{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:02:04Z","timestamp":1787313724593,"version":"build-2736575974"},"reference-count":106,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T00:00:00Z","timestamp":1621555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Currently, kidney transplantation is widely accepted as the renal replacement therapy allowing for the best quality of life and longest survival of patients developing end-stage renal disease. However, chronic transplant rejection, recurrence of previous kidney disease or newly acquired conditions, or immunosuppressive drug toxicity often lead to a deterioration of kidney allograft function over time. Complement components play an important role in the pathogenesis of kidney allograft impairment. Most studies on the role of complement in kidney graft function focus on humoral rejection; however, complement has also been associated with cell mediated rejection, post-transplant thrombotic microangiopathy, the recurrence of several glomerulopathies in the transplanted kidney, and transplant tolerance. Better understanding of the complement involvement in the transplanted kidney damage has led to the development of novel therapies that inhibit complement components and improve graft survival. The analysis of functional complotypes, based on the genotype of both graft recipient and donor, may become a valuable tool for assessing the risk of acute transplant rejection. The review summarizes current knowledge on the pathomechanisms of complement activation following kidney transplantation and the resulting diagnostic and therapeutic possibilities.<\/jats:p>","DOI":"10.3390\/biom11060773","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T13:15:15Z","timestamp":1621602915000},"page":"773","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Complement Components in the Diagnosis and Treatment after Kidney Transplantation\u2014Is There a Missing Link?"],"prefix":"10.3390","volume":"11","author":[{"given":"Ma\u0142gorzata","family":"Kielar","sequence":"first","affiliation":[{"name":"St. Louis Regional Children\u2019s Hospital, Medical Diagnostic Laboratory with a Bacteriology Laboratory, Strzelecka 2 St., 31-503 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6617-0852","authenticated-orcid":false,"given":"Agnieszka","family":"Gala-B\u0142\u0105dzi\u0144ska","sequence":"additional","affiliation":[{"name":"Medical College of Rzesz\u00f3w University, Institute of Medical Sciences, Kopisto 2A Avn., 35-310 Rzesz\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3667-857X","authenticated-orcid":false,"given":"Paulina","family":"Dumnicka","sequence":"additional","affiliation":[{"name":"Jagiellonian University Medical College, Faculty of Pharmacy, Department of Medical Diagnostics, Medyczna 9 St., 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3478-0108","authenticated-orcid":false,"given":"Piotr","family":"Ceranowicz","sequence":"additional","affiliation":[{"name":"Jagiellonian University Medical College, Faculty of Medicine, Department of Physiology, Grzeg\u00f3rzecka 16 St., 31-531 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kapusta","sequence":"additional","affiliation":[{"name":"Jagiellonian University Medical College, Faculty of Medicine, Chair of Clinical Biochemistry, Department of Diagnostics, Kopernika 15A St., 31-501 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Naumnik","sequence":"additional","affiliation":[{"name":"Medical University of Bia\u0142ystok, Faculty of Medicine, 1st Department of Nephrology and Transplantation with Dialysis Unit, \u017burawia 14 St., 15-540 Bia\u0142ystok, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grzegorz","family":"Kubiak","sequence":"additional","affiliation":[{"name":"Catholic University of Leuven, Department of Cardiovascular Diseases, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Ku\u017aniewski","sequence":"additional","affiliation":[{"name":"Jagiellonian University Medical College, Faculty of Medicine, Chair and Department of Nephrology, Jakubowskiego 2 St., 30-688 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Ku\u015bnierz-Cabala","sequence":"additional","affiliation":[{"name":"Jagiellonian University Medical College, Faculty of Medicine, Chair of Clinical Biochemistry, Department of Diagnostics, Kopernika 15A St., 31-501 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"ref_1","first-page":"382","article-title":"Diagnostic criteria of antibody-mediated rejection in kidney transplants","volume":"31","year":"2011","journal-title":"Nefrologia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1056\/NEJMra0902927","article-title":"Rejection of the Kidney Allograft","volume":"363","author":"Nankivell","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group (2009). KDIGO Clinical Practice Guideline for the Care of Kidney Transplant Recipients. Am. J. Transplant., 9, S1\u2013S155.","DOI":"10.1111\/j.1600-6143.2009.02834.x"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1093\/ndt\/gfr169","article-title":"Endorsement of the Kidney Disease Improving Global Outcomes (KDIGO) guidelines on kidney transplantation: A European Renal Best Practice (ERBP) position statement","volume":"26","author":"Heemann","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/ajt.14625","article-title":"The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell\u2013mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials","volume":"18","author":"Haas","year":"2018","journal-title":"Am. J. Transplant."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/ni.3858","article-title":"Novel mechanisms and functions of complement","volume":"18","author":"Hajishengallis","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1097\/MOT.0000000000000706","article-title":"When rubber meets the road: How innate features of adaptive immune cells play critical roles in transplant alloimmunity","volume":"24","author":"Morris","year":"2019","journal-title":"Curr. Opin. Organ Transplant."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.semcdb.2017.11.022","article-title":"Complement components as promoters of immunological tolerance in dendritic cells","volume":"85","author":"Luque","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fmed.2017.00066","article-title":"Complement in kidney transplantation","volume":"4","author":"Cernoch","year":"2017","journal-title":"Front. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1093\/ndt\/gfq717","article-title":"Local renal complement C3 induction by donor brain death is associated with reduced renal allograft function after transplantation","volume":"26","author":"Damman","year":"2011","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1097\/MOT.0b013e32833b9cb7","article-title":"Complement in organ transplantation","volume":"15","author":"Asgari","year":"2010","journal-title":"Curr. Opin. Organ Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1556\/EuJMI.2.2012.2.2","article-title":"The complement system: History, pathways, cascade and inhibitors","volume":"2","author":"Nesargikar","year":"2012","journal-title":"Eur. J. Microbiol. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"317","DOI":"10.2119\/molmed.2010.00149","article-title":"New insights of an old defense system: Structure, function, and clinical relevance of the complement system","volume":"17","author":"Ehrnthaller","year":"2011","journal-title":"Mol. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2019.02380","article-title":"The Role of Complement in Organ Transplantation","volume":"10","author":"Grafals","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/nm0602-582","article-title":"Local synthesis of complement component C3 regulates acute renal transplant rejection","volume":"8","author":"Pratt","year":"2002","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2020.00734","article-title":"Inflammaging and Complement System: A Link Between Acute Kidney Injury and Chronic Graft Damage","volume":"11","author":"Franzin","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1111\/imr.12852","article-title":"Complement and human T cell metabolism: Location, location, location","volume":"295","author":"West","year":"2020","journal-title":"Immunol. Rev."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.molimm.2017.05.012","article-title":"Intracellular complement\u2014The complosome\u2014In immune cell regulation","volume":"89","author":"Arbore","year":"2017","journal-title":"Mol. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Kolev, M., and Kemper, C. (2017). Keeping it all going-complement meets metabolism. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00001"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1097\/MOT.0000000000000724","article-title":"Latest developments in living kidney donation","volume":"25","author":"Hilbrands","year":"2020","journal-title":"Curr. Opin. Organ Transplant."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1097\/TP.0000000000000500","article-title":"Hypoxia and complement-and-coagulation pathways in the deceased organ donor as the major target for intervention to improve renal allograft outcome","volume":"99","author":"Damman","year":"2015","journal-title":"Transplantation"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1755-1536-7-16","article-title":"The role of complement in the pathogenesis of renal ischemia-reperfusion injury and fibrosis","volume":"7","author":"Danobeitia","year":"2014","journal-title":"Fibrogenesis Tissue Repair"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/nri2215","article-title":"How dying cells alert the immune system to danger","volume":"8","author":"Kono","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1172\/JCI8621","article-title":"Predominant role for C5b-9 in renal ischemia\/reperfusion injury","volume":"105","author":"Zhou","year":"2000","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.coi.2007.07.007","article-title":"Graft-derived complement as a mediator of transplant injury","volume":"19","author":"Zhou","year":"2007","journal-title":"Curr. Opin. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/S0952-7915(03)00100-6","article-title":"Role of the complement system in rejection","volume":"15","author":"Sacks","year":"2003","journal-title":"Curr. Opin. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcell.2021.624025","article-title":"Complement Receptors and Their Role in Leukocyte Recruitment and Phagocytosis","volume":"9","author":"Vandendriessche","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s00109-009-0442-7","article-title":"Functions of C5a receptors","volume":"87","author":"Ward","year":"2009","journal-title":"J. Mol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"F35","DOI":"10.1152\/ajprenal.00060.2017","article-title":"Complement C5a receptors C5L2 and C5aR in renal fibrosis","volume":"314","author":"Martin","year":"2018","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2571","DOI":"10.1681\/ASN.2017010079","article-title":"Complement recognition pathways in renal transplantation","volume":"28","author":"Nauser","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1159\/000494014","article-title":"Is early complement activation in renal transplantation associated with later graft outcome?","volume":"43","author":"Bobka","year":"2018","journal-title":"Kidney Blood Press. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1111\/j.1600-6143.2009.02799.x","article-title":"Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure","volume":"9","author":"Einecke","year":"2009","journal-title":"Am. J. Transplant."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5525","DOI":"10.4049\/jimmunol.1501686","article-title":"The Complement System and Antibody-Mediated Transplant Rejection","volume":"195","author":"Stites","year":"2015","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/j.1600-6143.2010.03415.x","article-title":"Inflammation lesions in kidney transplant biopsies: Association with survival is due to the underlying diseases","volume":"11","author":"Mengel","year":"2011","journal-title":"Am. J. Transplant."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1111\/j.1600-6143.2011.03840.x","article-title":"Understanding the causes of kidney transplant failure: The dominant role of antibody-mediated rejection and nonadherence","volume":"12","author":"Mengel","year":"2012","journal-title":"Am. J. Transplant."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1056\/NEJMoa1302506","article-title":"Complement-binding anti-HLA antibodies and kidney-allograft survival","volume":"369","author":"Loupy","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Loupy, A., Haas, M., Roufosse, C., Naesens, M., Adam, B., Afrouzian, M., Akalin, E., Alachkar, N., Bagnasco, S., and Becker, J.U. (2020). The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell\u2013 and antibody-mediated rejection. Am. J. Transplant., 1\u201314.","DOI":"10.1111\/ajt.15898"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/ki.2011.497","article-title":"Pros and cons for C4d as a biomarker","volume":"81","author":"Cohen","year":"2012","journal-title":"Kidney Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1097\/MOT.0b013e3283352a50","article-title":"Endothelial transcripts uncover a previously unknown phenotype: C4d-negative antibody-mediated rejection","volume":"15","author":"Sis","year":"2010","journal-title":"Curr. Opin. Organ Transplant."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2459","DOI":"10.1111\/j.1600-6143.2009.02819.x","article-title":"Effect of antibodies on endothelium: Minireview","volume":"9","author":"Zhang","year":"2009","journal-title":"Am. J. Transplant."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1399-3046.2011.01599.x","article-title":"Complement-fixing donor-specific antibodies identified by a novel C1q assay are associated with allograft loss","volume":"16","author":"Sutherland","year":"2012","journal-title":"Pediatr. Transplant."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1097\/TP.0000000000000699","article-title":"C1q Binding Activity of De Novo Donor-specific HLA Antibodies in Renal Transplant Recipients With and Without Antibody-mediated Rejection","volume":"99","author":"Yell","year":"2015","journal-title":"Transplantation"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.kint.2018.03.015","article-title":"Complement-binding anti-HLA antibodies are independent predictors of response to treatment in kidney recipients with antibody-mediated rejection","volume":"94","author":"Viglietti","year":"2018","journal-title":"Kidney Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1681\/ASN.2013101144","article-title":"Detection of C3d-binding donor-specific anti-HLA antibodies at diagnosis of humoral rejection predicts renal graft loss","volume":"26","author":"Sicard","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_45","first-page":"1","article-title":"Age-associated decrease in de novo donor-specific antibodies in renal transplant recipients reflects changing humoral immunity","volume":"16","author":"Schalk","year":"2019","journal-title":"Immun. Ageing"},{"key":"ref_46","first-page":"449","article-title":"Deduction of the fraction of immunologic and nonimmunologic failure in cadaver donor transplants","volume":"1","author":"Terasaki","year":"2003","journal-title":"Clin. Transpl."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.humimm.2016.05.021","article-title":"Pathogenesis of non-HLA antibodies in solid organ transplantation: Where do we stand?","volume":"77","author":"Delville","year":"2016","journal-title":"Hum. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2018.02548","article-title":"T cell allorecognition pathways in solid organ transplantation","volume":"9","author":"Siu","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_49","first-page":"13","article-title":"The immune response to kidney allograft. Part I: The role of MHC antigens, antigen-presenting cells, and lymphocytes in alloantigen recognition; two-signal activation of T cells","volume":"61","author":"Kusztal","year":"2007","journal-title":"Postepy Hig. Med. Dosw."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.4049\/jimmunol.172.3.1341","article-title":"Cutting Edge: Distinct TCR- and CD28-Derived Signals Regulate CD95L, Bcl-x L, and the Survival of Primary T Cells","volume":"172","author":"Kerstan","year":"2004","journal-title":"J. Immunol."},{"key":"ref_51","first-page":"21","article-title":"The immune response to kidney allograft. Part II: The role of costimulatory and accessory molecules in T-cell activation; The effector phase of response","volume":"61","author":"Kusztal","year":"2007","journal-title":"Postepy Hig. Med. Dosw."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.immuni.2008.02.001","article-title":"Locally Produced Complement Fragments C5a and C3a Provide Both Costimulatory and Survival Signals to Naive CD4+ T Cells","volume":"28","author":"Strainic","year":"2008","journal-title":"Immunity"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1182\/blood-2007-06-095018","article-title":"Local production and activation of complement up-regulates the allostimulatory function of dendritic cells through C3a-C3aR interaction","volume":"111","author":"Peng","year":"2008","journal-title":"Blood"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1002\/eji.201646703","article-title":"Properdin and factor H production by human dendritic cells modulates their T-cell stimulatory capacity and is regulated by IFN-\u03b3","volume":"47","author":"Dixon","year":"2017","journal-title":"Eur. J. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"335","DOI":"10.5414\/CNP67335","article-title":"De novo thrombotic microangiopathy. An underrated complication of renal transplantation","volume":"67","author":"Ponticelli","year":"2007","journal-title":"Clin. Nephrol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.trre.2017.10.001","article-title":"De novo thrombotic microangiopathy after kidney transplantation","volume":"32","author":"Garg","year":"2018","journal-title":"Transplant. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1097\/MNH.0b013e3283378f25","article-title":"Thrombotic microangiopathy: New insights","volume":"19","author":"Benz","year":"2010","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1111\/j.1600-6143.2004.00428.x","article-title":"Increased risk of thrombotic microangiopathy in patients receiving a cyclosporin-sirolimus combination","volume":"4","author":"Fortin","year":"2004","journal-title":"Am. J. Transplant."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1016\/j.transproceed.2014.07.062","article-title":"Everolimus, cyclosporine, and thrombotic microangiopathy: Clinical role and preventive tools in renal transplantation","volume":"46","author":"Nava","year":"2014","journal-title":"Transplant. Proc."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1111\/j.1600-6143.2008.02297.x","article-title":"Complement mutation-associated de novo thrombotic microangiopathy following kidney transplantation","volume":"8","author":"Lionet","year":"2008","journal-title":"Am. J. Transplant."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/his.13855","article-title":"Clinical\u2013pathological correlations in post-transplant thrombotic microangiopathy","volume":"75","author":"Broecker","year":"2019","journal-title":"Histopathology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1053\/j.ajkd.2015.03.040","article-title":"Glomerular Diseases Dependent on Complement Activation, Including Atypical Hemolytic Uremic Syndrome, Membranoproliferative Glomerulonephritis, and C3 Glomerulopathy: Core Curriculum 2015","volume":"66","author":"Noris","year":"2015","journal-title":"Am. J. Kidney Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/ki.2013.377","article-title":"C3 glomerulopathy: Consensus report","volume":"84","author":"Pickering","year":"2013","journal-title":"Kidney Int."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.kint.2020.05.053","article-title":"Practical management of C3 glomerulopathy and Ig-mediated MPGN: Facts and uncertainties","volume":"98","author":"Fakhouri","year":"2020","journal-title":"Kidney Int."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.kint.2016.08.030","article-title":"Recent advances in our understanding of recurrent primary glomerulonephritis after kidney transplantation","volume":"91","author":"Cosio","year":"2017","journal-title":"Kidney Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMra1108178","article-title":"Membranoproliferative Glomerulonephritis\u2014A New Look at an Old Entity","volume":"366","author":"Sethi","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"632","DOI":"10.5500\/wjt.v6.i4.632","article-title":"Complement related kidney diseases: Recurrence after transplantation","volume":"6","author":"Salvadori","year":"2016","journal-title":"World J. Transplant."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1111\/aor.13551","article-title":"Tacrolimus: 20 years of use in adult kidney transplantation. What we should know about its nephrotoxicity","volume":"44","author":"Bentata","year":"2020","journal-title":"Artif. Organs"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"517","DOI":"10.3349\/ymj.2007.48.3.517","article-title":"Activation of intrarenal complement system in mouse model for chronic cyclosporine nephrotoxicity","volume":"48","author":"Kim","year":"2007","journal-title":"Yonsei Med. J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1681\/ASN.2012111064","article-title":"Cyclosporine induces endothelial cell release of complement-activating microparticles","volume":"24","author":"Renner","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1097\/00007890-201407151-02238","article-title":"Complement System and MAPK Signaling in Calcineurin-Inhibitor Induced Nephrotoxicity","volume":"98","author":"Neuwirt","year":"2014","journal-title":"Transplantation"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1002\/eji.201747135","article-title":"Calcineurin inhibitor-induced complement system activation via ERK1\/2 signalling is inhibited by SOCS-3 in human renal tubule cells","volume":"48","author":"Loeschenberger","year":"2018","journal-title":"Eur. J. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1097\/TP.0000000000003095","article-title":"Recommended Treatment for Antibody-mediated Rejection After Kidney Transplantation","volume":"104","author":"Schinstock","year":"2020","journal-title":"Transplantation"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1111\/ajt.13663","article-title":"C1 Inhibitor in Acute Antibody-Mediated Rejection Nonresponsive to Conventional Therapy in Kidney Transplant Recipients: A Pilot Study","volume":"16","author":"Viglietti","year":"2016","journal-title":"Am. J. Transplant."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1097\/TP.0000000000000592","article-title":"A Phase I\/II Placebo-Controlled Trial of C1-Inhibitor for Prevention of Antibody-Mediated Rejection in HLA Sensitized Patients","volume":"99","author":"Vo","year":"2015","journal-title":"Transplantation"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1097\/TP.0000000000002049","article-title":"The treatment of antibody-mediated rejection in kidney transplantation: An updated systematic review and meta-analysis","volume":"102","author":"Wan","year":"2018","journal-title":"Transplantation"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3468","DOI":"10.1111\/ajt.13871","article-title":"Plasma-Derived C1 Esterase Inhibitor for Acute Antibody-Mediated Rejection Following Kidney Transplantation: Results of a Randomized Double-Blind Placebo-Controlled Pilot Study","volume":"16","author":"Montgomery","year":"2016","journal-title":"Am. J. Transplant."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"126","DOI":"10.21037\/tau.2019.03.05","article-title":"Current protocols and outcomes of ABO-incompatible kidney transplantation based on a single-center experience","volume":"8","author":"Okumi","year":"2019","journal-title":"Transl. Androl. Urol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12882-015-0201-7","article-title":"Low dose of mycophenolate mofetil is enough in desensitized kidney transplantation using rituximab","volume":"16","author":"Baek","year":"2015","journal-title":"BMC Nephrol."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Chauhan, K., and Mehta, A.A. (2019). Rituximab in kidney disease and transplant. Anim. Model. Exp. Med., 76\u201382.","DOI":"10.1002\/ame2.12064"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1681\/ASN.2017070818","article-title":"A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection","volume":"29","author":"Eskandary","year":"2018","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e227","DOI":"10.1097\/TXD.0000000000000746","article-title":"Rituximab and Monitoring Strategies for Late Antibody-Mediated Rejection After Kidney Transplantation","volume":"3","author":"Parajuli","year":"2017","journal-title":"Transplant. Direct"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0224203","article-title":"Single fixed low-dose rituximab as induction therapy suppresses de novo donor-specific anti-HLA antibody production in ABO compatible living kidney transplant recipients","volume":"14","author":"Tomita","year":"2019","journal-title":"PLoS ONE"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/TXD.0000000000000923","article-title":"Low-dose Rituximab and Thymoglobulin Induction with Steroid-free Maintenance Immunosuppression and Protocol Biopsies Improves Long-term Patient and Graft Survival after Kidney Transplantation: Survival and Safety Outcomes in More Than 1100 Patients from a","volume":"5","author":"Pathak","year":"2019","journal-title":"Transplant. Direct"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1111\/j.1600-6143.2011.03757.x","article-title":"Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients","volume":"11","author":"Stegall","year":"2011","journal-title":"Am. J. Transplant."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Gonzalez Suarez, M.L., Thongprayoon, C., Mao, M.A., Leeaphorn, N., Bathini, T., and Cheungpasitporn, W. (2019). Outcomes of Kidney Transplant Patients with Atypical Hemolytic Uremic Syndrome Treated with Eculizumab: A Systematic Review and Meta-Analysis. J. Clin. Med., 8.","DOI":"10.3390\/jcm8070919"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2876","DOI":"10.1111\/ajt.15364","article-title":"Safety and efficacy of eculizumab in the prevention of antibody-mediated rejection in living-donor kidney transplant recipients requiring desensitization therapy: A randomized trial","volume":"19","author":"Marks","year":"2019","journal-title":"Am. J. Transplant."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1038\/ki.2014.423","article-title":"Efficacy and safety of eculizumab in atypical hemolytic uremic syndrome from 2-year extensions of phase 2 studies","volume":"87","author":"Licht","year":"2015","journal-title":"Kidney Int."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2169","DOI":"10.1056\/NEJMoa1208981","article-title":"Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome","volume":"368","author":"Legendre","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1111\/tri.13022","article-title":"Outcomes of patients with atypical haemolytic uraemic syndrome with native and transplanted kidneys treated with eculizumab: A pooled post hoc analysis","volume":"30","author":"Legendre","year":"2017","journal-title":"Transpl. Int."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1111\/ajt.14001","article-title":"Eculizumab Therapy for Chronic Antibody-Mediated Injury in Kidney Transplant Recipients: A Pilot Randomized Controlled Trial","volume":"17","author":"Kulkarni","year":"2017","journal-title":"Am. J. Transplant."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"4057","DOI":"10.1016\/j.molimm.2008.06.028","article-title":"Biological activities of C1 inhibitor","volume":"45","author":"Davis","year":"2008","journal-title":"Mol. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.molimm.2013.01.009","article-title":"The control of the complement lectin pathway activation revisited: Both C1-inhibitor and antithrombin are likely physiological inhibitors, While \u03b12-macroglobulin is not","volume":"54","year":"2013","journal-title":"Mol. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1097\/TP.0000000000000995","article-title":"Potential roles for C1 inhibitor in transplantation","volume":"100","author":"Berger","year":"2016","journal-title":"Transplantation"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1111\/ajt.14528","article-title":"Anti-C1s monoclonal antibody BIVV009 in late antibody-mediated kidney allograft rejection\u2014Results from a first-in-patient phase 1 trial","volume":"18","author":"Eskandary","year":"2018","journal-title":"Am. J. Transplant."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1056\/NEJMoa1612567","article-title":"IgG endopeptidase in highly sensitized patients undergoing transplantation","volume":"377","author":"Jordan","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13063-017-1972-x","article-title":"A double-blind randomised controlled investigation into the efficacy of Mirococept (APT070) for preventing ischaemia reperfusion injury in the kidney allograft (EMPIRIKAL): Study protocol for a randomised controlled trial","volume":"18","author":"Kassimatis","year":"2017","journal-title":"Trials"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1111\/bph.13388","article-title":"APT070 (mirococept), a membrane-localizing C3 convertase inhibitor, attenuates early human islet allograft damage in vitro and in vivo in a humanized mouse model","volume":"173","author":"Xiao","year":"2016","journal-title":"Br. J. Pharmacol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.it.2012.06.001","article-title":"The complotype: Dictating risk for inflammation and infection","volume":"33","author":"Harris","year":"2012","journal-title":"Trends Immunol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.smim.2016.04.007","article-title":"Complement\u2014Here, there and everywhere, but what about the transplanted organ?","volume":"28","author":"Montero","year":"2016","journal-title":"Semin. Immunol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2955","DOI":"10.1111\/ajt.14767","article-title":"A phase I\/II, double-blind, placebo-controlled study assessing safety and efficacy of C1 esterase inhibitor for prevention of delayed graft function in deceased donor kidney transplant recipients","volume":"18","author":"Jordan","year":"2018","journal-title":"Am. J. Transplant."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"109","DOI":"10.2215\/CJN.04840419","article-title":"Three-Year Outcomes of a Randomized, Double-Blind, Placebo-Controlled Study Assessing Safety and Efficacy of C1 Esterase Inhibitor for Prevention of Delayed Graft Function in Deceased Donor Kidney Transplant Recipients","volume":"15","author":"Huang","year":"2020","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"2014","DOI":"10.1056\/NEJMoa052825","article-title":"Influence of donor C3 allotype on late renal-transplantation outcome","volume":"354","author":"Brown","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5921","DOI":"10.4049\/jimmunol.1300847","article-title":"Cutting Edge: Receptors for C3a and C5a Modulate Stability of Alloantigen-Reactive Induced Regulatory T Cells","volume":"190","author":"Cravedi","year":"2013","journal-title":"J. Immunol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.kint.2015.11.025","article-title":"Polymorphisms in the lectin pathway of complement activation influence the incidence of acute rejection and graft outcome after kidney transplantation","volume":"89","author":"Golshayan","year":"2016","journal-title":"Kidney Int."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"8761","DOI":"10.1073\/pnas.1019338108","article-title":"Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk","volume":"108","author":"Heurich","year":"2011","journal-title":"Proc. Natl. Acad. Sci. 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