{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T09:34:58Z","timestamp":1789810498207,"version":"4.0.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"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. Endocrinol."],"abstract":"\n Objective<\/jats:title>\n Prolactin (PRL) is increasingly recognized as a pleiotropic hormone with potent immunoregulatory properties; however, its involvement in systemic inflammation among diabetic kidney disease (DKD) patients has not been defined. This study aimed to investigate the potential association between serum PRL levels and micro-inflammation in patients with DKD.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In this cross-sectional investigation, 994 patients with type 2 diabetes mellitus (T2DM)-associated DKD were enrolled. Multivariable linear mixed-effects models were used to quantify the relationship between serum PRL and the systemic immune-inflammation index (SII) and other clinical parameters. Restricted cubic spline (RCS) analyses were fitted to test for non-linearity and stratified and sensitivity analyses were performed to assess robustness.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The median serum PRL level was 344.40 mIU\/L (interquartile range: 258.80\u2013463.10). After multivariable adjustment, serum PRL were positively associated with white blood cell count, neutrophil count, serum ferritin, serum phosphorus and intact parathyroid hormone (iPTH) levels, and inversely associated with serum albumin. For every 100 mIU\/L increase in serum PRL, the SII increased by an average of 7.10 units (95% CI: 3.13 to 11.07;\n p<\/jats:italic>\n = 5.12 \u00d7 10\n -4<\/jats:sup>\n ). Stratified and sensitivity analyses confirmed the robustness of this association. RCS analysis revealed a significant nonlinear relationship between serum PRL and SII (\n p<\/jats:italic>\n for nonlinearity = 0.002), with an inflection point at 282.85 mIU\/L. PRL levels above this inflection point showed a significant positive association with SII, whereas levels below it showed a negative association.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n In patients with DKD, serum PRL exhibits an independent, nonlinear association with SII, characterized by a threshold around 282.85 mIU\/L. This finding suggests that PRL may be linked to the dysregulated immune-inflammation axis in DKD, warranting further mechanistic and longitudinal investigation.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fendo.2026.1772810","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T11:08:26Z","timestamp":1772449706000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Correlation between serum prolactin and the systemic immune-inflammation index in diabetic kidney disease: a cross-sectional study"],"prefix":"10.3389","volume":"17","author":[{"given":"Yinhui","family":"Li","sequence":"first","affiliation":[{"name":"Center for Nephrology and Clinical Metabolomics and Division of Nephrology, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhonghao","family":"Qin","sequence":"additional","affiliation":[{"name":"Center for Nephrology and Clinical Metabolomics and Division of Nephrology, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Si","sequence":"additional","affiliation":[{"name":"Center for Nephrology and Clinical Metabolomics and Division of Nephrology, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shijie","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Nephrology and Clinical Metabolomics and Division of Nephrology, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haichao","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Nephrology and Clinical Metabolomics and Division of Nephrology, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanjie","family":"Yu","sequence":"additional","affiliation":[{"name":"Center for Nephrology and Clinical Metabolomics and Division of Nephrology, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaimin","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Nephrology and Clinical Metabolomics and Division of Nephrology, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine","place":["Shanghai, China"]},{"name":"Department of Laboratory, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Peng","sequence":"additional","affiliation":[{"name":"Center for Nephrology and Clinical Metabolomics and Division of Nephrology, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghao","family":"Kong","sequence":"additional","affiliation":[{"name":"Center for Nephrology and Clinical Metabolomics and Division of Nephrology, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Nephrology and Clinical Metabolomics and Division of Nephrology, Shanghai Tenth People\u2019s Hospital, Tongji University School of Medicine","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-019-0234-4","article-title":"Innate immunity in diabetic kidney disease","volume":"16","author":"Tang","year":"2020","journal-title":"Nat Rev Nephrol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(20)30045-3","article-title":"Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"395","year":"2020","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"20234","DOI":"10.1038\/s41598-023-47091-y","article-title":"Global burden and influencing factors of chronic kidney disease due to type 2 diabetes in adults aged 20\u201359 years, 1990\u20132019","volume":"13","author":"Xie","year":"2023","journal-title":"Sci Rep"},{"key":"B4","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1186\/s12882-025-03953-3","article-title":"New insights in the treatment of DKD: recent advances and future prospects","volume":"26","author":"Zhao","year":"2025","journal-title":"BMC Nephrol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.958790","article-title":"Immune responses in diabetic nephropathy: Pathogenic mechanisms and therapeutic target","volume":"13","author":"Chen","year":"2022","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0415-5","article-title":"A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes","volume":"25","author":"Niewczas","year":"2019","journal-title":"Nat Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2337\/dc25-S011","article-title":"Chronic kidney disease and risk management: standards of care in diabetes\u20142025","volume":"48","author":"ElSayed","year":"2025","journal-title":"Diabetes Care"},{"key":"B8","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41574-025-01171-3","article-title":"Mechanisms of diabetic kidney disease and established and emerging treatments","volume":"22","author":"Martinez Leon","year":"2026","journal-title":"Nat Rev Endocrinol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2025.106676","article-title":"Acute hyperglycemia induces podocyte apoptosis by monocyte TNF-\u03b1 release, a process attenuated by vitamin D and GLP-1 receptor agonists","volume":"247","author":"Zhang","year":"2025","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1186\/s12933-025-02777-7","article-title":"Impact of sodium-glucose transport protein-2 (SGLT2) inhibitors on the inflammasome pathway in acute myocardial infarction in type 2 diabetes mellitus: a comprehensive review","volume":"24","author":"Yoo","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.863640","article-title":"Systemic immune-inflammation index is associated with increased urinary albumin excretion: A population-based study","volume":"13","author":"Qin","year":"2022","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.Ccr-14-0442","article-title":"Systemic immune-inflammation index predicts prognosis of patients after curative resection for hepatocellular carcinoma","volume":"20","author":"Hu","year":"2014","journal-title":"Clin Cancer Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.709553","article-title":"Systemic inflammation index values are associated with worsened disease severity and poor response to autoimmune encephalitis treatment","volume":"12","author":"Mei","year":"2021","journal-title":"Front Neurol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-022-03320-3","article-title":"Could systemic immune inflammation index be a new parameter for diagnosis and disease activity assessment in systemic lupus erythematosus","volume":"55","author":"Ozdemir","year":"2023","journal-title":"Int Urol Nephrol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-020-05266-2","article-title":"Systemic immune-inflammation index combined with ferritin can serve as a reliable assessment score for adult-onset Still\u2019s disease","volume":"40","author":"Kim","year":"2021","journal-title":"Clin Rheumatol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1186\/s12890-023-02583-5","article-title":"Association between systemic immune-inflammation index and chronic obstructive pulmonary disease: a population-based study","volume":"23","author":"Ye","year":"2023","journal-title":"BMC Pulm Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24098414","article-title":"Assessing the relationship between systemic immune-inflammation index and metabolic syndrome in children with obesity","volume":"24","author":"Nicoar\u0103","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1097\/mca.0000000000001037","article-title":"Systemic immune-inflammation index predicts the severity of coronary stenosis in patients with coronary heart disease","volume":"32","author":"Liu","year":"2021","journal-title":"Coron Artery Dis"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.2147\/dmso.S447026","article-title":"Association of systemic immune-inflammation index and systemic inflammation response index with diabetic kidney disease in patients with type 2 diabetes mellitus","volume":"17","author":"Liu","year":"2024","journal-title":"Diabetes Metab Syndr Obes"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1307692","article-title":"Association of systemic immune-inflammation index with diabetic kidney disease in patients with type 2 diabetes: a cross-sectional study in Chinese population","volume":"14","author":"Yan","year":"2024","journal-title":"Front Endocrinol (Laus)"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1071465","article-title":"Systemic immune-inflammation index is associated with diabetic kidney disease in Type 2 diabetes mellitus patients: Evidence from NHANES 2011-2018","volume":"13","author":"Guo","year":"2022","journal-title":"Front Endocrinol (Laus)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-024-09915-8","article-title":"Prolactin: structure, receptors, and functions","volume":"25","author":"Chasseloup","year":"2024","journal-title":"Rev Endocr Metab Disord"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2024.103643","article-title":"Prolactin\u2019s paradox: Friend, foe, or both in immune regulation","volume":"23","author":"Borba","year":"2024","journal-title":"Autoimmun Rev"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e15490","DOI":"10.14814\/phy2.15490","article-title":"Sex hormones and the risk of cardiovascular disease and mortality in male and female patients with chronic kidney disease: A systematic review and meta-analysis","volume":"10","author":"Oh","year":"2022","journal-title":"Physiol Rep"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2215\/cjn.06840711","article-title":"Prolactin levels, endothelial dysfunction, and the risk of cardiovascular events and mortality in patients with CKD","volume":"7","author":"Carrero","year":"2012","journal-title":"Clin J Am Soc Nephrol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1080\/0886022x.2023.2284211","article-title":"Astragalus polysaccharide promotes autophagy and alleviates diabetic nephropathy by targeting the lncRNA Gm41268\/PRLR pathway","volume":"45","author":"Chen","year":"2023","journal-title":"Ren Fail"},{"key":"B27","article-title":"Prolactin receptor mRNA expression in experimental diabetic nephropathy: Relationship with urinary albumin excretion","volume":"36","author":"Al-Trad","year":"2015","journal-title":"Neuro Endocrinol Lett"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"105","author":"Stevens","year":"2024","journal-title":"Kidney Int"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2337\/dc25-S002","article-title":"Diagnosis and classification of diabetes: standards of care in diabetes\u20142025","volume":"48","author":"ElSayed","year":"2025","journal-title":"Diabetes Care"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2013.12.006","article-title":"GFR estimation: from physiology to public health","volume":"63","author":"Levey","year":"2014","journal-title":"Am J Kidney Dis"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1190934","article-title":"Chinese guideline for lipid management","volume":"14","author":"Li","year":"2023","journal-title":"Front Pharmacol"},{"key":"B32","volume-title":"Guideline on haemoglobin cutoffs to define anaemia in individuals and populations","year":"2024"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-019-1782-x","article-title":"Systemic immune-inflammation index predicts prognosis of patients with advanced pancreatic cancer","volume":"17","author":"Zhang","year":"2019","journal-title":"J Transl Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1097\/sla.0000000000003370","article-title":"High systemic immune-inflammation index is an adverse prognostic factor for patients with gastroesophageal adenocarcinoma","volume":"273","author":"Jomrich","year":"2021","journal-title":"Ann Surg"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1080\/08941939.2022.2084187","article-title":"Systemic inflammation response index and systemic immune inflammation index are associated with clinical outcomes in patients with acute pancreatitis","volume":"35","author":"Biyik","year":"2022","journal-title":"J Invest Surg"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.865244","article-title":"Systemic-immune-inflammation index as a promising biomarker for predicting perioperative ischemic stroke in older patients who underwent non-cardiac surgery","volume":"14","author":"Zhang","year":"2022","journal-title":"Front Aging Neurosci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-024-01959-5","article-title":"Systemic immune inflammation index with all-cause and cause-specific mortality: a meta-analysis","volume":"73","author":"Li","year":"2024","journal-title":"Inflammation Res"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.semnephrol.2021.03.010","article-title":"Prolactin and other pituitary disorders in kidney disease","volume":"41","author":"Huang","year":"2021","journal-title":"Semin Nephrol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26136347","article-title":"The interplay of prolactin with inflammatory nutritional markers and NT-proBNP in chronic kidney disease","volume":"26","author":"Rusu","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-87783-1","article-title":"Prolactin levels and chronic kidney disease and the subsequent risk of cardiovascular events: A long term population based cohort study","volume":"15","author":"Rojhani","year":"2025","journal-title":"Sci Rep"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxm145","article-title":"Prolactin-induced production of cytokines in macrophages in vitro involves JAK\/STAT and JNK MAPK pathways","volume":"20","author":"Tripathi","year":"2008","journal-title":"Int Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1496610","article-title":"Elevated levels of exogenous prolactin promote inflammation at the maternal-fetal interface via the JAK2\/STAT5B signaling axis","volume":"15","author":"Williams","year":"2024","journal-title":"Front Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2023.156253","article-title":"The effects of prolactin on the immune system, its relationship with the severity of COVID-19, and its potential immunomodulatory therapeutic effect","volume":"169","author":"Rasmi","year":"2023","journal-title":"Cytokine"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-018-0059-4","article-title":"Inflammaging: a new immune-metabolic viewpoint for age-related diseases","volume":"14","author":"Franceschi","year":"2018","journal-title":"Nat Rev Endocrinol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.116.303697","article-title":"Inflammation, immunity, and hypertensive end-organ damage","volume":"116","author":"McMaster","year":"2015","journal-title":"Circ Res"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1772810\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T11:08:27Z","timestamp":1772449707000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1772810\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,2]]},"references-count":45,"alternative-id":["10.3389\/fendo.2026.1772810"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1772810","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,2]]},"article-number":"1772810"}}