{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T05:44:33Z","timestamp":1774849473586,"version":"3.50.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012620","name":"Taishan Scholar Foundation of Shandong Province","doi-asserted-by":"publisher","award":["tsqn202312382"],"award-info":[{"award-number":["tsqn202312382"]}],"id":[{"id":"10.13039\/100012620","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82370890, 32470636"],"award-info":[{"award-number":["82370890, 32470636"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018627","name":"Science and Technology Support Plan for Youth Innovation of Colleges and Universities of Shandong Province of China","doi-asserted-by":"publisher","award":["2023KJ224"],"award-info":[{"award-number":["2023KJ224"]}],"id":[{"id":"10.13039\/501100018627","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the association between serum cystatin C (CysC) levels and tophus presence, and to assess its diagnostic value for structural joint damage in gout.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this cross-sectional study of 598 gout patients, we examined the association between serum CysC and both the presence and burden of tophi. The predictive value of CysC for tophus and bone erosion was further evaluated using logistic regression and ROC curve analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Elevated serum CysC levels were significantly associated with older age, longer disease duration, and an increased prevalence of tophus, bone erosion, and the patients in the highest quartile (Q4, &amp;gt;1.28 mg\/L) had a 3.87-fold higher adjusted odds of tophus (P &amp;lt; 0.05), showing a significant dose\u2013response trend (P for trend = 0.003). Serum CysC alone demonstrated a moderate predictive value for tophus (AUC\u00a0=\u00a00.627), which improved in multivariable models (AUC\u00a0=\u00a00.777). A similar enhancement in predictive performance was noted for bone erosion (fully adjusted AUC, 0.756). There was a significant interaction between serum CysC and magnesium regarding tophus risk (P &amp;lt; 0.001). Furthermore, multivariate ordinal regression analysis identified higher CysC, longer gout duration, bone erosion, and the double contour sign as independent predictors of tophus burden.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Serum CysC independently predicts tophus in gout and shows interaction with serum magnesium. Its integration into risk assessment may improve clinical stratification and support timely, individualized treatment strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1733216","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T04:12:35Z","timestamp":1774843955000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated serum cystatin C predicts tophus formation in gout: evidence from a cross-sectional study"],"prefix":"10.3389","volume":"17","author":[{"given":"Yonglu","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengqian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]},{"name":"Shandong Provincial Clinical Research Center for Immune Diseases, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aichang","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]},{"name":"Shandong Provincial Clinical Research Center for Immune Diseases, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingzi","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University","place":["Qingdao, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s2665-9913(24)00117-6","article-title":"Global, regional, and national burden of gout, 1990-2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021","volume":"6","author":"Cross","year":"2024","journal-title":"Lancet Rheumatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/med\/9780199642489.003.0141","article-title":"Gout","volume":"397","author":"Dalbeth","year":"2021","journal-title":"Lancet (Lond Engl)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3238\/arztebl.2017.0215","article-title":"Treatment options for gout","volume":"114","author":"Engel","year":"2017","journal-title":"Deutsches Arzteblatt Int"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/keaf347","article-title":"Mapping monosodium urate crystal deposition within metatarsophalangeal joints in tophaceous gout: a dual-energy CT study","volume":"64","author":"De Silva","year":"2025","journal-title":"Rheumatol (Oxford Engl)"},{"key":"B5","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/ki.1975.81","article-title":"Editorial: An evaluation of the pathogenesis of gouty kidney","volume":"8","author":"Emmerson","year":"1975","journal-title":"Kidney Int"},{"key":"B6","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/0049-0172(77)90016-6","article-title":"The gouty kidney","volume":"7","author":"Bluestone","year":"1977","journal-title":"Semin Arthritis Rheumatism"},{"key":"B7","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1186\/s13075-015-0610-9","article-title":"Gout and risk of chronic kidney disease and nephrolithiasis: meta-analysis of observational studies","volume":"17","author":"Roughley","year":"2015","journal-title":"Arthritis Res Ther"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1186\/ar3806","article-title":"Risk of end-stage renal disease associated with gout: a nationwide population study","volume":"14","author":"Yu","year":"2012","journal-title":"Arthritis Res Ther"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000069700.62727.c5","article-title":"Is there a pathogenetic role for uric acid in hypertension and cardiovascular and renal disease","volume":"41","author":"Johnson","year":"2003","journal-title":"Hyperten (Dallas Tex: 1979)"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejim.2020.07.006","article-title":"Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease","volume":"80","author":"Borghi","year":"2020","journal-title":"Eur J Internal Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2023.3241","article-title":"Prevalence and overlap of cardiac, renal, and metabolic conditions in US adults, 1999-2020","volume":"8","author":"Ostrominski","year":"2023","journal-title":"JAMA Cardiol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27716","article-title":"Cystatin C as biomarker for the evaluation of renal outcome in AL amyloidosis","volume":"100","author":"Theodorakakou","year":"2025","journal-title":"Am J Hematol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1136\/adc.82.1.71","article-title":"Reference ranges for plasma cystatin C and creatinine measurements in premature infants, neonates, and older children","volume":"82","author":"Finney","year":"2000","journal-title":"Arch Dis Childh"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2012.169","article-title":"Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C","volume":"82","author":"Schwartz","year":"2012","journal-title":"Kidney Int"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2010.02.337","article-title":"Estimating GFR using the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation: more accurate GFR estimates, lower CKD prevalence estimates, and better risk predictions","volume":"55","author":"Levey","year":"2010","journal-title":"Am J Kidney Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/art.39254","article-title":"2015 Gout Classification Criteria: an American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"67","author":"Neogi","year":"2015","journal-title":"Arthritis Rheumatol (Hoboken NJ)"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1177\/0148607112440285","article-title":"Consensus statement: Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition)","volume":"36","author":"White","year":"2012","journal-title":"JPEN J Parenteral Enteral Nutr"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/art.40929","article-title":"Effects of allopurinol dose escalation on bone erosion and urate volume in gout: a dual-energy computed tomography imaging study within a randomized, controlled trial","volume":"71","author":"Dalbeth","year":"2019","journal-title":"Arthritis Rheumatol (Hoboken NJ)"},{"key":"B19","doi-asserted-by":"publisher","first-page":"Itc33","DOI":"10.7326\/annals-24-03951","article-title":"Gout","volume":"178","author":"FitzGerald","year":"2025","journal-title":"Ann Internal Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-14-363","article-title":"Reduced creatinine clearance is associated with early development of subcutaneous tophi in people with gout","volume":"14","author":"Dalbeth","year":"2013","journal-title":"BMC Musculosk Disord"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.2337\/figshare.28550720.v1","article-title":"Comparison of serum creatinine- and cystatin C-based eGFR at baseline and their prediction of incident moderate albuminuria in individuals with type 1 diabetes","volume":"48","author":"Harjutsalo","year":"2025","journal-title":"Diabetes Care"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2016.09.016","article-title":"Plasma cystatin C and neutrophil gelatinase-associated lipocalin in relation to coronary atherosclerosis on intravascular ultrasound and cardiovascular outcome: impact of kidney function (ATHEROREMO-IVUS study)","volume":"254","author":"Brankovic","year":"2016","journal-title":"Atherosclerosis"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2024.111355","article-title":"Electrochemical and optical methods for detection of cystatin C as a biomarker of kidney disease","volume":"406","author":"Zhang","year":"2025","journal-title":"Chem Biol Interact"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2024.10.025","article-title":"Activating soluble guanylyl cyclase attenuates ischemic kidney damage","volume":"107","author":"Lichtenberger","year":"2025","journal-title":"Kidney Int"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/jci28075","article-title":"MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals","volume":"116","author":"Chen","year":"2006","journal-title":"J Clin Invest"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2025.04.007","article-title":"Targeting the NLRP3 inflammasome for inflammatory disease therapy","volume":"46","author":"Cabral","year":"2025","journal-title":"Trends Pharmacol Sci"},{"key":"B27","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.imlet.2018.01.006","article-title":"Involvement of cystatin C in immunity and apoptosis","volume":"196","author":"Zi","year":"2018","journal-title":"Immunol Lett"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26136086","article-title":"The relationship between kidney biomarkers, inflammation, severity, and mortality due to COVID-19-a two-timepoint study","volume":"26","author":"Tozoni","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgae225","article-title":"Cystatin C is a predictor for long-term, all-cause, and cardiovascular mortality in US adults with metabolic syndrome","volume":"109","author":"Song","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1423227","article-title":"The predictive value of the triglyceride glucose index combined with cystatin C for the prognosis of patients with acute coronary syndrome","volume":"15","author":"Wang","year":"2024","journal-title":"Front Endocrinol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2215\/cjn.00840208","article-title":"Age, gender, and race effects on cystatin C levels in US adolescents","volume":"3","author":"Groesbeck","year":"2008","journal-title":"Clin J Am Soc Nephrol: CJASN"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2885","DOI":"10.1038\/s41467-021-23005-2","article-title":"TRPM7 kinase-mediated immunomodulation in macrophage plays a central role in magnesium ion-induced bone regeneration","volume":"12","author":"Qiao","year":"2021","journal-title":"Nat Commun"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1375871","article-title":"Serum ionized magnesium acts as an independent protective factor against bone erosion in patients with gouty arthritis: a cross-sectional study","volume":"15","author":"Li","year":"2024","journal-title":"Front Endocrinol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/s12011-025-04638-6","article-title":"The relationship between magnesium depletion score and kidney stone risk in gout patients: a mediation analysis","volume":"203","author":"Liu","year":"2025","journal-title":"Biol Trace Elem Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1097\/js9.0000000000001822","article-title":"Association between magnesium depletion score and the prevalence of kidney stones in the low primary income ratio: a cross-sectional study of NHANES 2007-2018","volume":"110","author":"Wang","year":"2024","journal-title":"Int J Surg (Lond Engl)"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1733216\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T04:12:42Z","timestamp":1774843962000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1733216\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,30]]},"references-count":35,"alternative-id":["10.3389\/fendo.2026.1733216"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1733216","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,30]]},"article-number":"1733216"}}