverich","sequence":"additional","affiliation":[{"name":"Cardiac Surgery, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Lichtinghagen","sequence":"additional","affiliation":[{"name":"Clinical Chemistry, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongjun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9985-1515","authenticated-orcid":false,"given":"Song","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Haller","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Hannover Medical School, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijith","family":"Vijayan","sequence":"additional","affiliation":[{"name":"Pediatrics, Stanford University, Stanford, CA 94305, 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Cardiovasc. Thorac. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.transproceed.2017.01.031","article-title":"Incidence of Early Acute Kidney Injury in Lung Transplant Patients: A Single-Center Experience","volume":"49","author":"Balci","year":"2017","journal-title":"Transpl. Proc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2215\/CJN.04800512","article-title":"Recovery from AKI and short- and long-term outcomes after lung transplantation","volume":"8","author":"Wehbe","year":"2013","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1161\/CIRCULATIONAHA.108.786913","article-title":"Acute kidney injury after cardiac surgery: Focus on modifiable risk factors","volume":"119","author":"Karkouti","year":"2009","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1161\/CIRCULATIONAHA.108.800011","article-title":"Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery","volume":"119","author":"Hobson","year":"2009","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.transproceed.2020.01.018","article-title":"Acute Kidney Injury After Lung Transplantation: Perioperative Risk Factors and Outcome","volume":"52","author":"Atchade","year":"2020","journal-title":"Transpl. Proc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1097\/CM9.0000000000001636","article-title":"Acute kidney injury following adult lung transplantation","volume":"135","author":"Jing","year":"2021","journal-title":"Chin. Med. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"17399","DOI":"10.1038\/s41598-021-96889-1","article-title":"Risk factors and mortality of acute kidney injury within 1 month after lung transplantation","volume":"11","author":"Kim","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1089\/ars.2009.2974","article-title":"The redox activity of hemoglobins: From physiologic functions to pathologic mechanisms","volume":"13","author":"Reeder","year":"2010","journal-title":"Antioxid. Redox Signal."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1182\/blood-2012-11-451229","article-title":"Hemolysis and free hemoglobin revisited: Exploring hemoglobin and hemin scavengers as a novel class of therapeutic proteins","volume":"121","author":"Schaer","year":"2013","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/s41581-019-0181-0","article-title":"Mechanisms of haemolysis-induced kidney injury","volume":"15","author":"Nur","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1136\/jim-2021-002008","article-title":"Interleukin-10 attenuates renal injury after myocardial infarction in diabetes","volume":"70","author":"Fan","year":"2022","journal-title":"J. Investig. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1111\/j.1432-2277.2007.00538.x","article-title":"Hemoglobin induces cytotoxic damage of glycine-preserved renal tubules","volume":"20","author":"Moussavian","year":"2007","journal-title":"Transpl. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1172\/JCI59770","article-title":"Hemoglobin-driven pathophysiology is an in vivo consequence of the red blood cell storage lesion that can be attenuated in guinea pigs by haptoglobin therapy","volume":"122","author":"Baek","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.bcmd.2014.12.001","article-title":"Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease","volume":"54","author":"Chintagari","year":"2015","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"F922","DOI":"10.1152\/ajprenal.00375.2018","article-title":"Cell-free hemoglobin augments acute kidney injury during experimental sepsis","volume":"317","author":"Shaver","year":"2019","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"R125","DOI":"10.1186\/cc11425","article-title":"Free hemoglobin concentration in severe sepsis: Methods of measurement and prediction of outcome","volume":"16","author":"Adamzik","year":"2012","journal-title":"Crit. Care"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Omar, H.R., Mirsaeidi, M., Socias, S., Sprenker, C., Caldeira, C., Camporesi, E.M., and Mangar, D. (2015). Plasma Free Hemoglobin Is an Independent Predictor of Mortality among Patients on Extracorporeal Membrane Oxygenation Support. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124034"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s13054-022-03894-5","article-title":"The role of cell-free hemoglobin and haptoglobin in acute kidney injury in critically ill adults with ARDS and therapy with VV ECMO","volume":"26","author":"Graw","year":"2022","journal-title":"Crit. Care"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e98546","DOI":"10.1172\/jci.insight.98546","article-title":"Cell-free hemoglobin promotes primary graft dysfunction through oxidative lung endothelial injury","volume":"3","author":"Shaver","year":"2018","journal-title":"JCI Insight"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1111\/j.1600-6143.2005.00867.x","article-title":"Acute renal failure after lung transplantation: Incidence, predictors and impact on perioperative morbidity and mortality","volume":"5","author":"Rocha","year":"2005","journal-title":"Am. J. Transplant."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.healun.2011.04.013","article-title":"Severe acute kidney injury according to the RIFLE (risk, injury, failure, loss, end stage) criteria affects mortality in lung transplantation","volume":"30","author":"Arnaoutakis","year":"2011","journal-title":"J. Heart Lung Transplant."},{"key":"ref_23","first-page":"193","article-title":"Acute renal failure following lung transplantation: Risk factors, mortality, and long-term consequences","volume":"41","author":"Jacques","year":"2012","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.healun.2011.08.016","article-title":"Short-term and long-term outcomes of acute kidney injury after lung transplantation","volume":"31","author":"Wehbe","year":"2012","journal-title":"J. Heart Lung Transplant."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1093\/ndt\/gfu226","article-title":"Incidence and outcomes of acute kidney injury following orthotopic lung transplantation: A population-based cohort study","volume":"29","author":"Fidalgo","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1097\/01.ASN.0000130340.93930.DD","article-title":"Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: A prospective cohort study","volume":"15","author":"Lassnigg","year":"2004","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/j.transproceed.2022.02.014","article-title":"Incidence and Perioperative Risk Factors of Acute Kidney Injury among Lung Transplant Recipients","volume":"54","author":"Nadziakiewicz","year":"2022","journal-title":"Transplant. Proc."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s00228-017-2204-8","article-title":"High tacrolimus blood concentrations early after lung transplantation and the risk of kidney injury","volume":"73","author":"Sikma","year":"2017","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Doricic, J., Greite, R., Vijayan, V., Immenschuh, S., Leffler, A., Ius, F., Haverich, A., Gottlieb, J., Haller, H., and Scheffner, I. (2022). Kidney injury after lung transplantation: Long-term mortality predicted by post-operative day-7 serum creatinine and few clinical factors. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0265002"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e14568","DOI":"10.1111\/ctr.14568","article-title":"Insights into early postoperative acute kidney injury following lung transplantation","volume":"36","author":"Botros","year":"2022","journal-title":"Clin. Transplant."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1097\/TP.0000000000003814","article-title":"Intraoperative Hypoxia Independently Associated With the Development of Acute Kidney Injury Following Bilateral Orthotopic Lung Transplantation","volume":"106","author":"Knight","year":"2022","journal-title":"Transplantation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.3389\/fimmu.2019.02975","article-title":"Labile Heme Aggravates Renal Inflammation and Complement Activation After Ischemia Reperfusion Injury","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1161\/CIRCULATIONAHA.110.008698","article-title":"Nitric oxide scavenging by red blood cell microparticles and cell-free hemoglobin as a mechanism for the red cell storage lesion","volume":"124","author":"Donadee","year":"2011","journal-title":"Circulation"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1858","DOI":"10.1056\/NEJMoa1707572","article-title":"Age of Red Cells for Transfusion and Outcomes in Critically Ill Adults","volume":"377","author":"Cooper","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1213\/ANE.0000000000002437","article-title":"Transfusion of Older Red Blood Cells Increases the Risk of Acute Kidney Injury After Orthotopic Liver Transplantation: A Propensity Score Analysis","volume":"127","author":"Wang","year":"2018","journal-title":"Anesth. Analg."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"106386","DOI":"10.1016\/j.prostaglandins.2019.106386","article-title":"Dietary omega-3 PUFA improved tubular function after ischemia induced acute kidney injury in mice but did not attenuate impairment of renal function","volume":"146","author":"Rund","year":"2020","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"F881","DOI":"10.1152\/ajprenal.00519.2016","article-title":"Renal ischemia-reperfusion injury causes hypertension and renal perfusion impairment in the CD1 mice which promotes progressive renal fibrosis","volume":"314","author":"Greite","year":"2018","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"F563","DOI":"10.1152\/ajprenal.00078.2020","article-title":"Early antihypertensive treatment and ischemia-induced acute kidney injury","volume":"319","author":"Greite","year":"2020","journal-title":"Am. J. Physiol. Renal. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1111\/tri.13812","article-title":"Impact of unilateral diaphragm elevation on postoperative outcomes in bilateral lung transplantation\u2014A retrospective single-center study","volume":"34","author":"Draeger","year":"2021","journal-title":"Transpl. Int."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.healun.2015.08.016","article-title":"Five-year experience with intraoperative extracorporeal membrane oxygenation in lung transplantation: Indications and midterm results","volume":"35","author":"Ius","year":"2016","journal-title":"J. Heart Lung Transplant."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/ki.2013.378","article-title":"Reading between the (guide)lines\u2014The KDIGO practice guideline on acute kidney injury in the individual patient","volume":"85","author":"Okusa","year":"2014","journal-title":"Kidney Int."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/21\/13272\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:06:52Z","timestamp":1760144812000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/21\/13272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,31]]},"references-count":41,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["ijms232113272"],"URL":"https:\/\/doi.org\/10.3390\/ijms232113272","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,31]]}}}