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Its burden continues to increase despite advances in glycemic and blood pressure control. This persistent risk highlights the need for therapeutic strategies that address injury-amplifying mechanisms beyond conventional metabolic and hemodynamic pathways. Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, has emerged as a contributor to renal injury in DKD. However, its precise role in human disease is incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Recent Advances:<\/jats:title>\n                    <jats:p>Ferroptosis is closely linked to lipid peroxidation-derived danger signals that promote innate immune activation, including M1 macrophage polarization, neutrophil infiltration, dendritic-cell maturation, TLR4 signaling, and NLRP3 inflammasome activation. Ferroptotic cells release damage-associated molecular patterns, including HMGB1, which activate inflammatory cascades. In turn, inflammatory cytokines disrupt iron homeostasis, increase oxidative stress, and further sensitize renal cells to ferroptosis, forming a self-amplifying ferroptosis\u2013immunity feedback loop.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Critical Issues:<\/jats:title>\n                    <jats:p>Candidate biomarkers, including GPX4 depletion, ACSL4 expression, lipid peroxidation products, interleukin-18, and NLRP3 activation, may support earlier risk assessment and patient stratification. However, clinical validation is limited, and standardized biomarker thresholds, longitudinal human data, renal-cell-specific targeting, and long-term safety data are still lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Future Directions:<\/jats:title>\n                    <jats:p>\n                      Therapeutic strategies under investigation include ferroptosis inhibitors, iron chelators, GPX4-directed approaches, TLR4\/NLRP3-targeted immunomodulators, kidney-targeted nanoparticles, and CRISPR-based modulation of ferroptosis regulators. Multiomics profiling and artificial intelligence may further support rational combination therapies. Targeting the ferroptosis\u2013immunity axis alongside optimal glycemic control may provide a complementary mechanism-based strategy to delay DKD progression.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      00, 000\u2013000.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864261483982","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T02:42:53Z","timestamp":1788403373000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["The Ferroptosis\u2013Immunity Axis in Diabetic Kidney Disease: Emerging Therapeutic Targets"],"prefix":"10.1177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9549-7552","authenticated-orcid":false,"given":"Wen","family":"Zhang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumei","family":"Xu","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhijian","family":"Cao","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First People\u2019s Hospital of Hangzhou Lin\u2019an District, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhili","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Hematology and Rheumatology, Tianchang People\u2019s Hospital, Chuzhou, Anhui, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihua","family":"Deng","sequence":"additional","affiliation":[{"name":"Jiangshan Hospital of Traditional Chinese Medicine, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuju","family":"Zhou","sequence":"additional","affiliation":[{"name":"Jiangshan Hospital of Traditional Chinese Medicine, Zhejiang, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1469-1722","authenticated-orcid":false,"given":"Xiaoran","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The First People\u2019s Hospital of Hangzhou Lin\u2019an District, Hangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26146996"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e22783"},{"issue":"22","key":"e_1_3_3_4_1","first-page":"10101","article-title":"Effects of IL-1\u03b2 and IL-18 induced by NLRP3 inflammasome activation on myocardial reperfusion injury after PCI","volume":"23","author":"Bai YJ","year":"2019","unstructured":"Bai YJ, , Li ZG, , Liu WH, et al. 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