{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T01:12:25Z","timestamp":1788484345953,"version":"build-2803163510"},"reference-count":88,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T00:00:00Z","timestamp":1772668800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T00:00:00Z","timestamp":1776038400000},"content-version":"vor","delay-in-days":39,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100015406","name":"Tianjin Municipal Science and Technology Bureau","doi-asserted-by":"publisher","award":["24ZYCGSN01310"],"award-info":[{"award-number":["24ZYCGSN01310"]}],"id":[{"id":"10.13039\/501100015406","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82072222"],"award-info":[{"award-number":["82072222"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Open Fund of the Key Laboratory of Emergency Medical Rescue Key Technology and Equipment, Ministry of Emergency Management","award":["YJBKFKT202419"],"award-info":[{"award-number":["YJBKFKT202419"]}]},{"name":"Tianjin Municipal Key Medical Disciplines (Specialties) Construction Program","award":["TJYXZDXK-3-009C"],"award-info":[{"award-number":["TJYXZDXK-3-009C"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Nephrol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The transition from acute kidney injury (AKI) to chronic kidney disease (CKD) remains a major clinical challenge and contributes to substantial morbidity and mortality. Interleukin-4 (IL-4), a key cytokine in T helper 2 (Th2) immunity, appears to influence this trajectory in a context-dependent manner. In acute injury, IL-4 can limit inflammatory damage, support resolution, and facilitate tubular repair, in part through effects on macrophage phenotype. However, when IL-4 signaling persists during chronic injury, it may contribute to maladaptive remodeling, including activation of profibrotic myeloid and stromal programs and accumulation of extracellular matrix (ECM), thereby promoting renal fibrosis. This review summarizes evidence on IL-4\u2019s biological properties, its canonical (Janus kinase [JAK]\u2013signal transducer and activator of transcription 6 [STAT6]) and non-canonical (insulin receptor substrate [IRS]\u2013phosphoinositide 3-kinase [PI3K]\u2013protein kinase B [AKT]) signaling pathways, and its roles in renal diseases (including AKI, lupus nephritis, diabetic nephropathy, and other chronic glomerulopathies). We also evaluate the therapeutic rationale for targeting IL-4 signaling and highlight candidate molecular targets to mitigate renal fibrosis. Clarifying these determinants may help identify when and how IL-4\u2013related pathways could be modulated to improve repair while limiting fibrosis.<\/jats:p>","DOI":"10.1186\/s12882-026-04879-0","type":"journal-article","created":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T11:15:59Z","timestamp":1772709359000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The role of interleukin-4 in acute kidney injury and chronic kidney disease: a literature review"],"prefix":"10.1186","volume":"27","author":[{"given":"Mengke","family":"Geng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqian","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keke","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,5]]},"reference":[{"key":"4879_CR1","doi-asserted-by":"crossref","unstructured":"Turgut F, Awad AS, Abdel-Rahman EM. Acute kidney injury: medical causes and pathogenesis. J Clin Med. 2023;12(1).","DOI":"10.3390\/jcm12010375"},{"key":"4879_CR2","doi-asserted-by":"crossref","unstructured":"Niculae A, et al. Pathway from acute kidney injury to chronic kidney disease: molecules involved in renal fibrosis. Int J Mol Sci. 2023;24(18).","DOI":"10.3390\/ijms241814019"},{"issue":"5","key":"4879_CR3","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1038\/nrneph.2015.3","volume":"11","author":"DA Ferenbach","year":"2015","unstructured":"Ferenbach DA, Bonventre JV. Mechanisms of maladaptive repair after AKI leading to accelerated kidney ageing and CKD. Nat Rev Nephrol. 2015;11(5):264\u201376.","journal-title":"Nat Rev Nephrol"},{"issue":"6","key":"4879_CR4","doi-asserted-by":"publisher","first-page":"414","DOI":"10.2471\/BLT.17.206441","volume":"96","author":"VA Luyckx","year":"2018","unstructured":"Luyckx VA, Tonelli M, Stanifer JW. The global burden of kidney disease and the sustainable development goals. Bull World Health Organ. 2018;96(6):414\u2013d422.","journal-title":"Bull World Health Organ"},{"key":"4879_CR5","doi-asserted-by":"publisher","first-page":"108917","DOI":"10.1016\/j.intimp.2022.108917","volume":"108","author":"W Wei","year":"2022","unstructured":"Wei W, et al. The role of IL-10 in kidney disease. Int Immunopharmacol. 2022;108:108917.","journal-title":"Int Immunopharmacol"},{"key":"4879_CR6","doi-asserted-by":"crossref","unstructured":"Iwaszko M, Bia\u0142y S, Bogunia-Kubik K. Significance of interleukin (IL)-4 and IL-13 in inflammatory arthritis. Cells. 2021;10(11).","DOI":"10.3390\/cells10113000"},{"issue":"2","key":"4879_CR7","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1016\/j.kint.2016.08.020","volume":"91","author":"MZ Zhang","year":"2017","unstructured":"Zhang MZ, et al. IL-4\/IL-13-mediated polarization of renal macrophages\/dendritic cells to an M2a phenotype is essential for recovery from acute kidney injury. Kidney Int. 2017;91(2):375\u201386.","journal-title":"Kidney Int"},{"key":"4879_CR8","doi-asserted-by":"publisher","first-page":"107907","DOI":"10.1016\/j.intimp.2021.107907","volume":"98","author":"B Liu","year":"2021","unstructured":"Liu B, et al. Natural killer T cell\/IL-4 signaling promotes bone marrow-derived fibroblast activation and M2 macrophage-to-myofibroblast transition in renal fibrosis. Int Immunopharmacol. 2021;98:107907.","journal-title":"Int Immunopharmacol"},{"key":"4879_CR9","doi-asserted-by":"publisher","first-page":"888","DOI":"10.3389\/fimmu.2018.00888","volume":"9","author":"IS Junttila","year":"2018","unstructured":"Junttila IS. Tuning the cytokine responses: an update on Interleukin (IL)-4 and IL-13 receptor complexes. Front Immunol. 2018;9:888.","journal-title":"Front Immunol"},{"key":"4879_CR10","doi-asserted-by":"crossref","unstructured":"Shi J, et al. Involvement of IL-4, IL-13 and their receptors in pancreatic cancer. Int J Mol Sci. 2021;22(6).","DOI":"10.3390\/ijms22062998"},{"key":"4879_CR11","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pep.2014.01.005","volume":"96","author":"R Li","year":"2014","unstructured":"Li R, et al. Expression of recombinant human IL-4 in Pichia pastoris and relationship between its glycosylation and biological activity. Protein Expr Purif. 2014;96:1\u20137.","journal-title":"Protein Expr Purif"},{"issue":"1","key":"4879_CR12","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1111\/imr.13230","volume":"320","author":"ZJ Bernstein","year":"2023","unstructured":"Bernstein ZJ, et al. Engineering the IL-4\/IL-13 axis for targeted immune modulation. Immunol Rev. 2023;320(1):29\u201357.","journal-title":"Immunol Rev"},{"issue":"8","key":"4879_CR13","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1080\/1744666X.2021.1940962","volume":"17","author":"C Dubin","year":"2021","unstructured":"Dubin C, Duca ED, Guttman-Yassky E. The IL-4, IL-13 and IL-31 pathways in atopic dermatitis. Expert Rev Clin Immunol. 2021;17(8):835\u201352.","journal-title":"Expert Rev Clin Immunol"},{"key":"4879_CR14","doi-asserted-by":"publisher","first-page":"e13444","DOI":"10.7717\/peerj.13444","volume":"10","author":"SM Nur Husna","year":"2022","unstructured":"Nur Husna SM, et al. IL-4\/IL-13 axis as therapeutic targets in allergic rhinitis and asthma. PeerJ. 2022;10:e13444.","journal-title":"PeerJ"},{"key":"4879_CR15","doi-asserted-by":"publisher","first-page":"114730","DOI":"10.1016\/j.biopha.2023.114730","volume":"162","author":"DH Jung","year":"2023","unstructured":"Jung DH, et al. Therapeutic effects of Pulsatilla koreana Nakai extract on ovalbumin-induced allergic rhinitis by inhibition of Th2 cell activation and differentiation via the IL-4\/STAT6\/GATA3 pathway. Biomed Pharmacother. 2023;162:114730.","journal-title":"Biomed Pharmacother"},{"issue":"5","key":"4879_CR16","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1007\/s00281-016-0568-y","volume":"38","author":"Y Yamanishi","year":"2016","unstructured":"Yamanishi Y, Karasuyama H. Basophil-derived IL-4 plays versatile roles in immunity. Semin Immunopathol. 2016;38(5):615\u201322.","journal-title":"Semin Immunopathol"},{"issue":"1","key":"4879_CR17","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1189\/jlb.0108058","volume":"85","author":"LA Spencer","year":"2009","unstructured":"Spencer LA, et al. Human eosinophils constitutively express multiple Th1, Th2, and immunoregulatory cytokines that are secreted rapidly and differentially. J Leukoc Biol. 2009;85(1):117\u201323.","journal-title":"J Leukoc Biol"},{"key":"4879_CR18","doi-asserted-by":"publisher","first-page":"w13999","DOI":"10.4414\/smw.2014.13999","volume":"144","author":"T H\u00fcgle","year":"2014","unstructured":"H\u00fcgle T. Beyond allergy: the role of mast cells in fibrosis. Swiss Med Wkly. 2014;144:w13999.","journal-title":"Swiss Med Wkly"},{"key":"4879_CR19","doi-asserted-by":"crossref","unstructured":"Furue M. Regulation of filaggrin, loricrin, and involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: pathogenic implications in atopic dermatitis. Int J Mol Sci. 2020;21(15).","DOI":"10.3390\/ijms21155382"},{"issue":"16","key":"4879_CR20","doi-asserted-by":"publisher","first-page":"5275","DOI":"10.7150\/ijbs.86701","volume":"19","author":"CY Ko","year":"2023","unstructured":"Ko CY, et al. Omentin-1 ameliorates the progress of osteoarthritis by promoting IL-4-dependent anti-inflammatory responses and M2 macrophage polarization. Int J Biol Sci. 2023;19(16):5275\u201389.","journal-title":"Int J Biol Sci"},{"key":"4879_CR21","doi-asserted-by":"publisher","first-page":"172","DOI":"10.3389\/fphys.2020.00172","volume":"11","author":"DB Peruchetti","year":"2020","unstructured":"Peruchetti DB, et al. IL-4 receptor \u03b1 chain protects the kidney against tubule-interstitial injury induced by albumin overload. Front Physiol. 2020;11:172.","journal-title":"Front Physiol"},{"key":"4879_CR22","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1146\/annurev-immunol-101921-041206","volume":"41","author":"JE Allen","year":"2023","unstructured":"Allen JE. IL-4 and IL-13: regulators and effectors of wound repair. Annu Rev Immunol. 2023;41:229\u201354.","journal-title":"Annu Rev Immunol"},{"issue":"2","key":"4879_CR23","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1007\/s00403-019-01972-3","volume":"312","author":"JK Nguyen","year":"2020","unstructured":"Nguyen JK, et al. The IL-4\/IL-13 axis in skin fibrosis and scarring: mechanistic concepts and therapeutic targets. Arch Dermatol Res. 2020;312(2):81\u201392.","journal-title":"Arch Dermatol Res"},{"key":"4879_CR24","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.fsi.2021.11.007","volume":"120","author":"X Yuan","year":"2022","unstructured":"Yuan X, et al. Molecular characterization, expression analysis and cellular location of IL-4\/13 receptors in large yellow croaker (Larimichthys crocea). Fish Shellfish Immunol. 2022;120:45\u201355.","journal-title":"Fish Shellfish Immunol"},{"key":"4879_CR25","doi-asserted-by":"crossref","unstructured":"Liu J, Wang F, Luo F. The role of JAK\/STAT pathway in fibrotic diseases: molecular and cellular mechanisms. Biomolecules. 2023;13(1).","DOI":"10.3390\/biom13010119"},{"issue":"1","key":"4879_CR26","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/cea.13491","volume":"50","author":"H Harb","year":"2020","unstructured":"Harb H, Chatila TA. Mechanisms dupilumab. Clin Exp Allergy. 2020;50(1):5\u201314.","journal-title":"Mechanisms Dupilumab Clin Exp Allergy"},{"issue":"4","key":"4879_CR27","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.immuni.2016.09.016","volume":"45","author":"SC Huang","year":"2016","unstructured":"Huang SC, et al. Metabolic reprogramming mediated by the mTORC2-IRF4 signaling axis is essential for macrophage alternative activation. Immunity. 2016;45(4):817\u201330.","journal-title":"Immunity"},{"issue":"3","key":"4879_CR28","doi-asserted-by":"publisher","first-page":"110719","DOI":"10.1016\/j.celrep.2022.110719","volume":"39","author":"M-C Lee","year":"2022","unstructured":"Lee M-C. Type I interferon antagonism of the JMJD3-IRF4 pathway modulates macrophage activation and polarization. Cell Rep. 2022;39(3):110719.","journal-title":"Cell Rep"},{"issue":"5","key":"4879_CR29","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1016\/j.jaci.2010.01.054","volume":"125","author":"R Tachdjian","year":"2010","unstructured":"Tachdjian R, et al. In vivo regulation of the allergic response by the IL-4 receptor alpha chain immunoreceptor tyrosine-based inhibitory motif. J Allergy Clin Immunol. 2010;125(5):1128\u2013e11368.","journal-title":"J Allergy Clin Immunol"},{"issue":"12","key":"4879_CR30","doi-asserted-by":"publisher","first-page":"1838","DOI":"10.2215\/CJN.15611219","volume":"15","author":"KD Liu","year":"2020","unstructured":"Liu KD, et al. AKI!now initiative: recommendations for awareness, recognition, and management of AKI. Clin J Am Soc Nephrol. 2020;15(12):1838\u201347.","journal-title":"Clin J Am Soc Nephrol"},{"issue":"3","key":"4879_CR31","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1016\/j.semnephrol.2019.02.009","volume":"39","author":"GT Obrador","year":"2019","unstructured":"Obrador GT, Levin A. CKD hotspots: challenges and areas of opportunity. Semin Nephrol. 2019;39(3):308\u201314.","journal-title":"Semin Nephrol"},{"issue":"6","key":"4879_CR32","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1016\/j.kint.2017.12.016","volume":"93","author":"J Barrera-Chimal","year":"2018","unstructured":"Barrera-Chimal J, et al. The myeloid mineralocorticoid receptor controls inflammatory and fibrotic responses after renal injury via macrophage interleukin-4 receptor signaling. Kidney Int. 2018;93(6):1344\u201355.","journal-title":"Kidney Int"},{"issue":"6","key":"4879_CR33","doi-asserted-by":"publisher","first-page":"3314","DOI":"10.1111\/jcmm.15005","volume":"24","author":"R Mao","year":"2020","unstructured":"Mao R, et al. Peritoneal M2 macrophage transplantation as a potential cell therapy for enhancing renal repair in acute kidney injury. J Cell Mol Med. 2020;24(6):3314\u201327.","journal-title":"J Cell Mol Med"},{"issue":"23","key":"4879_CR34","doi-asserted-by":"publisher","first-page":"e70216","DOI":"10.1096\/fj.202402318R","volume":"38","author":"H Zhou","year":"2024","unstructured":"Zhou H, et al. CD11b deficiency attenuates the ischemia\/reperfusion-induced AKI-to-CKD process by regulating macrophage polarization. Faseb j. 2024;38(23):e70216.","journal-title":"Faseb j"},{"issue":"6","key":"4879_CR35","doi-asserted-by":"publisher","first-page":"1433","DOI":"10.1016\/j.kint.2017.04.021","volume":"92","author":"H Liang","year":"2017","unstructured":"Liang H, et al. The IL-4 receptor \u03b1 has a critical role in bone marrow-derived fibroblast activation and renal fibrosis. Kidney Int. 2017;92(6):1433\u201343.","journal-title":"Kidney Int"},{"key":"4879_CR36","doi-asserted-by":"crossref","unstructured":"Jiao B, et al. STAT6 deficiency attenuates myeloid fibroblast activation and macrophage polarization in experimental folic acid nephropathy. Cells. 2021;10(11).","DOI":"10.3390\/cells10113057"},{"key":"4879_CR37","doi-asserted-by":"publisher","first-page":"108142","DOI":"10.1016\/j.intimp.2021.108142","volume":"100","author":"M Chen","year":"2021","unstructured":"Chen M, et al. IRF-4 deficiency reduces inflammation and kidney fibrosis after folic acid-induced acute kidney injury. Int Immunopharmacol. 2021;100:108142.","journal-title":"Int Immunopharmacol"},{"key":"4879_CR38","doi-asserted-by":"publisher","first-page":"978262","DOI":"10.3389\/fimmu.2022.978262","volume":"13","author":"H Liang","year":"2022","unstructured":"Liang H, et al. Jmjd3\/IRF4 axis aggravates myeloid fibroblast activation and m2 macrophage to myofibroblast transition in renal fibrosis. Front Immunol. 2022;13:978262.","journal-title":"Front Immunol"},{"issue":"1","key":"4879_CR39","doi-asserted-by":"publisher","first-page":"2327498","DOI":"10.1080\/0886022X.2024.2327498","volume":"46","author":"Y Zhou","year":"2024","unstructured":"Zhou Y, et al. Iguratimod prevents renal fibrosis in unilateral ureteral obstruction model mice by suppressing M2 macrophage infiltration and macrophage-myofibroblast transition. Ren Fail. 2024;46(1):2327498.","journal-title":"Ren Fail"},{"key":"4879_CR40","doi-asserted-by":"publisher","first-page":"107623","DOI":"10.1016\/j.phrs.2025.107623","volume":"213","author":"Y Chen","year":"2025","unstructured":"Chen Y, et al. Inhibition of Kv1.3 channel restrains macrophage M2 polarization and ameliorates renal fibrosis via regulating STAT6 phosphorylation. Pharmacol Res. 2025;213:107623.","journal-title":"Pharmacol Res"},{"key":"4879_CR41","doi-asserted-by":"publisher","first-page":"123564","DOI":"10.1016\/j.lfs.2025.123564","volume":"370","author":"W Liang","year":"2025","unstructured":"Liang W, et al. LKB1 activated by NaB inhibits the IL-4\/STAT6 axis and ameliorates renal fibrosis through the suppression of M2 macrophage polarization. Life Sci. 2025;370:123564.","journal-title":"Life Sci"},{"key":"4879_CR42","doi-asserted-by":"publisher","first-page":"683249","DOI":"10.3389\/fimmu.2021.683249","volume":"12","author":"CL Liang","year":"2021","unstructured":"Liang CL, et al. Total glucosides of paeony ameliorate pristane-induced lupus nephritis by inducing PD-1 ligands(+) macrophages via activating IL-4\/STAT6\/PD-L2 signaling. Front Immunol. 2021;12:683249.","journal-title":"Front Immunol"},{"issue":"1","key":"4879_CR43","doi-asserted-by":"publisher","first-page":"3389","DOI":"10.1038\/s41467-024-47691-w","volume":"15","author":"J Tchen","year":"2024","unstructured":"Tchen J, et al. PD-L1- and IL-4-expressing basophils promote pathogenic accumulation of T follicular helper cells in lupus. Nat Commun. 2024;15(1):3389.","journal-title":"Nat Commun"},{"issue":"2","key":"4879_CR44","doi-asserted-by":"publisher","first-page":"2378210","DOI":"10.1080\/0886022X.2024.2378210","volume":"46","author":"Y Gu","year":"2024","unstructured":"Gu Y, et al. M2 macrophage infusion ameliorates diabetic glomerulopathy via the JAK2\/STAT3 pathway in db\/db mice. Ren Fail. 2024;46(2):2378210.","journal-title":"Ren Fail"},{"key":"4879_CR45","doi-asserted-by":"crossref","unstructured":"Kim AH, et al. B cell-derived IL-4 acts on podocytes to induce proteinuria and foot process effacement. JCI Insight. 2017;2(21).","DOI":"10.1172\/jci.insight.81836"},{"key":"4879_CR46","doi-asserted-by":"publisher","first-page":"p9086758","DOI":"10.1155\/2019\/9086758","volume":"2019","author":"PAM Cavalcante","year":"2019","unstructured":"Cavalcante PAM, et al. Nephropathy in hypertensive animals is linked to M2 macrophages and increased expression of the YM1\/Chi3l3 protein. Mediators Inflamm. 2019;2019:p9086758.","journal-title":"Mediators Inflamm"},{"issue":"6","key":"4879_CR47","doi-asserted-by":"publisher","first-page":"4743","DOI":"10.3233\/THC-241175","volume":"32","author":"C Yao","year":"2024","unstructured":"Yao C, et al. Cyclophosphamide ameliorates membranous nephropathy by upregulating miR-223 expression, promoting M2 macrophage polarization and inhibiting inflammation. Technol Health Care. 2024;32(6):4743\u201356.","journal-title":"Technol Health Care"},{"issue":"6","key":"4879_CR48","doi-asserted-by":"publisher","first-page":"F1105","DOI":"10.1152\/ajprenal.00285.2020","volume":"319","author":"M Jiang","year":"2020","unstructured":"Jiang M, et al. Mitochondrial dysfunction and the AKI-to-CKD transition. Am J Physiol Ren Physiol. 2020;319(6):F1105\u201316.","journal-title":"Am J Physiol Ren Physiol"},{"key":"4879_CR49","doi-asserted-by":"crossref","unstructured":"Wang Z, Zhang C. From AKI to CKD: maladaptive repair and the underlying mechanisms. Int J Mol Sci. 2022;23(18).","DOI":"10.3390\/ijms231810880"},{"key":"4879_CR50","doi-asserted-by":"publisher","first-page":"108240","DOI":"10.1016\/j.pharmthera.2022.108240","volume":"237","author":"Y Fu","year":"2022","unstructured":"Fu Y, et al. Inflammation in kidney repair: mechanism and therapeutic potential. Pharmacol Ther. 2022;237:108240.","journal-title":"Pharmacol Ther"},{"key":"4879_CR51","doi-asserted-by":"crossref","unstructured":"N\u00f8rg\u00e5rd M, Svenningsen P. Acute kidney injury by ischemia\/reperfusion and extracellular vesicles. Int J Mol Sci. 2023;24(20).","DOI":"10.3390\/ijms242015312"},{"issue":"2","key":"4879_CR52","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.ccc.2020.11.009","volume":"37","author":"C Massoth","year":"2021","unstructured":"Massoth C, Zarbock A, Meersch M. Acute kidney injury in cardiac surgery. Crit Care Clin. 2021;37(2):267\u201378.","journal-title":"Crit Care Clin"},{"issue":"6","key":"4879_CR53","first-page":"550","volume":"25","author":"MA Perazella","year":"2019","unstructured":"Perazella MA. Drug-induced acute kidney injury: diverse mechanisms of tubular injury. Curr Opin Crit Care. 2019;25(6):550\u20137.","journal-title":"Curr Opin Crit Care"},{"issue":"8","key":"4879_CR54","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.2215\/CJN.11290821","volume":"17","author":"MA Perazella","year":"2022","unstructured":"Perazella MA, Rosner MH. Drug-induced acute kidney injury. Clin J Am Soc Nephrol. 2022;17(8):1220\u201333.","journal-title":"Clin J Am Soc Nephrol"},{"issue":"7","key":"4879_CR55","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1681\/ASN.2010070693","volume":"22","author":"Q Cao","year":"2011","unstructured":"Cao Q, et al. IL-25 induces M2 macrophages and reduces renal injury in proteinuric kidney disease. J Am Soc Nephrol. 2011;22(7):1229\u201339.","journal-title":"J Am Soc Nephrol"},{"issue":"4","key":"4879_CR56","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1002\/ame2.12194","volume":"4","author":"LJ Yan","year":"2021","unstructured":"Yan LJ. Folic acid-induced animal model of kidney disease. Anim Model Exp Med. 2021;4(4):329\u201342.","journal-title":"Anim Model Exp Med"},{"issue":"4","key":"4879_CR57","doi-asserted-by":"publisher","first-page":"2827","DOI":"10.1152\/physrev.00027.2022","volume":"103","author":"R N\u00f8rregaard","year":"2023","unstructured":"N\u00f8rregaard R, et al. Obstructive nephropathy and molecular pathophysiology of renal interstitial fibrosis. Physiol Rev. 2023;103(4):2827\u201372.","journal-title":"Physiol Rev"},{"issue":"Suppl 1","key":"4879_CR58","doi-asserted-by":"publisher","first-page":"s03","DOI":"10.1590\/1806-9282.66.s1.3","volume":"66Suppl 1","author":"AL Ammirati","year":"2020","unstructured":"Ammirati AL. Chronic kidney disease. Rev Assoc Med Bras (1992). 2020;66Suppl 1(Suppl 1):s03\u20139.","journal-title":"Rev Assoc Med Bras (1992)"},{"issue":"4","key":"4879_CR59","first-page":"302","volume":"4","author":"M Kazemi Arababadi","year":"2010","unstructured":"Kazemi Arababadi M. Interleukin-4 gene polymorphisms in type 2 diabetic patients with nephropathy. Iran J Kidney Dis. 2010;4(4):302\u20136.","journal-title":"Iran J Kidney Dis"},{"key":"4879_CR60","doi-asserted-by":"publisher","first-page":"79","DOI":"10.3389\/fgene.2020.00079","volume":"11","author":"M Mai","year":"2020","unstructured":"Mai M, et al. Association of TGF-\u03b21, IL-4, and IL-10 polymorphisms with chronic kidney disease susceptibility: a meta-analysis. Front Genet. 2020;11:79.","journal-title":"Front Genet"},{"key":"4879_CR61","doi-asserted-by":"publisher","first-page":"102871","DOI":"10.1016\/j.jaut.2022.102871","volume":"132","author":"C Yu","year":"2022","unstructured":"Yu C, et al. Lupus nephritis: new progress in diagnosis and treatment. J Autoimmun. 2022;132:102871.","journal-title":"J Autoimmun"},{"key":"4879_CR62","doi-asserted-by":"crossref","unstructured":"Obri\u0219c\u0103 B, et al. Advances in lupus nephritis pathogenesis: from bench to bedside. Int J Mol Sci. 2021;22(7).","DOI":"10.3390\/ijms22073766"},{"issue":"10","key":"4879_CR63","first-page":"e30330","volume":"14","author":"MA Ameer","year":"2022","unstructured":"Ameer MA, et al. An Overview of systemic lupus erythematosus (SLE) pathogenesis, classification, and management. Cureus. 2022;14(10):e30330.","journal-title":"Cureus"},{"key":"4879_CR64","doi-asserted-by":"crossref","unstructured":"Peng Y, et al. Regulatory mechanism of M1\/M2 macrophage polarization in the development of autoimmune diseases. Mediators Inflamm. 2023;2023:8821610.","DOI":"10.1155\/2023\/8821610"},{"key":"4879_CR65","doi-asserted-by":"publisher","first-page":"866549","DOI":"10.3389\/fimmu.2022.866549","volume":"13","author":"H Ko","year":"2022","unstructured":"Ko H, Kim CJ, Im SH. Helper 2-associated immunity in the pathogenesis of systemic lupus erythematosus. Front Immunol. 2022;13:866549.","journal-title":"Front Immunol"},{"issue":"6","key":"4879_CR66","doi-asserted-by":"publisher","first-page":"147916412110588","DOI":"10.1177\/14791641211058856","volume":"18","author":"S Thipsawat","year":"2021","unstructured":"Thipsawat S. Early detection of diabetic nephropathy in patient with type 2 diabetes mellitus: A review of the literature. Diab Vasc Dis Res. 2021;18(6):14791641211058856.","journal-title":"Diab Vasc Dis Res"},{"key":"4879_CR67","doi-asserted-by":"publisher","first-page":"746151","DOI":"10.3389\/fimmu.2021.746151","volume":"12","author":"S Russo","year":"2021","unstructured":"Russo S, et al. Meta-inflammation and metabolic reprogramming of macrophages in diabetes and obesity: The Importance of Metabolites. Front Immunol. 2021;12:746151.","journal-title":"Front Immunol"},{"key":"4879_CR68","doi-asserted-by":"publisher","first-page":"p1497449","DOI":"10.1155\/2021\/1497449","volume":"2021","author":"N Samsu","year":"2021","unstructured":"Samsu N. Diabetic nephropathy: challenges in pathogenesis, diagnosis, and treatment. Biomed Res Int. 2021;2021:p1497449.","journal-title":"Biomed Res Int"},{"issue":"2","key":"4879_CR69","first-page":"2778","volume":"17","author":"Z Zhang","year":"2018","unstructured":"Zhang Z, et al. Increased soluble ST2 and IL\u20134 serum levels are associated with disease severity in patients with membranous nephropathy. Mol Med Rep. 2018;17(2):2778\u201386.","journal-title":"Mol Med Rep"},{"issue":"7","key":"4879_CR70","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1093\/ckj\/sfaa265","volume":"14","author":"N Roca","year":"2021","unstructured":"Roca N, et al. Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes. Clin Kidney J. 2021;14(7):1826\u201334.","journal-title":"Clin Kidney J"},{"issue":"4","key":"4879_CR71","first-page":"4103","volume":"18","author":"Y Tang","year":"2018","unstructured":"Tang Y, et al. Corticosteroid therapy in IgA nephropathy with minimal proteinuria and high renal pathological score: A single\u2013center cohort study. Mol Med Rep. 2018;18(4):4103\u201312.","journal-title":"Mol Med Rep"},{"key":"4879_CR72","doi-asserted-by":"publisher","first-page":"27659","DOI":"10.1038\/srep27659","volume":"6","author":"H Huang","year":"2016","unstructured":"Huang H, et al. CD4(+)CD25(+) T Cells in primary malignant hypertension related kidney injury. Sci Rep. 2016;6:27659.","journal-title":"Sci Rep"},{"issue":"3","key":"4879_CR73","doi-asserted-by":"publisher","first-page":"187","DOI":"10.15171\/jnp.2017.32","volume":"6","author":"M Stangou","year":"2017","unstructured":"Stangou M, et al. Impact of \u03a4h1 and \u03a4h2 cytokines in the progression of idiopathic nephrotic syndrome due to focal segmental glomerulosclerosis and minimal change disease. J Nephropathol. 2017;6(3):187\u201395.","journal-title":"J Nephropathol"},{"key":"4879_CR74","doi-asserted-by":"publisher","first-page":"681748","DOI":"10.3389\/fimmu.2021.681748","volume":"12","author":"Y Wen","year":"2021","unstructured":"Wen Y, et al. Macrophage heterogeneity in kidney injury and fibrosis. Front Immunol. 2021;12:681748.","journal-title":"Front Immunol"},{"key":"4879_CR75","doi-asserted-by":"crossref","unstructured":"Bell RMB, Denby L. Myeloid heterogeneity in kidney disease as revealed through single-cell RNA sequencing. Kidney 360. 2021;2(11):1844\u201351.","DOI":"10.34067\/KID.0003682021"},{"issue":"12","key":"4879_CR76","doi-asserted-by":"publisher","first-page":"2833","DOI":"10.1681\/ASN.2020060806","volume":"31","author":"BR Conway","year":"2020","unstructured":"Conway BR, et al. Kidney single-cell atlas reveals myeloid heterogeneity in progression and regression of kidney disease. J Am Soc Nephrol. 2020;31(12):2833\u201354.","journal-title":"J Am Soc Nephrol"},{"issue":"38","key":"4879_CR77","doi-asserted-by":"publisher","first-page":"e2309752","DOI":"10.1002\/advs.202309752","volume":"11","author":"YL Zhang","year":"2024","unstructured":"Zhang YL, et al. Identification of a novel ECM remodeling macrophage subset in AKI to CKD transition by integrative spatial and single-cell analysis. Adv Sci (Weinh). 2024;11(38):e2309752.","journal-title":"Adv Sci (Weinh)"},{"issue":"8","key":"4879_CR78","doi-asserted-by":"publisher","first-page":"e13899","DOI":"10.1111\/cts.13899","volume":"17","author":"MR McCann","year":"2024","unstructured":"McCann MR, et al. Dupilumab: Mechanism of action, clinical, and translational science. Clin Transl Sci. 2024;17(8):e13899.","journal-title":"Clin Transl Sci"},{"issue":"12","key":"4879_CR79","doi-asserted-by":"publisher","first-page":"3060","DOI":"10.1681\/ASN.2014070717","volume":"26","author":"J Yan","year":"2015","unstructured":"Yan J, et al. JAK3\/STAT6 stimulates bone marrow-derived fibroblast activation in renal fibrosis. J Am Soc Nephrol. 2015;26(12):3060\u201371.","journal-title":"J Am Soc Nephrol"},{"issue":"4","key":"4879_CR80","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s40265-023-01840-5","volume":"83","author":"P N\u00fa\u00f1ez","year":"2023","unstructured":"N\u00fa\u00f1ez P, Quera R, Yarur AJ. Safety of janus kinase inhibitors in inflammatory bowel diseases. Drugs. 2023;83(4):299\u2013314.","journal-title":"Drugs"},{"key":"4879_CR81","doi-asserted-by":"publisher","first-page":"735014","DOI":"10.3389\/fimmu.2021.735014","volume":"12","author":"B Jiao","year":"2021","unstructured":"Jiao B, et al. Pharmacological inhibition of STAT6 ameliorates myeloid fibroblast activation and alternative macrophage polarization in renal fibrosis. Front Immunol. 2021;12:735014.","journal-title":"Front Immunol"},{"issue":"9","key":"4879_CR82","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/s41573-021-00199-0","volume":"20","author":"MJ Henley","year":"2021","unstructured":"Henley MJ, Koehler AN. Advances in targeting \u2018undruggable\u2019 transcription factors with small molecules. Nat Rev Drug Discov. 2021;20(9):669\u201388.","journal-title":"Nat Rev Drug Discov"},{"issue":"17","key":"4879_CR83","doi-asserted-by":"publisher","first-page":"2250","DOI":"10.1111\/bph.16096","volume":"180","author":"C An","year":"2023","unstructured":"An C, et al. Jumonji domain-containing protein-3 (JMJD3) promotes myeloid fibroblast activation and macrophage polarization in kidney fibrosis. Br J Pharmacol. 2023;180(17):2250\u201365.","journal-title":"Br J Pharmacol"},{"issue":"7411","key":"4879_CR84","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1038\/nature11262","volume":"488","author":"L Kruidenier","year":"2012","unstructured":"Kruidenier L, et al. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature. 2012;488(7411):404\u20138.","journal-title":"Nature"},{"issue":"7520","key":"4879_CR85","doi-asserted-by":"publisher","first-page":"E1","DOI":"10.1038\/nature13688","volume":"514","author":"B Heinemann","year":"2014","unstructured":"Heinemann B, et al. Inhibition of demethylases by GSK-J1\/J4. Nature. 2014;514(7520):E1\u20132.","journal-title":"Nature"},{"key":"4879_CR86","doi-asserted-by":"publisher","first-page":"123338","DOI":"10.1016\/j.lfs.2024.123338","volume":"362","author":"Z Dragan","year":"2025","unstructured":"Dragan Z, Pollock CA, Huang C. Insight into a multifunctional potassium channel Kv1.3 and its novel implication in chronic kidney disease. Life Sci. 2025;362:123338.","journal-title":"Life Sci"},{"key":"4879_CR87","doi-asserted-by":"publisher","first-page":"116651","DOI":"10.1016\/j.biopha.2024.116651","volume":"175","author":"S Cheng","year":"2024","unstructured":"Cheng S, et al. Voltage-gated potassium channel 1.3: A promising molecular target in multiple disease therapy. Biomed Pharmacother. 2024;175:116651.","journal-title":"Biomed Pharmacother"},{"key":"4879_CR88","doi-asserted-by":"publisher","first-page":"277","DOI":"10.3389\/fimmu.2019.00277","volume":"10","author":"D Parada Venegas","year":"2019","unstructured":"Parada Venegas D, et al. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol. 2019;10:277.","journal-title":"Front Immunol"}],"container-title":["BMC Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12882-026-04879-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12882-026-04879-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12882-026-04879-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T19:25:30Z","timestamp":1781637930000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12882-026-04879-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,5]]},"references-count":88,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4879"],"URL":"https:\/\/doi.org\/10.1186\/s12882-026-04879-0","relation":{},"ISSN":["1471-2369"],"issn-type":[{"value":"1471-2369","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,5]]},"assertion":[{"value":"14 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable, as this study is a literature review and did not involve human participants or animals.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"233"}}