{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T08:42:57Z","timestamp":1765528977351,"version":"3.48.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100009367","name":"Mansoura University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100009367","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Nephrol"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nephrotic syndrome (NS) is a common pediatric kidney disorder characterized by proteinuria, hypoalbuminemia, and edema. Leukotrienes (LTs), as inflammatory mediators, may contribute to NS pathogenesis and influence treatment response. This study aimed to assess urinary leukotriene E4 (LTE4) levels in children with an initial onset of NS and evaluate their potential as biomarkers for steroid responsiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this observational cohort study, 41 children with a first episode of NS and 41 age- and sex-matched healthy controls were enrolled. Patients were classified into steroid-sensitive NS (SSNS;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200929) and steroid-resistant NS (SRNS;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200912) groups following initial steroid therapy. Urinary LTE4 levels were measured prior to treatment, using enzyme-linked immunosorbent assay (ELISA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Urinary LTE4 levels were significantly elevated in children with NS compared to controls (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.001). Although urinary LTE4 to urinary creatinine (U cr) ratios were also higher in patients, the difference did not reach statistical significance (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.09). No significant correlations were observed between urinary LTE4 levels and urinary protein excretion or serum albumin. Furthermore, urinary LTE4 levels did not significantly differ between SSNS and SRNS groups. A receiver operating characteristic (ROC) curve analysis showed poor predictive value of urinary LTE4 for steroid responsiveness, with area-under-the-curve (AUC) values near 0.5.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>While urinary LTE4 levels are elevated in children with NS, they failed to reliably differentiate between SSNS and SRNS. These findings suggest a limited role for urinary LTE4 as a predictive biomarker of steroid responsiveness in pediatric NS. However, future large-scale studies incorporating both plasma and urinary leukotriene profiles are warranted to validate its role in disease pathogenesis and treatment response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00467-025-06952-6","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T19:19:12Z","timestamp":1759259952000},"page":"101-108","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Urinary leukotriene E4 for predicting steroid sensitivity in children with nephrotic syndrome: an observational cohort study"],"prefix":"10.1007","volume":"41","author":[{"given":"Nehal","family":"Saad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0819-3228","authenticated-orcid":false,"given":"Amal","family":"Osman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mostafa","family":"Mansour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashraf M.","family":"Bakr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"6952_CR1","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1159\/000540511","volume":"10","author":"S Zhu","year":"2024","unstructured":"Zhu S, Zhang J, Gao L, Ye Q, Mao J (2024) The pathogenesis of nephrotic syndrome: a perspective from B cells. Kidney Dis (Basel) 10:531\u2013544. https:\/\/doi.org\/10.1159\/000540511","journal-title":"Kidney Dis (Basel)"},{"key":"6952_CR2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1167741","volume":"14","author":"F Vincenti","year":"2023","unstructured":"Vincenti F, Angeletti A, Ghiggeri GM (2023) State of the art in childhood nephrotic syndrome: concrete discoveries and unmet needs. Front Immunol 14:1167741. https:\/\/doi.org\/10.3389\/fimmu.2023.1167741","journal-title":"Front Immunol"},{"key":"6952_CR3","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.ekir.2019.09.009","volume":"5","author":"Agrawal S, Merchant ML, Kino J, Li M, Wilkey DW, Gaweda AE, Brier ME, Chanley MA, Gooding JR, Sumner SJ, Klein JB, Smoyer WE; Midwest Pediatric Nephrology Consortium","year":"2019","unstructured":"Agrawal S, Merchant ML, Kino J, Li M, Wilkey DW, Gaweda AE, Brier ME, Chanley MA, Gooding JR, Sumner SJ, Klein JB, Smoyer WE; Midwest Pediatric Nephrology Consortium (2019) Predicting and defining steroid resistance in pediatric nephrotic syndrome using plasma proteomics. Kidney Int Rep 5:66\u201380. https:\/\/doi.org\/10.1016\/j.ekir.2019.09.009","journal-title":"Kidney Int Rep"},{"key":"6952_CR4","doi-asserted-by":"publisher","first-page":"2458","DOI":"10.1016\/j.ekir.2023.08.039","volume":"8","author":"HK Stone","year":"2023","unstructured":"Stone HK, Huang B, Chen C, Ma Q, Bennett MR, Devarajan P (2023) External validation of a urinary biomarker risk score for the prediction of steroid responsiveness in adults with nephrotic syndrome. Kidney Int Rep 8:2458\u20132468. https:\/\/doi.org\/10.1016\/j.ekir.2023.08.039","journal-title":"Kidney Int Rep"},{"key":"6952_CR5","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1146\/annurev-pathmechdis-111523-023509","volume":"20","author":"M Lee","year":"2025","unstructured":"Lee M, Boyce JA, Barrett NA (2025) Cysteinyl leukotrienes in allergic inflammation. Annu Rev Pathol 20:115\u2013141. https:\/\/doi.org\/10.1146\/annurev-pathmechdis-111523-023509","journal-title":"Annu Rev Pathol"},{"key":"6952_CR6","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1097\/MNH.0000000000000381","volume":"27","author":"M Rubinstein","year":"2018","unstructured":"Rubinstein M, Dvash E (2018) Leukotrienes and kidney diseases. Curr Opin Nephrol Hypertens 27:42\u201348. https:\/\/doi.org\/10.1097\/MNH.0000000000000381","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"6952_CR7","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s40620-016-0297-2","volume":"29","author":"MM Zedan","year":"2016","unstructured":"Zedan MM, El-Refaey A, Zaghloul H, Abdelrahim ME, Osman A, Zedan MM, Eltantawy N (2016) Montelukast as an add-on treatment in steroid dependant nephrotic syndrome, randomised-controlled trial. J Nephrol 29:585\u2013592. https:\/\/doi.org\/10.1007\/s40620-016-0297-2","journal-title":"J Nephrol"},{"key":"6952_CR8","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/j.ekir.2022.11.013","volume":"8","author":"J Lai","year":"2022","unstructured":"Lai J, Furgeson S, Bjornstad P, You Z, Tommerdahl KL, Kendrick J (2022) Leukotriene antagonist use is associated with lower systolic blood pressure in adults. Kidney Int Rep 8:373\u2013375. https:\/\/doi.org\/10.1016\/j.ekir.2022.11.013","journal-title":"Kidney Int Rep"},{"key":"6952_CR9","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1055\/s-0040-1718725","volume":"11","author":"L Dawman","year":"2020","unstructured":"Dawman L, Kaur A, Nada R, Chakraborty S, Handa S, Sharawat IK, Tiewsoh K (2020) Autosomal recessive congenital ichthyosis and steroid-resistant nephrotic syndrome due to homozygous mutation in the ALOX12B gene: a novel association with review of literature. J Pediatr Genet 11:28\u201333. https:\/\/doi.org\/10.1055\/s-0040-1718725","journal-title":"J Pediatr Genet"},{"key":"6952_CR10","doi-asserted-by":"publisher","first-page":"92","DOI":"10.3339\/jkspn.2021.25.2.92","volume":"25","author":"JM Lee","year":"2021","unstructured":"Lee JM, Ahn YH, Lim SH, Kang HG (2021) Biomarkers predicting treatment-response in nephrotic syndrome of children: a systematic review. Child Kidney Dis 25:92\u2013111. https:\/\/doi.org\/10.3339\/jkspn.2021.25.2.92","journal-title":"Child Kidney Dis"},{"key":"6952_CR11","doi-asserted-by":"publisher","first-page":"e115216","DOI":"10.1371\/journal.pone.011","volume":"9","author":"CY Chiu","year":"2014","unstructured":"Chiu CY, Tsai MH, Yao TC, Tu YL, Hua MC, Yeh KW, Huang JL (2014) Urinary LTE4 levels as a diagnostic marker for IgE-mediated asthma in preschool children: a birth cohort study. PLoS One 9:e115216. https:\/\/doi.org\/10.1371\/journal.pone.011","journal-title":"PLoS ONE"},{"issue":"4S","key":"6952_CR12","doi-asserted-by":"publisher","first-page":"S1","DOI":"10.1016\/j.kint.2021.05.021","volume":"100","author":"Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group","year":"2021","unstructured":"Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group (2021) Kdigo 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int 100(4S):S1\u2013S276. https:\/\/doi.org\/10.1016\/j.kint.2021.05.021","journal-title":"Kidney Int"},{"key":"6952_CR13","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/s0091-6749(05)80068-5","volume":"86","author":"PJ Manning","year":"1990","unstructured":"Manning PJ, Rokach J, Malo JL, Ethier D, Cartier A, Girard Y, Charleson S, O\u2019Byrne PM (1990) Urinary leukotriene E4 levels during early and late asthmatic responses. J Allergy Clin Immunol 86:211\u2013220. https:\/\/doi.org\/10.1016\/s0091-6749(05)80068-5","journal-title":"J Allergy Clin Immunol"},{"issue":"6","key":"6952_CR14","first-page":"625","volume":"28","author":"S Mir","year":"1998","unstructured":"Mir S, H\u00fcseyinov A, Kantar M, Kabasakal C, Cura A, \u00c7oker I (1998) The role of leukotrienes in the pathogenesis of steroid-sensitive nephrotic syndrome. Turk J Med Sci 28:625\u2013629","journal-title":"Turk J Med Sci"},{"key":"6952_CR15","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1007\/s00467-021-05401-4","volume":"37","author":"T Horinouchi","year":"2022","unstructured":"Horinouchi T, Nozu K, Iijima K (2022) An updated view of the pathogenesis of steroid-sensitive nephrotic syndrome. Pediatr Nephrol 37:1957\u20131965. https:\/\/doi.org\/10.1007\/s00467-021-05401-4","journal-title":"Pediatr Nephrol"},{"key":"6952_CR16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0312232","volume":"20","author":"CJ May","year":"2025","unstructured":"May CJ, Ford NP, Welsh GI, Saleem MA (2025) Biomarkers to predict or measure steroid resistance in idiopathic nephrotic syndrome: a systematic review. PLoS One 20:e0312232. https:\/\/doi.org\/10.1371\/journal.pone.0312232","journal-title":"PLoS One"},{"key":"6952_CR17","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/BF00862515","volume":"4","author":"Y Kikawa","year":"1990","unstructured":"Kikawa Y, Nakai A, Shigematsu Y, Sudo M, Kato K, Haruki S (1990) Leukotriene B4 production in children with steroid-responsive nephrotic syndrome. Pediatr Nephrol 4:343\u2013344. https:\/\/doi.org\/10.1007\/BF00862515","journal-title":"Pediatr Nephrol"},{"key":"6952_CR18","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1007\/s00467-003-1399-3","volume":"19","author":"A Bakr","year":"2004","unstructured":"Bakr A, Hawas S, Slem S, Moniem AA, Ghatab T, Tawfik M (2004) 5-lipoxygenase and leukotriene A4 hydrolase expression in primary nephrotic syndrome. Pediatr Nephrol 19:396\u2013399. https:\/\/doi.org\/10.1007\/s00467-003-1399-3","journal-title":"Pediatr Nephrol"}],"container-title":["Pediatric Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00467-025-06952-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00467-025-06952-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00467-025-06952-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T08:39:53Z","timestamp":1765528793000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00467-025-06952-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,30]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["6952"],"URL":"https:\/\/doi.org\/10.1007\/s00467-025-06952-6","relation":{},"ISSN":["0931-041X","1432-198X"],"issn-type":[{"type":"print","value":"0931-041X"},{"type":"electronic","value":"1432-198X"}],"subject":[],"published":{"date-parts":[[2025,9,30]]},"assertion":[{"value":"3 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 August 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the Institutional Research Board of the Faculty of Medicine, Mansoura University (Date: 19\u20137-2020, Code number: MS.20.07.1197). Informed consent was obtained from the parents of all study participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}