{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T12:25:15Z","timestamp":1772022315848,"version":"3.50.1"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T00:00:00Z","timestamp":1666828800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Only two previous studies in systemic lupus erythematosus (SLE) patients have identified that the blood concentrations of uromodulin are lower in nephritis. However, none of them had evaluated whether a low serum uromodulin adjusted by the glomerular filtration rate (sUromod\/eGFR index) contributed to identify patients in risk of lupus nephritis (LN) using multivariable models.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Aim<\/jats:title>\n<jats:p>Therefore, this study aimed two objectives to evaluate the association between low serum uromodulin levels and low sUromod adjusted by eGFR with renal flares in SLE excluding effects of potential confounders in multivariable analyses; and to identify the value of low sUmod and low sUmod\/eGFR index as a potential diagnostic marker of LN.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Patients and methods<\/jats:title>\n<jats:p>Design: Cross-sectional study. SLE patients (n = 114) were investigated for lupus flare with renal SLEDAI. Two groups: a) SLE with renal flare (renal-SLEDAI\u22654, n = 41) and b) SLE non-renal flare (renal SLEDAI&lt;4, n = 73). SLE patients were evaluated by other indices including a global disease activity index (SLEDAI) and SLICC renal disease activity score. Serum uromodulin levels (ng\/mL) were quantified by ELISA. Serum uromodulin was adjusted by eGFR (sUromod\/eGFR index). Cutt-offs of low sUromodulin and low sUromod\/eGFR index were computed, ROC curves were performed and values of diagnostic tests were obtained. Multivariable logistic regression models were performed to identify if low sUromod\/eGFR index is associated to renal flares.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>Low serum uromodulin and low sUromod\/eGFR index correlated to high scores of renal-SLEDAI, SLICC-renal and proteinuria. SLE patients with a renal flare had lower uromodulin levels compared to SLE patients without renal flare (p = 0.004). After adjusting by potential confounders, the low sUromod\/eGFR index (&lt;0.80 ng\/mL) increased the risk of a renal flare (OR, 2.91; 95%CI, 1.21 to 6.98; p = 0.02).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We propose the low sUromod\/eGFR index as a potential new marker of renal disease activity in SLE.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0276481","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T17:33:02Z","timestamp":1666891982000},"page":"e0276481","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Low serum uromodulin levels and their association with lupus flares"],"prefix":"10.1371","volume":"17","author":[{"given":"Bonilla-Lara","family":"David","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gamez-Nava Jorge","family":"Ivan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Perez-Guerrero Edsaul","family":"Emilio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Murillo-Saich Jessica","family":"Daniela","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Contreras-Haro","family":"Betsabe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vazquez-Villegas Maria","family":"Luisa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fajardo-Robledo Nicte","family":"Selene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aguilar-Chavez Erika 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Ernesto","family":"German","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6517-6344","authenticated-orcid":true,"given":"Laura","family":"Gonzalez-Lopez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2022,10,27]]},"reference":[{"key":"pone.0276481.ref001","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1093\/rheumatology\/kev311","article-title":"The frequency and outcome of lupus nephritis: Results from an international inception cohort study","volume":"55","author":"JG Hanly","year":"2015","journal-title":"Rheumatology (United Kingdom)"},{"key":"pone.0276481.ref002","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1177\/0961203316686700","article-title":"Outcome in biopsy-proven Lupus nephritis: Evaluation of biopsies from the Norwegian Kidney Biopsy 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A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE","volume":"35","author":"C Bombardier","year":"1992","journal-title":"Arthritis Rheum"},{"key":"pone.0276481.ref019","doi-asserted-by":"crossref","first-page":"1784","DOI":"10.1002\/art.23456","article-title":"Systemic lupus international collaborating clinics renal activity\/response exercise: Development of a renal activity score and renal response index","volume":"58","author":"M Petri","year":"2008","journal-title":"Arthritis Rheum"},{"key":"pone.0276481.ref020","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1002\/art.1780390303","article-title":"The development and initial validation of the Systemic Lupus International Collaborating Clinics\/American College of Rheumatology damage index for systemic lupus erythematosus","volume":"39","author":"D Gladman","year":"1996","journal-title":"Arthritis Rheum"},{"key":"pone.0276481.ref021","doi-asserted-by":"crossref","first-page":"32","DOI":"10.4103\/1319-2442.279959","article-title":"Study of the Relationship between Urinary Level of Uromodulin, Renal Involvement and Disease Activity in Patients with Systemic Lupus Erythrematosus","volume":"31","author":"R Nabil Bedair","year":"2020","journal-title":"Saudi J Kidney Dis Transpl"},{"key":"pone.0276481.ref022","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1681\/ASN.V102413","article-title":"Lupus Nephritis","volume":"10","author":"JS Cameron","year":"1999","journal-title":"JASN"},{"key":"pone.0276481.ref023","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1007\/s12016-010-8197-z","article-title":"Urinary biomarkers in lupus nephritis","volume":"40","author":"J Reyes-Thomas","year":"2011","journal-title":"lin Rev Allergy Immunol"},{"key":"pone.0276481.ref024","article-title":"Combined Use of Serum Uromodulin and eGFR to Estimate Mortality Risk","volume":"8","author":"B Yazdani","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"pone.0276481.ref025","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1191\/0961203305lu2059oa","article-title":"Lupus nephritis flares","volume":"14","author":"PI Sidiropoulos","year":"2005","journal-title":"Lupus"},{"key":"pone.0276481.ref026","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1080\/1744666X.2018.1538789","article-title":"Mortality in systemic lupus erythematosus: causes, predictors and interventions","volume":"14","author":"V Ocampo-Piraquive","year":"2018","journal-title":"Expert Rev Clinical Immunol"},{"key":"pone.0276481.ref027","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1097\/BOR.0b013e32832efff1","article-title":"Pathogenesis of kidney disease in systemic lupus erythematosus","volume":"21","author":"H Bagavant","year":"2009","journal-title":"Curr Opin 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