{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T21:18:01Z","timestamp":1778793481521,"version":"3.51.4"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"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":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Diabetic kidney disease (DKD) is linked to immunity and inflammation. We aimed to investigate if systemic inflammatory indicators can predict mortality in DKD patients in intensive care units (ICUs) and determine potential associations between them.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study included a cohort of 840 adults with DKD in the ICU. Three systemic inflammatory indicators were evaluated by peripheral blood tests: systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR). Cox regression analysis, restricted cubic spline (RCS), and Kaplan-Meier curves were used to evaluate the associations between the inflammatory indicators and the mortality of the DKD population. Receiver operating characteristic (ROC) was employed to ascertain the predictive accuracy of varied systemic inflammatory indicators.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After adjusting for all covariates, Cox regression analysis showed that inflammatory indicators were all significantly positively associated with 28-day mortality (SII: HR 1.39, 95% CI, 1.16-1.67, <jats:italic>P<\/jats:italic>&amp;lt;0.001; SIRI: HR 1.36, 95% CI, 1.14-1.62, <jats:italic>P<\/jats:italic>=0.001; NLR: HR 1.48, 95% CI, 1.20-1.84, <jats:italic>P<\/jats:italic>&amp;lt;0.001). Compared with the lowest tertile (tertile 1), participants in the highest tertile (tertile 3) had significantly increased risk of 28-day mortality (SII: HR 2.46, 95% CI, 1.51-4.02, <jats:italic>P<\/jats:italic>&amp;lt;0.001; SIRI: HR 3.31, 95% CI, 1.87-5.84, <jats:italic>P<\/jats:italic>&amp;lt;0.001; NLR: HR 3.42, 95% CI, 1.94-6.03, <jats:italic>P<\/jats:italic>&amp;lt;0.001). Furthermore, ROC curves showed that NLR and SIRI had higher predictive values than SII (NLR<jats:sub>AUC<\/jats:sub> vs. SII<jats:sub>AUC<\/jats:sub>: 0.681 vs. 0.633, <jats:italic>P<\/jats:italic>=0.006; SIRI<jats:sub>AUC<\/jats:sub> vs. SII<jats:sub>AUC<\/jats:sub>: 0.675 vs. 0.633, <jats:italic>P<\/jats:italic>=0.041) in predicting 28-day mortality.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study demonstrated that systemic inflammatory indicators (SII, SIRI, and NLR) were positively associated with 28-day and 365-day mortality in critically ill patients with DKD. Inflammatory indicators may serve as predictors of mortality in critically ill DKD patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1503667","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T05:47:14Z","timestamp":1748584034000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Association between systemic inflammatory indicators on admission and mortality in critically ill patients with diabetic kidney disease based on the MIMIC-IV database: a cohort study"],"prefix":"10.3389","volume":"16","author":[{"given":"Guo-Yin","family":"Shen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian-Qian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si-Ang","family":"Lv","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuo-Deng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ru-Lin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ackd.2017.10.011","article-title":"The global epidemiology of diabetes and kidney disease","volume":"25","author":"Koye","year":"2018","journal-title":"Adv Chronic Kidney D"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2021-002125","article-title":"Burden of chronic kidney disease and rapid decline in renal function among adults attending a hospital-based diabetes center in northern europe","volume":"9","author":"Griffin","year":"2021","journal-title":"BMJ Open Diabetes Res Care"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2147\/DMSO.S408170","article-title":"Translation animal models of diabetic kidney disease: biochemical and histological phenotypes, advantages and limitations","volume":"16","author":"Luo","year":"2023","journal-title":"Diabetes Metab Syndr Obes: Targets Ther"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2019.10.005","article-title":"Diabetic kidney diseases revisited: A new perspective for a new era","volume":"30","author":"Fu","year":"2019","journal-title":"Mol Metab"},{"key":"B5","unstructured":"Association of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio with diabetic kidney disease in chinese patients with type 2 diabetes: a cross-sectional study"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-024-00827-z","article-title":"Combination therapy for kidney disease in people with diabetes mellitus","volume":"20","author":"van Raalte","year":"2024","journal-title":"Nat Rev Nephrol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063086","article-title":"Recent advances in the management of diabetic kidney disease: slowing progression","volume":"25","author":"Wang","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1007\/s00125-018-4567-5","article-title":"Biomarkers of diabetic kidney disease","volume":"61","author":"Colhoun","year":"2018","journal-title":"Diabetologia"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2022.10.030","article-title":"Targeting inflammation to treat diabetic kidney disease: the road to 2030","volume":"103","author":"Rayego-Mateos","year":"2023","journal-title":"Kidney Int"},{"key":"B10","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: Targets Ther"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S503648","article-title":"Inflammatory indices and MAFLD prevalence in hypertensive patients: a large-scale cross-sectional analysis from China","volume":"18","author":"Shen","year":"2025","journal-title":"J Inflammation Res"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1080\/00325481.2024.2354158","article-title":"Association of systemic inflammatory response index with bone mineral density, osteoporosis, and future fracture risk in elderly hypertensive patients","volume":"136","author":"Ma","year":"2024","journal-title":"Postgrad Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v23.i34.6261","article-title":"Systemic immune-inflammation index for predicting prognosis of colorectal cancer","volume":"23","author":"Chen","year":"2017","journal-title":"World J Gastroentero"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1115031","article-title":"The clinical value of neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) for predicting the occurrence and severity of pneumonia in patients with intracerebral hemorrhage","volume":"14","author":"Wang","year":"2023","journal-title":"Front Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e2619","DOI":"10.1002\/brb3.2619","article-title":"Prognostic value of the systemic inflammation response index in patients with acute ischemic stroke","volume":"12","author":"Zhou","year":"2022","journal-title":"Brain Behav"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1159\/000524759","article-title":"Predictive ability of systemic inflammation response index for the risk of pneumonia in patients with acute ischemic stroke","volume":"69","author":"Yan","year":"2023","journal-title":"Gerontology"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcha.2024.101372","article-title":"Association between inflammation markers and all-cause mortality in critical ill patients with atrial fibrillation: analysis of the multi-parameter intelligent monitoring in intensive care (MIMIC-IV) database","volume":"51","author":"Li","year":"2024","journal-title":"Int J Cardiol Heart Vasc"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S433190","article-title":"Systemic inflammation response index as a predictor of stroke risk in elderly patients with hypertension: A cohort study","volume":"16","author":"Cai","year":"2023","journal-title":"J Inflammation Res"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2022.893683","article-title":"Association between wait time of central venous pressure measurement and outcomes in critical patients with acute kidney injury: a retrospective cohort study","volume":"10","author":"Yang","year":"2022","journal-title":"Front Public Health"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.918657","article-title":"Identification of diagnostic gene biomarkers and immune infiltration in patients with diabetic kidney disease using machine learning strategies and bioinformatic analysis","volume":"9","author":"Fu","year":"2022","journal-title":"Front Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.3390\/antiox13040396","article-title":"Endothelial NOX5 obliterates the reno-protective effect of Nox4 deletion by promoting renal fibrosis via activation of EMT and ROS-sensitive pathways in diabetes","volume":"13","author":"Jandeleit-Dahm","year":"2024","journal-title":"Antioxidants (Basel)"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-022-01919-y","article-title":"Development and validation of a risk score for diabetic kidney disease prediction in type 2 diabetes patients: a machine learning approach","volume":"46","author":"Hosseini Sarkhosh","year":"2023","journal-title":"J Endocrinol Invest"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12051098","article-title":"Diabetes and renal complications: an overview on pathophysiology, biomarkers and therapeutic interventions","volume":"12","author":"Jha","year":"2024","journal-title":"Biomedicines"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfad194","article-title":"Cardiovascular risk due to diabetes mellitus in patients with chronic kidney disease-prospective data from the german chronic kidney disease cohort","volume":"16","author":"Ruhe","year":"2023","journal-title":"Clin Kidney J"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-024-01861-0","article-title":"Association of systemic immune-inflammation index and systemic inflammation response index with chronic kidney disease: observational study of 40,937 adults","volume":"73","author":"Huang","year":"2024","journal-title":"Inflammation Res"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1338025","article-title":"Systemic inflammatory response index (SIRI) is associated with all-cause mortality and cardiovascular mortality in population with chronic kidney disease: evidence from NHANES (2001-2018)","volume":"15","author":"Gu","year":"2024","journal-title":"Front Immunol"},{"key":"B27","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 (Lausanne)"},{"key":"B28","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":"2023","journal-title":"Front Endocrinol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2147\/dmso.s437580","article-title":"Exploring the correlation between the systemic immune inflammation index (SII), systemic inflammatory response index (SIRI), and type 2 diabetic retinopathy","volume":"16","author":"Wang","year":"2023","journal-title":"Diabetes Metab Syndr Obes : Targets Ther"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1365591","article-title":"Association between systemic inflammatory indicators with the survival of chronic kidney disease: a prospective study based on NHANES","volume":"15","author":"Chen","year":"2024","journal-title":"Front Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/4729019","article-title":"Circulating expression level of lncRNA malat1 in diabetic kidney disease patients and its clinical significance","volume":"2020","author":"Lj","year":"2020","journal-title":"J Diabetes Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-022-03354-7","article-title":"Novel biomarkers for prognosticating diabetic kidney disease progression","volume":"55","author":"Swaminathan","year":"2023","journal-title":"Int Urol Nephrol"},{"key":"B33","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":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-024-05066-1","article-title":"Tirzepatide alleviates oxidative stress and inflammation in diabetic nephropathy via IL-17 signaling pathway","volume":"480","author":"Yang","year":"2024","journal-title":"Mol Cell Biochem"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1111\/1753-0407.13292","article-title":"Increased neutrophil count is associated with the development of chronic kidney disease in patients with diabetes","volume":"14","author":"Zhang","year":"2022","journal-title":"J Diabetes"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21113798","article-title":"Pathogenic pathways and therapeutic approaches targeting inflammation in diabetic nephropathy","volume":"21","author":"Rayego-Mateos","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.835879","article-title":"Excessive activation of notch signaling in macrophages promote kidney inflammation, fibrosis, and necroptosis","volume":"13","author":"Ma","year":"2022","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121991","article-title":"Macrophage-derived exosomes promote activation of NLRP3 inflammasome and autophagy deficiency of mesangial cells in diabetic nephropathy","volume":"330","author":"Liu","year":"2023","journal-title":"Life Sci"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107413","article-title":"Association of platelet-to-lymphocyte ratio with kidney clinicopathologic features and renal outcomes in patients with diabetic kidney disease","volume":"93","author":"Duan","year":"2021","journal-title":"Int Immunopharmacol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2019.05.008","article-title":"Modulation of megakaryopoiesis and platelet production during inflammation","volume":"179","author":"Couldwell","year":"2019","journal-title":"Thromb Res"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23158270","article-title":"The role of platelets in diabetic kidney disease","volume":"23","author":"Rustiasari","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01731","article-title":"Platelets and immune responses during thromboinflammation","volume":"10","author":"Mezger","year":"2019","journal-title":"Front Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2022-069027","article-title":"Association between minimal decrease in platelet counts and outcomes in septic patients: a retrospective observational study","volume":"13","author":"Liu","year":"2023","journal-title":"BMJ Open"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2022.2131753","article-title":"Diagnostic and prognostic role of platelets in patients with sepsis and septic shock","volume":"34","author":"Schupp","year":"2023","journal-title":"Platelets"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.5005\/jp-journals-10071-23574","article-title":"Platelet indices as predictive markers of prognosis in critically ill patients: a prospective study","volume":"24","author":"Samuel","year":"2020","journal-title":"Indian J Crit Care Med: Peer-Rev Off Publ Indian Soc Crit Care Med"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000005886","article-title":"Systemic immune-inflammation index (SII) is a useful prognostic indicator for patients with squamous cell carcinoma of the esophagus","volume":"96","author":"Feng","year":"2017","journal-title":"Medicine"},{"key":"B47","doi-asserted-by":"publisher","first-page":"6578","DOI":"10.1038\/s41598-024-57343-0","article-title":"Systemic immune-inflammation index as a prognostic marker in HER2-positive breast cancer patients undergoing trastuzumab therapy","volume":"14","author":"Pang","year":"2024","journal-title":"Sci Rep"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1303132","article-title":"Prognostic and clinicopathological role of pretreatment systemic immune-inflammation index in patients with oral squamous cell carcinoma: a meta-analysis","volume":"13","author":"Zhang","year":"2023","journal-title":"Front Oncol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-022-00733-9","article-title":"Systemic immune inflammation index and system inflammation response index are potential biomarkers of atrial fibrillation among the patients presenting with ischemic stroke","volume":"27","author":"Lin","year":"2022","journal-title":"Eur J Med Res"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23179553","article-title":"Investigation of the associations of novel inflammatory biomarkers\u2014systemic inflammatory index (SII) and systemic inflammatory response index (SIRI)\u2014with the severity of coronary artery disease and acute coronary syndrome occurrence","volume":"23","author":"Dziedzic","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2023.1174711","article-title":"Prognostic value of inflammatory markers for in-hospital mortality in intensive care patients with acute ischemic stroke: a retrospective observational study based on MIMIC-IV","volume":"14","author":"Hu","year":"2023","journal-title":"Front Neurol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1503667\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T05:47:21Z","timestamp":1748584041000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1503667\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,30]]},"references-count":51,"alternative-id":["10.3389\/fendo.2025.1503667"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1503667","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,30]]},"article-number":"1503667"}}