{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T16:05:28Z","timestamp":1780329928174,"version":"3.54.1"},"reference-count":34,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCDD"],"abstract":"<jats:p>Circulating cell-free DNA (cfDNA) is released during tissue injury and systemic inflammation, but its association with postoperative organ injury following pediatric cardiac surgery remains incompletely defined. We evaluated the relationship between early postoperative cfDNA levels and acute kidney injury (AKI) and biochemical hepatic injury in children undergoing open-heart surgery with cardiopulmonary bypass (CPB). This retrospective observational cohort study included 50 pediatric patients (&lt;18 years) who underwent CPB at a tertiary congenital heart center between 2017 and 2018. Plasma cfDNA concentrations were measured perioperatively, with the 6 h postoperative value analyzed as an early biomarker window. AKI was classified using Kidney Disease: Improving Global Outcomes criteria, and hepatic injury was assessed using serial liver enzyme measurements. cfDNA levels increased significantly within 6 h after CPB and were higher in patients with more severe AKI. Six-hour cfDNA concentrations correlated with postoperative creatinine, urea, alanine aminotransferase, and aspartate aminotransferase. In multivariable regression analyses adjusting for cardiopulmonary bypass duration, aortic cross-clamp time, and preoperative oxygen saturation, cfDNA at 6 h remained independently associated with AKI severity and peak liver enzyme levels. These exploratory findings suggest that early postoperative cfDNA elevation is associated with AKI severity and biochemical hepatic injury after pediatric cardiac surgery with CPB. Larger prospective studies are needed to determine its independent predictive value and clinical utility.<\/jats:p>","DOI":"10.3390\/jcdd13060235","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:07:52Z","timestamp":1780326472000},"page":"235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early Postoperative Cell-Free DNA Reflects Renal and Hepatic Injury After Pediatric Cardiac Surgery"],"prefix":"10.3390","volume":"13","author":[{"given":"Hiba","family":"Abuelhija","sequence":"first","affiliation":[{"name":"Section of Pediatric Critical Care, Hadassah University Medical Center, Ein Kerem, POB 12000, Jerusalem 9112001, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"},{"name":"Cardiac Intensive Care Unit, Heart and Lung Directorate, Great Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3BH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asaf","family":"Mandel","sequence":"additional","affiliation":[{"name":"Section of Pediatric Critical Care, Hadassah University Medical Center, Ein Kerem, POB 12000, Jerusalem 9112001, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salmas","family":"Watad","sequence":"additional","affiliation":[{"name":"Section of Pediatric Critical Care, Hadassah University Medical Center, Ein Kerem, POB 12000, Jerusalem 9112001, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai","family":"Zemmour","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"},{"name":"Department of Pediatrics, Hadassah University Medical Center, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0961-8777","authenticated-orcid":false,"given":"Eitan","family":"Keizman","sequence":"additional","affiliation":[{"name":"Pediatric and Congenital Cardiac Surgery, Edmond J. Safra International Congenital Heart Center, The Edmond and Lily Safra Children\u2019s Hospital, Tel Hashomer, Ramat Gan 52621, Israel"},{"name":"Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Division of Cardiac Surgery, Department of Surgery, Columbia University, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Mishaly","sequence":"additional","affiliation":[{"name":"Pediatric and Congenital Cardiac Surgery, Edmond J. Safra International Congenital Heart Center, The Edmond and Lily Safra Children\u2019s Hospital, Tel Hashomer, Ramat Gan 52621, Israel"},{"name":"Gray Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Arfi Levy","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"},{"name":"Pediatric and Congenital Cardiac Surgery, Hadassah University Medical Center, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alain E.","family":"Serraf","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"},{"name":"Pediatric and Congenital Cardiac Surgery, Hadassah University Medical Center, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4575-3888","authenticated-orcid":false,"given":"Uri","family":"Pollak","sequence":"additional","affiliation":[{"name":"Section of Pediatric Critical Care, Hadassah University Medical Center, Ein Kerem, POB 12000, Jerusalem 9112001, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"ref_1","first-page":"1659","article-title":"DNA fragments in the blood plasma of cancer patients: Quantitations and evidence for their origin from apoptotic and necrotic cells","volume":"61","author":"Jahr","year":"2001","journal-title":"Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1002\/path.2960","article-title":"Plasma nucleic acid analysis by massively parallel sequencing: Pathological insights and diagnostic implications","volume":"225","author":"Lo","year":"2011","journal-title":"J. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1373\/clinchem.2007.101030","article-title":"Cell-free plasma DNA as a predictor of outcome in severe sepsis and septic shock","volume":"54","author":"Saukkonen","year":"2008","journal-title":"Clin. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/nrc3066","article-title":"Cell-free nucleic acids as biomarkers in cancer patients","volume":"11","author":"Schwarzenbach","year":"2011","journal-title":"Nat. Rev. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1373\/49.4.562","article-title":"Prognostic use of circulating plasma nucleic acid concentrations in patients with acute stroke","volume":"49","author":"Rainer","year":"2003","journal-title":"Clin. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2301","DOI":"10.1016\/j.jacc.2011.08.017","article-title":"Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass","volume":"58","author":"Krawczeski","year":"2011","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1097\/00000542-200105000-00010","article-title":"Tissue injury and the inflammatory response to pediatric cardiac surgery with cardiopulmonary bypass: A descriptive study","volume":"94","author":"Chew","year":"2001","journal-title":"Anesthesiology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1016\/j.jtcvs.2003.11.027","article-title":"Cardiopulmonary bypass elicits a prominent innate immune response in children with congenital heart disease","volume":"127","author":"Stocker","year":"2004","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1186\/s12967-023-04255-8","article-title":"Novel inflammatory mediator profile observed during pediatric heart surgery with cardiopulmonary bypass and continuous ultrafiltration","volume":"21","author":"Bierer","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.jtcvs.2011.06.021","article-title":"Congenital heart surgery in infants: Effects of acute kidney injury on outcomes","volume":"143","author":"Blinder","year":"2012","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1097\/CCM.0b013e31821201d3","article-title":"Incidence, risk factors, and outcomes of acute kidney injury after pediatric cardiac surgery: A prospective multicenter study","volume":"39","author":"Li","year":"2011","journal-title":"Crit. Care Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1093\/ndt\/gfp392","article-title":"Comparison of methods for estimating glomerular filtration rate in critically ill patients with acute kidney injury","volume":"25","author":"Bouchard","year":"2010","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Kehl, T., Biermann, D., Briem-Richter, A., Schoen, G., Olfe, J., Sachweh, J.S., Fischer, L., Schaefer, H., Kozlik-Feldmann, R., and Gottschalk, U. (2021). Impact of hepatopathy in pediatric patients after surgery for complex congenital heart disease. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0248776"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Itagaki, K., Kaczmarek, E., Lee, Y.T., Tang, I.T., Isal, B., Adibnia, Y., Sandler, N., Grimm, M.J., Segal, B.H., and Otterbein, L.E. (2015). Mitochondrial DNA Released by Trauma Induces Neutrophil Extracellular Traps. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0120549"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0009-8981(01)00653-2","article-title":"Plasma DNA, prediction and post-traumatic complications","volume":"313","author":"Rainer","year":"2001","journal-title":"Clin. Chim. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nature08780","article-title":"Circulating mitochondrial DAMPs cause inflammatory responses to injury","volume":"464","author":"Zhang","year":"2010","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nature10992","article-title":"Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure","volume":"485","author":"Oka","year":"2012","journal-title":"Nature"},{"key":"ref_18","first-page":"2794364","article-title":"Perioperative Elevation in Cell-Free DNA Levels in Patients Undergoing Cardiac Surgery: Possible Contribution of Neutrophil Extracellular Traps to Perioperative Renal Dysfunction","volume":"2016","author":"Qi","year":"2016","journal-title":"Anesthesiol. Res. Pract."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Nakahira, K., Kyung, S.Y., Rogers, A.J., Gazourian, L., Youn, S., Massaro, A.F., Quintana, C., Osorio, J.C., Wang, Z., and Zhao, Y. (2013). Circulating mitochondrial DNA in patients in the ICU as a marker of mortality: Derivation and validation. PLoS Med., 10.","DOI":"10.1371\/journal.pmed.1001577"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.athoracsur.2022.10.027","article-title":"Nuclear Cell-Free DNA Predicts Adverse Events After Pediatric Cardiothoracic Surgery","volume":"116","author":"Tanem","year":"2023","journal-title":"Ann. Thorac. Surg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s12265-022-10295-0","article-title":"Novel cfDNA Methylation Biomarkers Reveal Delayed Cardiac Cell Death after Open-heart Surgery","volume":"16","author":"Pollak","year":"2023","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/s41467-018-03961-y","article-title":"Non-invasive detection of human cardiomyocyte death using methylation patterns of circulating DNA","volume":"9","author":"Zemmour","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/s41398-018-0264-x","article-title":"Cell-free DNA release under psychosocial and physical stress conditions","volume":"8","author":"Hummel","year":"2018","journal-title":"Transl. Psychiatry"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.jtcvs.2021.10.066","article-title":"Elevated nuclear and mitochondrial cell-free deoxyribonucleic acid measurements are associated with death after infant cardiac surgery","volume":"164","author":"Scott","year":"2022","journal-title":"J. Thorac. Cardiovasc. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"19624","DOI":"10.1038\/s41598-023-46663-2","article-title":"Cell-free DNA as diagnostic and prognostic biomarkers for adult sepsis: A systematic review and meta-analysis","volume":"13","author":"Charoensappakit","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Duvvuri, B., and Lood, C. (2019). Cell-Free DNA as a Biomarker in Autoimmune Rheumatic Diseases. Front Immunol., 10.","DOI":"10.3389\/fimmu.2019.00502"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1080\/15384047.2019.1598759","article-title":"Life and death of circulating cell-free DNA","volume":"20","author":"Kustanovich","year":"2019","journal-title":"Cancer Biol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17478","DOI":"10.1038\/s41598-020-74288-2","article-title":"Cell-free DNA in plasma as an essential immune system regulator","volume":"10","author":"Korabecna","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Wan, D., Jiang, W., and Hao, J. (2020). Research Advances in How the cGAS-STING Pathway Controls the Cellular Inflammatory Response. Front Immunol., 11.","DOI":"10.3389\/fimmu.2020.00615"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"120874","DOI":"10.1016\/j.lfs.2022.120874","article-title":"TLR9: A friend or a foe","volume":"307","author":"Saber","year":"2022","journal-title":"Life Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Qi, T., Pan, M., Shi, H., Wang, L., Bai, Y., and Ge, Q. (2023). Cell-Free DNA Fragmentomics: The Novel Promising Biomarker. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021503"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.tig.2023.01.004","article-title":"Bridging biological cfDNA features and machine learning approaches","volume":"39","author":"Moser","year":"2023","journal-title":"Trends Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.molmed.2020.01.012","article-title":"Cell-Free DNA and Apoptosis: How Dead Cells Inform About the Living","volume":"26","author":"Heitzer","year":"2020","journal-title":"Trends Mol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.tig.2021.04.005","article-title":"The Nexus of cfDNA and Nuclease Biology","volume":"37","author":"Han","year":"2021","journal-title":"Trends Genet."}],"container-title":["Journal of Cardiovascular Development and Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2308-3425\/13\/6\/235\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T15:37:46Z","timestamp":1780328266000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2308-3425\/13\/6\/235"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,31]]},"references-count":34,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["jcdd13060235"],"URL":"https:\/\/doi.org\/10.3390\/jcdd13060235","relation":{},"ISSN":["2308-3425"],"issn-type":[{"value":"2308-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,31]]}}}