Pediatric Severe Lupus Nephritis Detected by School Urinary Screening: A Case Report

Pediatric Severe Lupus Nephritis Detected by School Urinary Screening: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Pediatric Severe Lupus Nephritis Detected by School Urinary Screening: A Case Report Daisuke Fujimori, Hiroki Yokoyama, Ryo Kinoshita, Mayumi Sakaguchi, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7598411/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 14 You are reading this latest preprint version Abstract Pediatric lupus nephritis (LN) often presents with severe histopathological features at diagnosis, frequently resulting in poor renal outcomes. Early detection remains challenging, particularly in cases presenting only urinary abnormalities. Herein, we report the case of a 15-year-old female diagnosed with class IV LN, initially identified through school urinary screening owing to the hematuria and proteinuria findings. Apart from elevated blood pressure and asymptomatic oral mucosal lesions, she displayed no other notable clinical signs or symptoms. Laboratory tests revealed hypocomplementemia, leukopenia, and the presence of autoantibodies. Class IV LN diagnosis was confirmed by findings consistent with full-house nephropathy and diffuse proliferative nephritis, by the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification criteria. Following 6 months of treatment with methylprednisolone pulse therapy, mycophenolate mofetil, hydroxychloroquine, and candesartan, the patient achieved complete renal remission. This case highlights the potential value of school urinary screening in the early detection and management of pediatric LN. systemic lupus erythematosus lupus nephritis screening early detection Figures Figure 1 Figure 2 Introduction Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE), often more severe in children than adults [ 1 ]. It occurs in 50%–70% of pediatric SLE cases, especially among Asian populations [ 2 – 4 ]. The International Society of Nephrology/Renal Pathology Society (ISN/RPS) classifies LN, with classes III and IV being the most severe, and most pediatric cases presenting at these stages [ 3 , 5 ]. Despite improvements in SLE management, renal outcomes remain poor, with up to 15% progressing to stage 5 chronic kidney disease (CKD) [ 6 ]. Early diagnosis and treatment are crucial to improve prognosis. Renal involvement is frequently observed at SLE onset; however, early detection can be challenging without subjective symptoms [ 3 , 7 ]. In Japan and certain other Asian regions, school urinary screening programs facilitate the early identification of chronic nephritis, which may aid in the diagnosis of LN [ 8 – 10 ]. However, reports of severe LN cases identified solely through school urinary screening remain limited. Herein, we present a case of severe pediatric LN diagnosed via school urinary screening in patient who was asymptomatic. Case Report The patient was a 15-year-old girl who had a history of short stature and mental retardation. Two months before the visit, hematuria and proteinuria were noted for the first time during primary and secondary school urinary screening. During a tertiary follow-up examination by a primary doctor, she was noted to have worsening proteinuria with hypocomplementemia and cytopenia, but she had no subjective symptoms. Subsequently, the patient was referred to our hospital. She had no family history of rheumatic disease. She was 142.1 cm (− 2.7 SD) tall and weighed 50.5 kg, with a body temperature of 37.2°C and blood pressure of 126/67 mmHg. There was no photosensitivity or skin rash, but there was a painless rash on the mucous membrane of the hard palate. There was no arthritis, neurologic abnormalities, or edema. Laboratory tests revealed leukopenia (2,500/µL) and anemia (8.8 g/dL), along with hypocomplementemia (C3: 39.6 mg/dL; C4: 3.2 mg/dL; CH50: 11.7 U/mL). In addition, several antibodies were positive as follows: antinuclear antibodies (ANA), 1:640; anti-double-stranded DNA antibodies, 331.5 U/mL (ELISA; normal, < 12 U/mL); and anti-cardiolipin antibodies, 16.5 U/mL (ELISA; normal, 100/HPF, white blood cells 50–99/HPF, and cellular casts 1–4/HPF. Other examinations, including cranial magnetic resonance imaging, contrast computed tomography of the neck to pelvis, ophthalmologic examination, echocardiography, electrocardiography, and pulmonary function test, revealed no organ involvement other than the kidneys. Renal biopsy revealed that almost all glomeruli had active lesions, including endocapillary proliferation, nuclear decay, and wire loop lesions, on pathology examination (Fig. 1 a,b). There were no chronic lesions. Fluorescent antibody analysis showed granular IgG, IgA, IgM, C3, C4, C1q deposition in the capillary wall and mesangium; the so-called “full-house pattern.” Electron microscopy revealed numerous subendothelial deposits (Fig. 1 c). Based on these findings, the patient was diagnosed as class IV LN, according to the ISN/RPS classification, with a severe SLE Disease Activity Index (SLEDAI) score of 23. Subsequently, she underwent two courses of steroid pulse therapy, followed by oral prednisolone, mycophenolate mofetil, and hydroxychloroquine. Candesartan was concomitantly administered for renal protection. Thereafter, the cytopenia and hypocomplementemia rapidly normalized. The proteinuria temporarily worsened to the nephrotic range after steroid pulse therapy but gradually improved thereafter. After 6 months of treatment, the urinary protein level decreased to 0.18 g/gCr, with no obvious deterioration of renal function. Discussion This case highlights a patient with severe LN identified solely through urinary abnormalities detected during school screening, which allowed for early intervention and a favorable clinical outcome. Diagnosing LN in individuals who are asymptomatic is challenging and often depends on urinary screening or incidental findings. Outside select Asian regions (e.g., Japan, South Korea, and Taiwan), screening opportunities are limited owing to the absence of standardized nationwide programs, leaving the prevalence of undiagnosed LN uncertain. Lupus nephritis frequently presents at the onset of SLE and is associated with poor renal outcomes. A study in Korea found that LN cases diagnosed at the onset of SLE are more likely to exhibit class IV pathology and complications such as acute kidney injury and end-stage renal disease (ESRD), compared with early-onset LN developing within 5 year of SLE diagnosis [ 11 ]. This finding underscores the importance of early treatment in cases presenting urinary abnormalities as a part of initial symptoms, since these are at higher risk for poor renal outcomes. Japan's school urinary screening program, introduced in 1974, may assist in the early identification of LN [ 8 ]. A typical school urinary screening program follows a four-stage process, with students progressing through subsequent stages if each result indicates abnormalities (Fig. 2 ). The first two stages, conducted at school, use urine test strips to detect proteinuria and hematuria. In the tertiary stage, a primary care physician conducts detailed urinalysis (including sediment examination, UP/Cr, and β2-microglobulin-to-creatinine ratio) and blood tests (albumin, creatinine, and complement C3 levels). In our region, complete blood counts are also recommended. The final diagnostic evaluation is typically conducted by a pediatric nephrologist. Herein, the findings of proteinuria, hematuria, hypocomplementemia, and cytopenia raised suspicion for SLE. The cost-effectiveness of school urinary screening is debated globally owing to the high false-positive rates and low CKD detection rates [ 12 ]. However, in Japan, the high incidence of IgA nephropathy and lower screening costs have demonstrated economic benefits. For example, screening has been shown to reduce the IgA nephropathy-related ESRD rates and improve cost-effectiveness [ 13 ]. Although the impact of Japan's screening program on LN remains unclear, studies from Taiwan suggest a positive effect, with improved LN prognosis and fewer cases progressing to dialysis [ 9 ]. In Taiwan, LN accounted for 31.6% of students with abnormal urinalysis findings, making it the most common cause of glomerulonephritis [ 9 ]. By contrast, Matsumura et al found LN in only 3 of 9,544 positive cases during tertiary school urinary screening in Chiba City from 1975 to 2011 [ 14 ]. In South Korea, LN accounted for 0.5% of students with positive urine samples [ 10 ]. The reason for the different LN detection rates among Asian countries is unclear, but it is interesting to note that antinuclear antibodies (ANAs) were included during the tertiary screening in Taiwan. Most LN cases in Taiwan initially did not meet the full criteria for SLE, despite being positive for ANA; symptoms developed gradually, indicating that screening may capture early-stage disease. Given the high rates of LN in non-Caucasian populations, school urinary screening programs could hold considerable promise in Asia [ 15 ]. This study highlights the potential of school urinary screening for the early detection and treatment of LN in cases presenting with urinary abnormalities alone. However, identifying novel biomarkers for silent LN remains crucial for advancing early diagnosis and improving outcomes. Declarations Acknowledgements We thank the family of the patient for their cooperation and contribution to this study. Funding This study did not receive financial support from any funding agency. Ethics approval The Ethical review board, Faculty of Medicine Tottori University waived the need of formal ethical approval for this study. Informed consent was obtained from the patient’s mother for publication of this case report and any accompanying images. Author contributions D. Fujimori drafted the initial manuscript and approved the final manuscript as submitted. R. Kinoshita, M. Sakaguchi, and Y. Yamada treated and diagnosed the patient. T. Horie contributed to the acquisition of electron microscopy images and the interpretation of the pathological findings. H. Yokohama and N. Namba interpreted the patient data and critically revised the manuscript. Data a vailability s tatement All datasets generated for this study are included in the article/supplementary material. Material and/or code availability Not applicable. Compliance with Ethical Standards Competing interests The authors have no conflicts of interest to declare that are relevant to the content of this article. Research involving h uman p articipants All procedures performed in this study involving the human participant were in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from the parents of the participants in this study. Clinical trial number Not applicable. References Ambrose N, Morgan TA, Galloway J, Ionnoau Y, Beresford MW, Isenberg DA, et al. Differences in disease phenotype and severity in SLE across age groups. Lupus. 2016 Dec;25(14):1542-50. Cann MP, Sage AM, McKinnon E, Lee SJ, Tunbridge D, Larkins NG, et al. Childhood systemic lupus erythematosus: presentation, management and long-term outcomes in an Australian cohort. Lupus. 2022 Feb;31(2):246-55. Lee PY, Yeh KW, Yao TC, Lee WI, Lin YJ, Huang JL. The outcome of patients with renal involvement in pediatric-onset systemic lupus erythematosus—a 20-year experience in Asia. Lupus. 2013 Dec;22(14):1534-40. Levy DM, Peschken CA, Tucker LB, Chédeville G, Huber AM, Pope JE, et al. Influence of ethnicity on childhood-onset systemic lupus erythematosus: results from a multiethnic multicenter Canadian cohort. Arthritis Care Res (Hoboken). 2013 Jan;65(1):152-60. Bajema IM, Wilhelmus S, Alpers CE, Bruijn JA, Colvin RB, Cook HT, et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int. 2018 Apr;93(4):789-96. Oni L, Wright RD, Marks S, Beresford MW, Tullus K. Kidney outcomes for children with lupus nephritis. Pediatr Nephrol. 2021 Jun;36(6):1377-85. Sassi RH, Hendler JV, Piccoli GF, Gasparin AA, da Silva Chakr RM, Brenol JC, et al. Age of onset influences on clinical and laboratory profile of patients with systemic lupus erythematosus. Clin Rheumatol. 2017 Jan;36(1):89-95. Murakami M, Yamamoto H, Ueda Y, Murakami K, Yamauchi K. Urinary screening of elementary and junior high-school children over a 13-year period in Tokyo. Pediatr Nephrol. 1991 Jan;5(1):50-3. Lin CY, Hsieh CC, Chen WP, Yang LY, Wang HH. The underlying diseases and follow-up in Taiwanese children screened by urinalysis. Pediatr Nephrol. 2001 Mar;16(3):232-7. Cho BS, Kim SD. School urinalysis screening in Korea. Nephrology. 2007 Dec;12 Suppl 3:S3-7. Kwon OC, Park JH, Lee SW, Song JJ, Park YB, Park MC. Worse renal presentation and prognosis in initial-onset lupus nephritis than early-onset lupus nephritis. Yonsei Med J. 2020;61(11):951. Hogg RJ. Screening for CKD in children: a global controversy. Clin J Am Soc Nephrol. 2009 Feb;4(2):509-15. Honda K, Akune Y, Goto R. Cost-effectiveness of school urinary screening for early detection of IgA nephropathy in Japan. JAMA Netw Open. 2024 Feb 5;7(2):e2356412. Matsumura C. School urinary screening in Chiba City. [Chiba-shi Gakkou kennyou]. Jpn J Pediatr. 2013;66:623-9. [in Japanese]. Miguel DF, Terreri MT, Pereira RMR, Bonfá E, Silva CAA, Corrente JE, et al. Comparison of urinary parameters, biomarkers, and outcome of childhood systemic lupus erythematosus early onset-lupus nephritis. Adv Rheumatol. 2020 Feb 1;60(1):10. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 04 Dec, 2025 Reviews received at journal 18 Oct, 2025 Reviews received at journal 11 Oct, 2025 Reviewers agreed at journal 11 Oct, 2025 Reviewers agreed at journal 11 Oct, 2025 Reviews received at journal 10 Oct, 2025 Reviews received at journal 05 Oct, 2025 Reviewers agreed at journal 05 Oct, 2025 Reviewers agreed at journal 05 Oct, 2025 Reviewers invited by journal 29 Sep, 2025 Editor assigned by journal 29 Sep, 2025 Editor invited by journal 21 Sep, 2025 Submission checks completed at journal 19 Sep, 2025 First submitted to journal 19 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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1","display":"","copyAsset":false,"role":"figure","size":25741139,"visible":true,"origin":"","legend":"\u003cp\u003ePathological findings of renal biopsy\u003c/p\u003e\n\u003cp\u003eOn light microscopy, the glomerulus shows (a) global moderate mesangial proliferation with endocapillary hypercellularity, wire loop lesions, and mild extracapillary cellular proliferation (black arrow) and (b) segmentally thickened basement membrane (PAS stain, 200×). (c) Transmission electron microscopy shows abundant electron-dense deposits in the subendothelium, with some deposited in the mesangial region. The basement membrane is thickened and forms a wire loop lesion (2,500×)\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-7598411/v1/b7fa8fa104c61a783bdf62aa.png"},{"id":93336631,"identity":"0825da80-5283-4857-8c6b-cca3391968f8","added_by":"auto","created_at":"2025-10-12 14:06:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":921502,"visible":true,"origin":"","legend":"\u003cp\u003eExample of a school urinary screening test in Japan\u003c/p\u003e\n\u003cp\u003eUrine specimens are collected at home in the early morning. The first urine sample is tested for proteinuria and occult blood using a urine dipstick. Students who test positive undergo a second urine test. The results of both tests are evaluated by the school board. Those with persistent abnormalities are referred to a primary care doctor for a third, more detailed examination, which includes a physical examination, urinalysis, and blood tests such as albumin, creatinine, and C3. Finally, a pediatric kidney disease specialist conducts a fourth detailed examination\u003c/p\u003e","description":"","filename":"Fig22.png","url":"https://assets-eu.researchsquare.com/files/rs-7598411/v1/be36d6e75f4fc1e280e50782.png"},{"id":93337977,"identity":"28364a53-f334-4c62-96bc-dc5234b5f59e","added_by":"auto","created_at":"2025-10-12 14:15:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":44362739,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7598411/v1/be99efee-7e4d-4b7d-ac1a-be4971c293c8.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pediatric Severe Lupus Nephritis Detected by School Urinary Screening: A Case Report","fulltext":[{"header":"Introduction","content":"\u003cp\u003eLupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE), often more severe in children than adults [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It occurs in 50%\u0026ndash;70% of pediatric SLE cases, especially among Asian populations [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The International Society of Nephrology/Renal Pathology Society (ISN/RPS) classifies LN, with classes III and IV being the most severe, and most pediatric cases presenting at these stages [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Despite improvements in SLE management, renal outcomes remain poor, with up to 15% progressing to stage 5 chronic kidney disease (CKD) [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Early diagnosis and treatment are crucial to improve prognosis.\u003c/p\u003e\u003cp\u003eRenal involvement is frequently observed at SLE onset; however, early detection can be challenging without subjective symptoms [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In Japan and certain other Asian regions, school urinary screening programs facilitate the early identification of chronic nephritis, which may aid in the diagnosis of LN [\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, reports of severe LN cases identified solely through school urinary screening remain limited. Herein, we present a case of severe pediatric LN diagnosed via school urinary screening in patient who was asymptomatic.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eThe patient was a 15-year-old girl who had a history of short stature and mental retardation. Two months before the visit, hematuria and proteinuria were noted for the first time during primary and secondary school urinary screening. During a tertiary follow-up examination by a primary doctor, she was noted to have worsening proteinuria with hypocomplementemia and cytopenia, but she had no subjective symptoms. Subsequently, the patient was referred to our hospital. She had no family history of rheumatic disease. She was 142.1 cm (\u0026minus;\u0026thinsp;2.7 SD) tall and weighed 50.5 kg, with a body temperature of 37.2\u0026deg;C and blood pressure of 126/67 mmHg. There was no photosensitivity or skin rash, but there was a painless rash on the mucous membrane of the hard palate. There was no arthritis, neurologic abnormalities, or edema.\u003c/p\u003e\u003cp\u003eLaboratory tests revealed leukopenia (2,500/\u0026micro;L) and anemia (8.8 g/dL), along with hypocomplementemia (C3: 39.6 mg/dL; C4: 3.2 mg/dL; CH50: 11.7 U/mL). In addition, several antibodies were positive as follows: antinuclear antibodies (ANA), 1:640; anti-double-stranded DNA antibodies, 331.5 U/mL (ELISA; normal, \u0026lt;\u0026thinsp;12 U/mL); and anti-cardiolipin antibodies, 16.5 U/mL (ELISA; normal, \u0026lt;\u0026thinsp;12.3 U/mL). The direct Coombs test was positive. Urinalysis showed a urinary protein/creatinine ratio (UP/Cr) of 4.52 g/gCr, red blood cells\u0026thinsp;\u0026gt;\u0026thinsp;100/HPF, white blood cells 50\u0026ndash;99/HPF, and cellular casts 1\u0026ndash;4/HPF. Other examinations, including cranial magnetic resonance imaging, contrast computed tomography of the neck to pelvis, ophthalmologic examination, echocardiography, electrocardiography, and pulmonary function test, revealed no organ involvement other than the kidneys.\u003c/p\u003e\u003cp\u003eRenal biopsy revealed that almost all glomeruli had active lesions, including endocapillary proliferation, nuclear decay, and wire loop lesions, on pathology examination (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ea,b). There were no chronic lesions. Fluorescent antibody analysis showed granular IgG, IgA, IgM, C3, C4, C1q deposition in the capillary wall and mesangium; the so-called \u0026ldquo;full-house pattern.\u0026rdquo; Electron microscopy revealed numerous subendothelial deposits (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003ec). Based on these findings, the patient was diagnosed as class IV LN, according to the ISN/RPS classification, with a severe SLE Disease Activity Index (SLEDAI) score of 23.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eSubsequently, she underwent two courses of steroid pulse therapy, followed by oral prednisolone, mycophenolate mofetil, and hydroxychloroquine. Candesartan was concomitantly administered for renal protection. Thereafter, the cytopenia and hypocomplementemia rapidly normalized. The proteinuria temporarily worsened to the nephrotic range after steroid pulse therapy but gradually improved thereafter. After 6 months of treatment, the urinary protein level decreased to 0.18 g/gCr, with no obvious deterioration of renal function.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case highlights a patient with severe LN identified solely through urinary abnormalities detected during school screening, which allowed for early intervention and a favorable clinical outcome. Diagnosing LN in individuals who are asymptomatic is challenging and often depends on urinary screening or incidental findings. Outside select Asian regions (e.g., Japan, South Korea, and Taiwan), screening opportunities are limited owing to the absence of standardized nationwide programs, leaving the prevalence of undiagnosed LN uncertain.\u003c/p\u003e\u003cp\u003eLupus nephritis frequently presents at the onset of SLE and is associated with poor renal outcomes. A study in Korea found that LN cases diagnosed at the onset of SLE are more likely to exhibit class IV pathology and complications such as acute kidney injury and end-stage renal disease (ESRD), compared with early-onset LN developing within 5\u0026nbsp;year of SLE diagnosis [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis finding underscores the importance of early treatment in cases presenting urinary abnormalities as a part of initial symptoms, since these are at higher risk for poor renal outcomes.\u003c/p\u003e\u003cp\u003eJapan's school urinary screening program, introduced in 1974, may assist in the early identification of LN [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. A typical school urinary screening program follows a four-stage process, with students progressing through subsequent stages if each result indicates abnormalities (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The first two stages, conducted at school, use urine test strips to detect proteinuria and hematuria. In the tertiary stage, a primary care physician conducts detailed urinalysis (including sediment examination, UP/Cr, and β2-microglobulin-to-creatinine ratio) and blood tests (albumin, creatinine, and complement C3 levels). In our region, complete blood counts are also recommended. The final diagnostic evaluation is typically conducted by a pediatric nephrologist. Herein, the findings of proteinuria, hematuria, hypocomplementemia, and cytopenia raised suspicion for SLE.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe cost-effectiveness of school urinary screening is debated globally owing to the high false-positive rates and low CKD detection rates [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. However, in Japan, the high incidence of IgA nephropathy and lower screening costs have demonstrated economic benefits. For example, screening has been shown to reduce the IgA nephropathy-related ESRD rates and improve cost-effectiveness [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Although the impact of Japan's screening program on LN remains unclear, studies from Taiwan suggest a positive effect, with improved LN prognosis and fewer cases progressing to dialysis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn Taiwan, LN accounted for 31.6% of students with abnormal urinalysis findings, making it the most common cause of glomerulonephritis [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. By contrast, Matsumura et al found LN in only 3 of 9,544 positive cases during tertiary school urinary screening in Chiba City from 1975 to 2011 [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In South Korea, LN accounted for 0.5% of students with positive urine samples [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The reason for the different LN detection rates among Asian countries is unclear, but it is interesting to note that antinuclear antibodies (ANAs) were included during the tertiary screening in Taiwan. Most LN cases in Taiwan initially did not meet the full criteria for SLE, despite being positive for ANA; symptoms developed gradually, indicating that screening may capture early-stage disease. Given the high rates of LN in non-Caucasian populations, school urinary screening programs could hold considerable promise in Asia [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis study highlights the potential of school urinary screening for the early detection and treatment of LN in cases presenting with urinary abnormalities alone. However, identifying novel biomarkers for silent LN remains crucial for advancing early diagnosis and improving outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the family of the patient for their cooperation and contribution to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study did not receive financial support from any funding agency.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe Ethical review board, Faculty of Medicine Tottori University waived the need of formal ethical approval for this study. Informed consent was obtained from the patient\u0026rsquo;s mother for publication of this case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eD. Fujimori drafted the initial manuscript and approved the final manuscript as submitted. R. Kinoshita, M. Sakaguchi, and Y. Yamada treated and diagnosed the patient.\u0026nbsp;T. Horie contributed to the acquisition of electron microscopy images and the interpretation of the pathological findings. H.\u0026nbsp;Yokohama and N. Namba interpreted the patient data and critically revised the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ea\u003c/strong\u003e\u003cstrong\u003evailability\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003es\u003c/strong\u003e\u003cstrong\u003etatement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll datasets generated for this study are included in the article/supplementary material.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterial and/or code availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompliance with Ethical Standards\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The authors have no\u0026nbsp;conflicts of interest\u0026nbsp;to declare that are relevant to the content of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResearch involving\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eh\u003c/strong\u003e\u003cstrong\u003euman\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003ep\u003c/strong\u003e\u003cstrong\u003earticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll procedures performed in this study involving the human participant were in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInformed consent was obtained from the parents of the participants in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003cstrong\u003e\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAmbrose N, Morgan TA, Galloway J, Ionnoau Y, Beresford MW, Isenberg DA, et al. Differences in disease phenotype and severity in SLE across age groups. Lupus. 2016 Dec;25(14):1542-50.\u003c/li\u003e\n\u003cli\u003eCann MP, Sage AM, McKinnon E, Lee SJ, Tunbridge D, Larkins NG, et al. Childhood systemic lupus erythematosus: presentation, management and long-term outcomes in an Australian cohort. Lupus. 2022 Feb;31(2):246-55.\u003c/li\u003e\n\u003cli\u003eLee PY, Yeh KW, Yao TC, Lee WI, Lin YJ, Huang JL. The outcome of patients with renal involvement in pediatric-onset systemic lupus erythematosus\u0026mdash;a 20-year experience in Asia. Lupus. 2013 Dec;22(14):1534-40.\u003c/li\u003e\n\u003cli\u003eLevy DM, Peschken CA, Tucker LB, Ch\u0026eacute;deville G, Huber AM, Pope JE, et al. Influence of ethnicity on childhood-onset systemic lupus erythematosus: results from a multiethnic multicenter Canadian cohort. Arthritis Care Res (Hoboken). 2013 Jan;65(1):152-60.\u003c/li\u003e\n\u003cli\u003eBajema IM, Wilhelmus S, Alpers CE, Bruijn JA, Colvin RB, Cook HT, et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int. 2018 Apr;93(4):789-96.\u003c/li\u003e\n\u003cli\u003eOni L, Wright RD, Marks S, Beresford MW, Tullus K. Kidney outcomes for children with lupus nephritis. Pediatr Nephrol. 2021 Jun;36(6):1377-85.\u003c/li\u003e\n\u003cli\u003eSassi RH, Hendler JV, Piccoli GF, Gasparin AA, da Silva Chakr RM, Brenol JC, et al. Age of onset influences on clinical and laboratory profile of patients with systemic lupus erythematosus. Clin Rheumatol. 2017 Jan;36(1):89-95.\u003c/li\u003e\n\u003cli\u003eMurakami M, Yamamoto H, Ueda Y, Murakami K, Yamauchi K. Urinary screening of elementary and junior high-school children over a 13-year period in Tokyo. Pediatr Nephrol. 1991 Jan;5(1):50-3.\u003c/li\u003e\n\u003cli\u003eLin CY, Hsieh CC, Chen WP, Yang LY, Wang HH. The underlying diseases and follow-up in Taiwanese children screened by urinalysis. Pediatr Nephrol. 2001 Mar;16(3):232-7.\u003c/li\u003e\n\u003cli\u003eCho BS, Kim SD. School urinalysis screening in Korea. Nephrology. 2007 Dec;12 Suppl 3:S3-7.\u003c/li\u003e\n\u003cli\u003eKwon OC, Park JH, Lee SW, Song JJ, Park YB, Park MC. Worse renal presentation and prognosis in initial-onset lupus nephritis than early-onset lupus nephritis. Yonsei Med J. 2020;61(11):951.\u003c/li\u003e\n\u003cli\u003eHogg RJ. Screening for CKD in children: a global controversy. Clin J Am Soc Nephrol. 2009 Feb;4(2):509-15.\u003c/li\u003e\n\u003cli\u003eHonda K, Akune Y, Goto R. Cost-effectiveness of school urinary screening for early detection of IgA nephropathy in Japan. JAMA Netw Open. 2024 Feb 5;7(2):e2356412.\u003c/li\u003e\n\u003cli\u003eMatsumura C. School urinary screening in Chiba City. [Chiba-shi Gakkou kennyou]. Jpn J Pediatr. 2013;66:623-9. [in Japanese].\u003c/li\u003e\n\u003cli\u003eMiguel DF, Terreri MT, Pereira RMR, Bonf\u0026aacute; E, Silva CAA, Corrente JE, et al. Comparison of urinary parameters, biomarkers, and outcome of childhood systemic lupus erythematosus early onset-lupus nephritis. Adv Rheumatol. 2020 Feb 1;60(1):10.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"systemic lupus erythematosus, lupus nephritis, screening, early detection","lastPublishedDoi":"10.21203/rs.3.rs-7598411/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7598411/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003ePediatric lupus nephritis (LN) often presents with severe histopathological features at diagnosis, frequently resulting in poor renal outcomes. Early detection remains challenging, particularly in cases presenting only urinary abnormalities. Herein, we report the case of a 15-year-old female diagnosed with class IV LN, initially identified through school urinary screening owing to the hematuria and proteinuria findings. Apart from elevated blood pressure and asymptomatic oral mucosal lesions, she displayed no other notable clinical signs or symptoms. Laboratory tests revealed hypocomplementemia, leukopenia, and the presence of autoantibodies. Class IV LN diagnosis was confirmed by findings consistent with full-house nephropathy and diffuse proliferative nephritis, by the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification criteria. Following 6 months of treatment with methylprednisolone pulse therapy, mycophenolate mofetil, hydroxychloroquine, and candesartan, the patient achieved complete renal remission. This case highlights the potential value of school urinary screening in the early detection and management of pediatric LN.\u003c/p\u003e","manuscriptTitle":"Pediatric Severe Lupus Nephritis Detected by School Urinary Screening: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-12 14:06:38","doi":"10.21203/rs.3.rs-7598411/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-04T18:09:53+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-18T04:22:15+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-11T23:06:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"108828468240218166944405449242289192354","date":"2025-10-11T22:10:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"52648666470575047045483382810850797931","date":"2025-10-11T15:24:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-11T01:12:39+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-05T13:25:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"300862035402839924993429170137542765495","date":"2025-10-05T08:53:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"54162431260246661989729953226141294972","date":"2025-10-05T08:12:50+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-29T08:43:39+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-29T08:38:32+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-21T13:11:22+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-19T11:08:48+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Medicine","date":"2025-09-19T11:05:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c77b9296-891b-4b5e-bafe-3745a3d03bc2","owner":[],"postedDate":"October 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-03-31T06:57:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-12 14:06:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7598411","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7598411","identity":"rs-7598411","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}