{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:31:11Z","timestamp":1788827471349,"version":"build-2803163510"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T00:00:00Z","timestamp":1780358400000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Urinary albumin-to-creatinine ratio (UACR) is a key marker for monitoring proteinuria progression in type 2 diabetes mellitus (T2DM). However, UACR trajectory patterns and their association with proteinuria risk remain underexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study included 3,101 T2DM patients (baseline UACR &amp;lt;30 mg\/g) with regular follow-up from March 2018 to October 2024 at the Ningbo Metabolic Management Center (MMC) subcenter. Clinical data were obtained from electronic medical records. Group-based trajectory modeling (GBTM) identified UACR trajectory patterns. Partial Least Squares Discriminant Analysis (PLS-DA) with Boruta algorithm selected key variables associated with trajectories. Additionally, we used the Light Gradient Boosting Machine (LightGBM) algorithm for multi-class classification modeling and Shapley Additive exPlanations (SHAP) values to quantify individual feature contributions to distinct trajectories. Multivariable Cox regression evaluated proteinuria risk by trajectory.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>GBTM analysis identified three distinct UACR trajectories: low-normal, mid-range normal, and rising with fluctuation groups. PLS-DA with Boruta algorithm selected 11 significant features, including baseline UACR, sex, height, Hb, HCT, BMI, waist circumference, RBC, FCP, SCR, and FINS. Meanwhile, we explained the prediction results of a multi-class LightGBM model by assigning SHAP values to 11 features. Multivariable Cox regression showed significantly increased proteinuria risk in both mid-range normal (HR = 48.40, 95% CI: 14.67-159.67) and rising with fluctuation groups (HR = 509.56, 95% CI: 157.01\u20131653.70) compared to low-normal group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Identifying distinct UACR trajectories in Chinese T2DM patients, particularly the strong association between rising with fluctuation pattern and proteinuria risk, indicates that trajectory-informed patient classification could enhance early-stage diabetic kidney disease screening and preventive strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1833972","type":"journal-article","created":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:28:07Z","timestamp":1780374487000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Longitudinal trajectories of urinary albumin-to-creatinine ratio and risk of proteinuria among Chinese patients with type 2 diabetes: a single\u2212center retrospective cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Qian","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital of Ningbo University","place":["Ningbo, Zhejiang, China"]},{"name":"Department of Medical Record Statistics, The First Affiliated Hospital of Ningbo University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tieqiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital of Ningbo University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqing","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Zhenhai District People\u2019s Hospital","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiankai","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Beilun District People\u2019s Hospital","place":["Ningbo, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital of Ningbo University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushan","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital of Ningbo University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqing","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, The First Affiliated Hospital of Ningbo University","place":["Ningbo, Zhejiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.16183","article-title":"Trends and analysis of risk factor differences in the global burden of chronic kidney disease due to type 2 diabetes from 1990 to 2021: a population-based study","volume":"27","author":"Wang","year":"2025","journal-title":"Diabetes Obes Metab"},{"key":"B2","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 Dis"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.11491116","article-title":"Diabetic kidney disease: challenges, progress, and possibilities","volume":"12","author":"Alicic","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.115.306884","article-title":"Vascular complications of diabetes","volume":"118","author":"Beckman","year":"2016","journal-title":"Circ Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/nejmc1602469","article-title":"Trends in chronic kidney disease in China","volume":"375","author":"Zhang","year":"2016","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12104","article-title":"Pathophysiology of proteinuria and its value as an outcome measure in chronic kidney disease","volume":"76","author":"Cravedi","year":"2013","journal-title":"Br J Clin Pharmacol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.39","article-title":"Relation between kidney function, proteinuria, and adverse outcomes","volume":"303","author":"Hemmelgarn","year":"2010","journal-title":"JAMA"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-1622","article-title":"Changes in albuminuria predict cardiovascular and renal outcomes in type 2 diabetes: a Post Hoc analysis of the LEADER trial","volume":"44","author":"Persson","year":"2021","journal-title":"Diabetes Care"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2021-002241","article-title":"Two-year longitudinal trajectory patterns of albuminuria and subsequent rates of end-stage kidney disease and all-cause death: a nationwide cohort study of biopsy-proven diabetic kidney disease","volume":"9","author":"Yamanouchi","year":"2021","journal-title":"BMJ Open Diabetes Res Care"},{"key":"B10","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1146\/annurev-clinpsy-081122-012416","article-title":"Recent advances in group-based trajectory modeling for clinical research","volume":"20","author":"Nagin","year":"2024","journal-title":"Annu Rev Clin Psychol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15856","article-title":"Trajectory of haemoglobin A1c and incidence of cardiovascular disease in patients with type 2 diabetes mellitus","volume":"26","author":"Wang","year":"2024","journal-title":"Diabetes Obes Metab"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1355149","article-title":"Association of the longitudinal trajectory of urinary albumin\/creatinine ratio in diabetic patients with adverse cardiac event risk: a retrospective cohort study","volume":"15","author":"Li","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B13","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/agm2.12294","article-title":"Guideline for the management of diabetes mellitus in the elderly in China (2024 edition)","volume":"7","author":"Guo","year":"2024","journal-title":"Aging Med (Milton)"},{"key":"B14","article-title":"KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"105","year":"2024","journal-title":"Kidney Int"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1213\/ane.0000000000005773","article-title":"Statistics from A (agreement) to Z (z score): a guide to interpreting common measures of association, agreement, diagnostic accuracy, effect size, heterogeneity, and reliability in medical research","volume":"133","author":"Schober","year":"2021","journal-title":"Anesth Analg"},{"key":"B16","doi-asserted-by":"crossref","DOI":"10.4159\/9780674041318","volume-title":"Group-based modeling of development","author":"Nagin","year":"2005"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1177\/0962280216673085","article-title":"Group-based multi-trajectory modeling","volume":"27","author":"Nagin","year":"2016","journal-title":"Stat Methods Med Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.patter.2022.100452","article-title":"Shapley variable importance cloud for interpretable machine learning","volume":"3","author":"Ning","year":"2022","journal-title":"Patterns (N Y)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.955241","article-title":"The association between a body shape index and elevated urinary albumin-creatinine ratio in Chinese community adults","volume":"13","author":"Zhang","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/hjh.0000000000001491","article-title":"Predictors for the development of microalbuminuria and interaction with renal function","volume":"35","author":"Chatzikyrkou","year":"2017","journal-title":"J Hypertens"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2022.08.018","article-title":"Predictive markers in chronic kidney disease","volume":"535","author":"Priyadarshini","year":"2022","journal-title":"Clin Chim Acta"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2019.04.069","article-title":"Blood and urine biomarkers in chronic kidney disease: an update","volume":"495","author":"Bidin","year":"2019","journal-title":"Clin Chim Acta"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1172\/jci165654","article-title":"Molecular pathways that drive diabetic kidney disease","volume":"133","author":"Mohandes","year":"2023","journal-title":"J Clin Invest"},{"key":"B24","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s12964-020-00605-x","article-title":"The diabetic microenvironment causes mitochondrial oxidative stress in glomerular endothelial cells and pathological crosstalk with podocytes","volume":"18","author":"Casalena","year":"2020","journal-title":"Cell Commun Signal"},{"key":"B25","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.cmet.2012.01.009","article-title":"Mitochondrial fission triggered by hyperglycemia is mediated by ROCK1 activation in podocytes and endothelial cells","volume":"15","author":"Wang","year":"2012","journal-title":"Cell Metab"},{"key":"B26","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1055\/a-2435-8264","article-title":"Diabetic nephropathy: pathogenesis, mechanisms, and therapeutic strategies","volume":"57","author":"Dwivedi","year":"2025","journal-title":"Horm Metab Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/ki.2008.128","article-title":"Proteinuria in diabetic kidney disease: a mechanistic viewpoint","volume":"74","author":"Jefferson","year":"2008","journal-title":"Kidney Int"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1564847","article-title":"Podocytes in health and glomerular disease","volume":"13","author":"Cunanan","year":"2025","journal-title":"Front Cell Dev Biol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1681\/asn.2016040454","article-title":"Sex differences and renal protection: keeping in touch with your feminine side","volume":"27","author":"Garovic","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1007\/s00467-020-04534-2","article-title":"Nephron number and its determinants: a 2020 update","volume":"36","author":"Charlton","year":"2021","journal-title":"Pediatr Nephrol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/16.3.525","article-title":"Adult height and proteinuria in type 2 diabetes","volume":"16","author":"Fava","year":"2001","journal-title":"Nephrol Dial Transplant"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.2215\/cjn.11111016","article-title":"Diagnosis and management of type 2 diabetic kidney disease","volume":"12","author":"Doshi","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.17002","article-title":"Estimated glomerular filtration rate, albuminuria, and adverse outcomes: an individual-participant data meta-analysis","volume":"330","author":"Grams","year":"2023","journal-title":"JAMA"},{"key":"B34","doi-asserted-by":"publisher","first-page":"3969","DOI":"10.3390\/ijms25073969","article-title":"Molecular targets of novel therapeutics for diabetic kidney disease: a new era of nephroprotection","volume":"25","author":"Mazzieri","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/5584_2020_514","article-title":"Glycaemic control and vascular complications in diabetes mellitus type 2","volume":"1307","author":"Maranta","year":"2021","journal-title":"Adv Exp Med Biol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-021-03035-x","article-title":"Effect of a sodium restriction diet on albuminuria and blood pressure in diabetic kidney disease patients: a meta-analysis","volume":"54","author":"Chen","year":"2022","journal-title":"Int Urol Nephrol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(14)70156-1","article-title":"Effect of a long-term behavioural weight loss intervention on nephropathy in overweight or obese adults with type 2 diabetes: a secondary analysis of the Look AHEAD randomised clinical trial","volume":"2","year":"2014","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03032-4","article-title":"A global initiative to deliver precision health in diabetes","volume":"30","author":"Cefalu","year":"2024","journal-title":"Nat Med"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1833972\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T04:28:08Z","timestamp":1780374488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1833972\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,2]]},"references-count":38,"alternative-id":["10.3389\/fendo.2026.1833972"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1833972","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,2]]},"article-number":"1833972"}}