{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T18:01:54Z","timestamp":1787508114892,"version":"build-2736575974"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Delayed graft function (DGF) leads to a reduced graft survival. Donors\u2019 features have been always considered as key pathogenic factors in this setting. The aim of our study was to evaluate the recipients\u2019 characteristics in the development of DGF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We enrolled 932 kidney graft recipients from 466 donors; 226 recipients experienced DGF. In 290 donors, both recipients presented with early graft function (EGF, group A), in 50 both recipients experienced DGF (group B), and in 126 one recipient presented with DGF and the other with EGF (group C). In group C, we selected 7 couples of DGF\/EGF recipients and we evaluated the transcriptomic profile by microarray on circulating mononuclear cells harvested before transplantation. Results were validated by qPCR in an independent group of 25 EGF\/DGF couples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>In the whole study group, DGF was associated with clinical characteristics related to both donors and recipient. In group C, DGF was significantly associated with body mass index, hemodialysis, and number of mismatches. In the same group, we identified 411 genes differently expressed before transplantation between recipients discordant for the transplant outcome. Those genes were involved in immune dysfunction and inflammation. In particular, we observed a significant increase in DGF patients in the expression of C\u2013C chemokine receptor type 2 (CCR2), the monocyte chemoattractant protein-1 (MCP-1) receptor. CCR-2 upregulation was confirmed in an independent cohort of patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results suggest that recipients\u2019 clinical\/immunological features, potentially modulated by dialysis, are associated with the development of DGF independently of donors\u2019 features.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2022.804762","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T01:48:34Z","timestamp":1647395314000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Pre-Transplant Expression of CCR-2 in Kidney Transplant Recipients Is Associated With the Development of Delayed Graft Function"],"prefix":"10.3389","volume":"13","author":[{"given":"Paola","family":"Pontrelli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Simone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Rascio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Pesce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Conserva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Infante","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Castellano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Sallustio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Fiorentino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Zaza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gallone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Battaglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Ditonno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Stallone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loreto","family":"Gesualdo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Grandaliano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e3182a19348","article-title":"Defining Delayed Graft Function After Renal Transplantation: Simplest Is Best","volume":"96","author":"Mallon","year":"2013","journal-title":"Transplantation"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2010.03179.x","article-title":"A Risk Prediction Model for Delayed Graft Function in the Current Era of Deceased Donor Renal Transplantation","volume":"10","author":"Irish","year":"2010","journal-title":"Am J Transplant"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2995","DOI":"10.1093\/ndt\/gfn158","article-title":"Marked Variation in the Definition and Diagnosis of Delayed Graft Function: A Systematic Review","volume":"23","author":"Yarlagadda","year":"2008","journal-title":"Nephrol Dial Transpl"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/ctr.12832","article-title":"Prediction, Prevention, and Management of Delayed Graft Function: Where Are We Now","volume":"30","author":"Nashan","year":"2016","journal-title":"Clin Transplant"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfn667","article-title":"Association Between Delayed Graft Function and Allograft and Patient Survival: A Systematic Review and Meta-Analysis","volume":"24","author":"Yarlagadda","year":"2009","journal-title":"Nephrol Dial Transpl"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2016.01.028","article-title":"The Risk of Allograft Failure and the Survival Benefit of Kidney Transplantation are Complicated by Delayed Graft Function","volume":"89","author":"Gill","year":"2016","journal-title":"Kidney Int"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03754.x","article-title":"Delayed Graft Function in the Kidney Transplant","volume":"11","author":"Siedlecki","year":"2011","journal-title":"Am J Transplant"},{"key":"B8","doi-asserted-by":"publisher","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"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17406-0","article-title":"Delayed Graft Function in Kidney Transplantation","volume":"364","author":"Perico","year":"2004","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"253","DOI":"10.3390\/jcm9010253","article-title":"Ischemia and Reperfusion Injury in Kidney Transplantation: Relevant Mechanisms in Injury and Repair","volume":"9","author":"Nieuwenhuijs-Moeke","year":"2020","journal-title":"J Clin Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"100629","DOI":"10.1016\/j.trre.2021.100629","article-title":"Emerging Biomarkers of Delayed Graft Function in Kidney Transplantation","volume":"35","author":"Mezzolla","year":"2021","journal-title":"Transplant Rev"},{"key":"B12","doi-asserted-by":"publisher","first-page":"5404","DOI":"10.3390\/ijms21155404","article-title":"Recent Advances on Biomarkers of Early and Late Kidney Graft Dysfunction","volume":"21","author":"Quaglia","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B13","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12911-015-0206-y","article-title":"Prediction of Delayed Graft Function After Kidney Transplantation: Comparison Between Logistic Regression and Machine Learning Methods","volume":"15","author":"Decruyenaere","year":"2015","journal-title":"BMC Med Inform Decis"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2014.188","article-title":"A Useful Scoring System for the Prediction and Management of Delayed Graft Function Following Kidney Transplantation From Cadaveric Donors","volume":"86","author":"Chapal","year":"2014","journal-title":"Kidney Int"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00235.x","article-title":"Delayed Graft Function Influences Renal Function But Not Survival","volume":"58","author":"Boom","year":"2000","journal-title":"Kidney Int"},{"key":"B16","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1002\/path.4553","article-title":"A Type I Interferon Signature Characterizes Chronic Antibody-Mediated Rejection in Kidney Transplantation","volume":"237","author":"Rascio","year":"2015","journal-title":"J Pathol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010020181","article-title":"The Anti-Fibrotic Effect of Mycophenolic Acid-Induced Neutral Endopeptidase","volume":"21","author":"Dell'Oglio","year":"2010","journal-title":"J Am Soc Nephrol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btt703","article-title":"Causal Analysis Approaches in Ingenuity Pathway Analysis","volume":"30","author":"Kr\u00e4mer","year":"2014","journal-title":"Bioinformatics"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2004070621","article-title":"Coagulation Cascade Activation Causes CC Chemokine Receptor-2 Gene Expression and Mononuclear Cell Activation in Hemodialysis Patients","volume":"16","author":"Pertosa","year":"2005","journal-title":"J Am Soc Nephrol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0b013e318209f22b","article-title":"Recipient Risk Factors Associated With Delayed Graft Function: A Paired Kidney Analysis","volume":"91","author":"Doshi","year":"2011","journal-title":"Transplantation"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1097\/MOT.0000000000000709","article-title":"Innate Immunity in Ischemia-Reperfusion Injury and Graft Rejection","volume":"24","author":"Nakamura","year":"2019","journal-title":"Curr Opin Organ Tran"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012060560","article-title":"Renal Ischemia-Reperfusion Injury Amplifies the Humoral Immune Response","volume":"24","author":"Fuquay","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1097\/TP.0000000000000942","article-title":"Pre-Transplant Recipient Circulating CD4+CD127lo\/- Tumor Necrosis Factor Receptor 2+ Regulatory T Cells: A Surrogate of Regulatory T Cell-Suppressive Function and Predictor of Delayed and Slow Graft Function After Kidney Transplantation","volume":"100","author":"Nguyen","year":"2016","journal-title":"Transplantation"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfm804","article-title":"Dialysis-Related Systemic Microinflammation Is Associated With Specific Genomic Patterns","volume":"23","author":"Zaza","year":"2008","journal-title":"Nephrol Dial Transpl"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2741\/2990","article-title":"Roles of Chemokines in Renal Ischemia\/Reperfusion Injury","volume":"13","author":"Furuichi","year":"2008","journal-title":"Front Biosci"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010060641","article-title":"MCP-1 Gene Activation Marks Acute Kidney Injury","volume":"22","author":"Munshi","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2017.03.007","article-title":"Associations Between Deceased-Donor Urine MCP-1 and Kidney Transplant Outcomes","volume":"2","author":"Mansour","year":"2017","journal-title":"Kidney Int Rep"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2011.03755.x","article-title":"Renovascular Resistance of Machine-Perfused DCD Kidneys is Associated With Primary Nonfunction","volume":"11","author":"de Vries","year":"2011","journal-title":"Am J Transplant"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1111\/j.1744-9987.2009.00658.x","article-title":"C-C Chemokine Receptor 2 Expression by Circulating Monocytes Influences Atherosclerosis in Patients on Chronic Hemodialysis","volume":"13","author":"Okumoto","year":"2009","journal-title":"Ther Apher Dial"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00381.2009","article-title":"Uremia Impacts Renal Inflammatory Cytokine Gene Expression in the Setting of Experimental Acute Kidney Injury","volume":"297","author":"Zager","year":"2009","journal-title":"Am J Physiol-Renal"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.042501","article-title":"Endothelial Cell-Derived Interleukin-18 Released During Ischemia Reperfusion Injury Selectively Expands T Peripheral Helper Cells to Promote Alloantibody Production","volume":"141","author":"Liu","year":"2020","journal-title":"Circulation"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-014-1119-y","article-title":"Predictive Model for Delayed Graft Function Based on Easily Available Pre-Renal Transplant Variables","volume":"10","author":"Zaza","year":"2015","journal-title":"Intern Emerg Med"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.804762\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T01:48:36Z","timestamp":1647395316000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.804762\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,16]]},"references-count":32,"alternative-id":["10.3389\/fimmu.2022.804762"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.804762","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,16]]},"article-number":"804762"}}