Reference Range for Urine Red Blood Cell-to-Creatinine Ratio in Japanese Children

Reference Range for Urine Red Blood Cell-to-Creatinine Ratio in Japanese Children | 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 Research Article Reference Range for Urine Red Blood Cell-to-Creatinine Ratio in Japanese Children Hiroki Matsubayashi, Naoya Fujita, Katsuaki Kasahara, Osamu Uemura This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8625088/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Hematuria is important parameter for diagnosis of kidney disease and assessing treatment efficacy. However, reference values for the urine RBC-to-creatinine ratio (urine RBC/Cre), caluculated by dividing urine creatinine for correcting urine concentration, are not provided. Methods We retrospectively analyzed urine RBC counts and urine Cre values in children aged 18 years or younger from four facilities between February 2016 and December 2024. From these, we calculated the urine RBC/Cre using the formula: urine RBC [/µL] / urine Cre [mg/dL] × 10 5 . The calculated urine RBC/Cre results were expressed in units of [×10 5 /mgCre]. We established detailed reference values (the median, 2.5th percentile, and 97.5th percentile) for this urine RBC/Cre by sex and age group. Results Based on the aggregated urine RBC/Cre of 280 participants, we established detailed reference values by age and sex. The overall median urine RBC/Cre was 3.7 [×10 5 /mgCre]. The median value was 3.8 for boys and 3.5 for girls. Age-specific median values in boys vs. girls were 8.2 vs. 9.2 for ages 0–5 years, 2.7 vs. 4.0 for ages 6–11 years, and 1.1 vs. 1.7 for ages 12–17 years. Age-specific 97.5th percentile values in boys vs. girls were 175.5 vs. 95.0 for ages 0–5 years, 35.5 vs. 19.3 for ages 6–11 years, and 5.8 vs. 20.0 for ages 12–17 years. Conclusion This study provides the first reference values for urine RBC/Cre in children. This may facilitate more reliable interpretation of urinary findings in pediatric clinical practice. Figures Figure 1 Figure 2 Introduction Urinalysis is essential in the diagnosis and management of kidney disease. Hematuria is as important parameter as proteinuria in screening tests, diagnosis of kidney disease, and assessing treatment efficacy. For the diagnosis of hematuria, the dipstick test for hematuria and the visual examination of red blood cell counts in urine sediment have been commonly used. However, this method had the drawbacks of being dependent on the skill of the examiner and for not accounting for the degree of urine concentration [ 1 ]. Urine flow cytometry (urine FCM), a method for testing formed elements in urine, has been increasingly used in various medical institutions in recent years. This method is performed automatically using urine FCM testing equipment, which is considered to eliminate the bias associated with the skill of the examiner [ 1 ]. However, urine FCM measurement values also do not account for urine concentration and may not provide accurate evaluations. The urine protein-to-creatinine ratio, calculated by dividing urine protein values by urine creatinine (urine Cre), has been reported to correlate with urine protein values obtained through 24-hour urine collection and is widely used for evaluating proteinuria as it can correct for urine concentration [ 2 , 3 ]. However, the red blood cell count obtained by the urine sediment visual inspection method is not continuous value, making it impossible to calculate the urine Cre ratio. Given this background, we hypothesized that a urine RBC/Cre – calculated by dividing a continuously measured urine RBC counts from FCM by the urine Cre – would allow a more accurate assessment of hematuria independent of examiner skill or urine concentration. To date, no reference values for urine RBC/Cre in children have been reported, underscoring the need for this study. The objective of this study is to establish reference values for urine RBC/Cre based on past urine test results from subjects considered to have no underlying renal disease causing hematuria. Materials and methods In this retrospective study, we reviewed the medical records of pediatric participants aged 18 years or younger who underwent urinalysis at each Seirei Hamamatsu General Hospital, Aichi Children’s Health and Medical Center, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital or Hamamatsu University Hospital between February 2016 and December 2024, and diagnosed with monosymptomatic enuresis, mild hydronephrosis, orthostatic proteinuria, or short stature. The definitions of each diseases are as follows: monosymptomatic enuresis Intermittent urinary incontinence during sleep in children aged 5 years or older, without daytime urinary incontinence or other lower urinary tract symptoms mild hydronephrosis Defined grade 1 by the Society for Fetal Urology classification (SFU) and no hydroureter orthostatic proteinuria The presence of protein in urine during upright posture but not when supine We diagnosed orthostatic proteinuria based on the normal morning urine on a 3-point urine collection method, or normal urine before a forward-bending test short stature Limited to familial short stature or constitutional short stature The exclusion criteria were as follows: (1) patients with a history of hematuria; (2) patients with a diagnosis that may affect urine finding in medical records; (3) patients with congenital anomalies of the kidney and urinary tract (CAKUT) excluding SFU grade 1 hydronephrosis; (4) patients for whom urine FCM and urine Cre test were not performed on the same specimen; (5) patients who were menstruating at the time of urine test; (6) patients considered inappropriate for analysis by the attending physician; (7) patients who refused to participate in this study. We obtained the following data from medical records retrospectively: date of birth, sex, diagnosis, date of the urine sample was collected, data of urine test using urine FCM, type of the fully automatic urinary particle analyzer, method of urine Cre measurement (enzyme method or Jaffe method), urine sediment, urine RBC (calculated using urine FCM). We used only one urine sample per patient, and it should be the first sample in which urine RBC and urine Cre are measured (morning urine is acceptable). Based on the collected these values, urine RBC was divided by urine Cre to calculate urine RBC/Cre. The urine RBC/Cre was expressed in units of [×10 5 /mgCre]. The reference value for urine RBC/Cre for each age group and sex were calculated from the collected data. Values by age were summarized by age group (0 to 5 years, 6 to 11 years, 12 to 17 years) and sex. We rounded off to the nearest thousandth of the urine RBC/Cre values. The median, 2.5 th percentile, and 97.5 th percentile values were calculated for each age group and sex, and the range between the 2.5 th percentile and 97.5 th percentile values was defined as the reference range. Statistical analyses were performed using EZR (Easy R), which is a graphical user interface for R developed by the Jichi Medical University Saitama Medical Center. Results Table 1 Clinical characteristics of participants and data Total 280 Age 0–5 years 123 (43.9%) 6–11 years 89 (31.8%) 12–17 years 68 (24.2%) Sex Male 162 (57.9%) Female 118 (42.1%) Diagnosis monosymptomatic enuresis 72 (25.7%) mild hydronephrosis 116 (41.4%) orthostatic proteinuria 91 (32.5%) short stature 1 (0.4%) Type of the fully automatic urinary particle analyzer UF-5000 174 (62.1%) UF-1500 99 (35.4%) UF-1000i 7 (2.5%) Method of urine Cre measurement Enzyme method 280 (100%) Jaffe method 0 Data are presented as n (%) A total of 280 children met the inclusion criteria. These participants drawn from the four facilities listed above and comprised 162 boys (57.9%) and 118 girls (42.1%). The age distribution of the cohort was as follows: 123 children (44%) were 0–5 years old, 89 (32%) were 6–11 years old, and 68 (24%) were 12–17 years old. The most common disease was hydronephrosis, with 116 cases. This was followed by orthostatic proteinuria in 91 cases, monosymptomatic enuresis in 72 cases, and short stature in only 1 case. By age group, the most common disease was hydronephrosis in the 0–5 age group, monosymptomatic enuresis in the 6–11 age group, and asymptomatic proteinuria in the 12–17 age group. The most commonly used type of the fully automatic urinary particle analyzer was the UF-5000, with 174 cases, followed by the UF-1500 with 99 cases, and the UF-1000i with 7 cases. The measurement method for urine Cre was the enzyme method in all cases. Figure 1 shows a scatter plot of the overall urine RBC/Cre, while Fig. 2 shows scatter plots of urine RBC/Cre by age and sex. Table 2 shows the median, 2.5th percentile, and 97.5th percentile values of urine RBC and urine RBC/Cre by age and sex. No significant differences were observed in the median urine RBC among three age groups, and the same applied to the 2.5th percentile and 97.5th percentile values for urine RBC. However, urine RBC/Cre tended to increase with decreasing age. In addition, urine RBC/Cre values tended to be higher in males than in females in the 0–5 age group, while the opposite trend was observed in the 12–17 age group. Table 2 Detailed reference values of urine RBC/Cre according to age and sex urine RBC [/µL] urine RBC/Cre [×10 5 /mgCre] Age [years] n Median 2.5%ile 97.5%ile Median 2.5%ile 97.5%ile 0–17 280 2.5 0.1 22.9 3.7 0.2 90.7 0–5 123 2.0 0.1 22.8 8.5 0.6 142.0 6–11 89 2.7 0.1 18.0 3.0 0.2 33.4 12–17 68 1.4 0.1 25.9 1.4 0.0 14.7 Male urine RBC [/µL] urine RBC/Cre [×10 5 /mgCre] Age [years] n Median 2.5%ile 97.5%ile Median 2.5%ile 97.5%ile 0–17 162 2.3 0.1 19.4 3.8 0.2 118.5 0–5 88 2.2 0.1 20.4 8.2 0.6 175.7 6–11 45 2.2 0.1 12.7 2.7 0.1 35.0 12–17 29 2.5 0.1 11.8 1.1 0.0 5.8 Female urine RBC [/µL] urine RBC/Cre [×10 5 /mgCre] Age [years] n Median 2.5%ile 97.5%ile Median 2.5%ile 97.5%ile 0–17 118 2.7 0.1 31.7 3.5 0.2 57.7 0–5 35 1.9 0.2 32.6 9.2 0.5 95.0 6–11 44 2.9 0.1 20.2 4.0 0.3 19.3 12–17 39 2.8 0.1 31.4 1.7 0.2 20.0 Figure We used EZR to create the Figures. Discussion In this study, we established the first pediatric reference values for urine RBC/Cre. Our results indicate that urine RBC/Cre may vary with age and sex: although no significant differences were found, younger children tended to have higher RBC/Cre values, and differences between boys and girls emerge during adolescence (with adolescent girls tending to have higher upper-range RBC/Cre values, possibly due to menstrual contamination). The automated analyzers UF-1000i, UF-1500, and UF-5000 all use flow cytometry with laser-induced scattering and fluorescence detection for analyzing urine particles. Urine samples are diluted and mixed with staining reagents, then directed through a flow cell where a laser beam irradiates individual particles. pass in a single stream. Three types of light signals (Forward scattered light, Side scattered light, and Side fluorescent light) are generated, and by analyzing these light signals for, the analyzer quantitatively count and classifies formed elements such as red blood cells [ 4 , 5 ]. However, this measurement principle does not take urine concentration. Indeed, Yang reported that red blood cell counts increased with higher concentration and decreased with lower concentration [ 6 ]. By calculated the median, 2.5th percentile, and 97.5th percentile values for urine RBC/Cre, we defined reference ranges stratified by age and sex (Table 2 ). The overall reference range was 0.2–90.7/mgCre, but notable differences were observed across age groups: 0.6–142/mgCre in ages 0–5, 0.2–33.4/mgCre in ages 6–11, and 0.0-14.7/mgCre in ages 12–17. These differences likely reflect the lower urine Cre levels in younger children. Since we did not define a lower limit for urine Cre, urine RBC/Cre values in infants should be interpreted with particular caution. Furthermore, the 97.5th percentile value for adolescents aged 12–17 years was higher in girls than in boys, which may be influenced by residual menstrual contamination that could not be fully excluded. These were the first reference values for urine RBC/Cre. Hematuria is a primary symptom of glomerular disease, the causal relationship has not been proven, significantly associated with increased risks of end stage renal disease, rapid renal function progression, and all-cause mortality in patients with advanced-stage chronic kidney disease; therefore, the evaluation of hematuria has gained increasing importance [ 7 ]. Evaluation of hematuria using urine RBC/Cre could be more useful in clinical practice than conventional microscopic examination for urine RBC. There are three reasons. First, using an automated urine formed element analyzer, it is not affected by the examiner’s skill and enables stable measurement. Second, dividing urine RBC by urine Cre may allow for correction fore urine concentration. Conventional urine red blood cell counts do not account for urine concentration effect, so evaluation may have overestimated or underestimated glomerular disease. However, using urine RBC/Cre allows for correction similar to urine protein-to-creatinine ratio, likely reflecting the actual degree of hematuria more accurately. Finally, urine RBC/Cre can be easily calculated by dividing urine RBC detected by FCM by the simultaneously measured urine Cre. This value is expected to be widely utilized in daily clinical practice. There are some limitations to this study. First, there is a possibility that patients during menstruation have not been completely excluded. In fact, the 97.5th percentile value for urine RBC/Cre was higher in girls aged 12–17 than in boys. Second, the presence or absence of calcium oxalate has not been considered. Urine FCM may misidentify calcium oxalate as urine RBC, potentially leading to an overestimation of urine RBC/Cre [ 8 ]. Third, we have not confirmed the urine collection method. Particularly when catheterization is performed, damage to the urethral mucosa can cause blood to mix into the collected urine. However, situations requiring catheterization are very limited, such as for evaluating urinary tract infections. Therefore, it is unlikely that catheterization was performed for the diseases studied in this research, and the impact on these data is expected to be extremely small. Finally, the prevalence of each disease varies by age. For example, hydronephrosis is most common in children aged 0–5 years, while enuresis is most common in children aged 6–11 years, and asymptomatic proteinuria is most common in adolescents aged 12–17 years. However, since we focused on diseases that cannot cause hematuria, we consider this limitation to have no impact on these data. Conclusions This study provides the first reference values for the urine red blood cell-to-creatinine ratio (urine RBC/Cre) in children under 18 years of age. Similar to the urine protein-to-creatinine ratio, urine RBC/Cre corrects for urine concentration and enables a more accurate assessment of hematuria. Age- and sex-specific reference ranges were also established, which may facilitate more reliable interpretation of urinary findings in pediatric clinical practice. Declarations Author contributions: Hiroki Matsubayashi, Osamu Uemura, Naoya Fujita, and Katsuaki Kasahara contributed to the study’s conception and design. Data acquisition was performed by Hiroki Matsubayashi, Naoya Fujita, Yoshimitsu Gotoh, Hiroshi Uchida, and Ryoichi Kitagata. All authors read and approved the final manuscript. Acknowledgement: The authors thank Dr. Yoshimitsu Gotoh of department of Pediatric Nephrology at Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Hiroshi Uchida and Ryoichi Kitagata of department of Pediatrics at Hamamatsu University Hospital for their assistance with patient recruitment and clinical data collection. Compliance with Ethnical Standards: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board of the first author’s facility (approval number 4677) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Competing interests: The authors have declared that no conflict of interest exists. Human and Animal Rights: This article does not contain any studies with animals performed by any of the authors. Registration of clinical trials: Not applicable (This study is a retrospective observational study and did not involve clinical trial registration). Informed consent: The Institutional Review Board waived the requirement for informed consent due to the retrospective nature of study. References Chien TI, Kao JT, Liu HL, Lin PC, Hong JS, Hsieh HP, Chien M (2007) J. Urine sediment examination: A comparison of automated urinalysis systems and manual microscopy. Clin Chim Acta 384:28–34 Hogg RJ, Furth S, Lemley KV, Portman R, Schwartz GJ, Coresh J, Balk E, Lau J, Levin A, Kausz A, T, Eknoyan G, Levey AS (2003) National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease in Children and Adolescents: Evaluation, Classification, and Stratification. Pediatrics 111:1416–1421 Zhai P, Huang Y, Yue S, Yang X, Luo J, Zhang Y, Mei X, Bi L, Zhai W, Ren X, Yang Y, Zheng X, Yamamoto T (2022) Diagnostic efficacy and influence factors of urinary protein/creatinine ratio replacing 24-h urine protein as an evaluator of proteinuria in children. Int Urol Nephrol 54(6):1409–1416 Cho H, Yoo J, Kim H, Jang H, Kim Y, Chae H (2022) Diagnostic Characteristics of Urinary Red Blood Cell Distribution Incorporated in UF-5000 for Differentiation of Glomerular and Non-Glomerular Hematuria. Ann Lab Med 42(2):160–168 Nakayama A, Tsuburai H, Ebina H, Kino F (2018) Outline and Features of UF-5000, Fully Automated Urine Particle Analyzer. Sysmex J Int 28(1):1–21 Yang WS (2021) Automated urine sediment analyzers underestimate the severity of hematuria in glomerular diseases. Sci Rep 11(1):20981 Lin HY, Yen C, Lim L, Hwang D, Tsai J, Hwang S, Hung C, Chen H (2015) Microscopic Haematuria and Clinical Outcomes in Patients With Stage 3–5 Nondiabetic Chronic Kidney Disease. Sci Rep 5:15242 Simhadri PK, Rout P, Leslie SW (2025) Urinary Crystals Identification and Analysis. StatPearlsAccessed on October 25 Cite Share Download PDF Status: Posted Version 1 posted 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. 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1","display":"","copyAsset":false,"role":"figure","size":39235,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plot of urine RBC/Cre for overall\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8625088/v1/c52887b1f4bfd47dec712130.png"},{"id":101205415,"identity":"406fe3f3-dc52-4516-8d52-7e7f0cf3d3c1","added_by":"auto","created_at":"2026-01-27 09:49:20","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":43052,"visible":true,"origin":"","legend":"\u003cp\u003eScatter plots of urine RBC/Cre by age and sex\u003c/p\u003e\n\u003cp\u003eA. Boys aged 0-5years, B. Boys aged 6-11 years, C. Boys aged 12-17 years, D. Girls aged 0-5years, E. Girls aged 6-11 years, F. Girls aged 12-17 years\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8625088/v1/585234d5639da5a22042b6e3.png"},{"id":103050448,"identity":"3355b16b-d4fa-4f77-9797-d08d81f08224","added_by":"auto","created_at":"2026-02-20 07:50:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":482432,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8625088/v1/d5586947-1ad6-415a-a170-c8ac5f50211d.pdf"}],"financialInterests":"","formattedTitle":"Reference Range for Urine Red Blood Cell-to-Creatinine Ratio in Japanese Children","fulltext":[{"header":"Introduction","content":"\u003cp\u003eUrinalysis is essential in the diagnosis and management of kidney disease. Hematuria is as important parameter as proteinuria in screening tests, diagnosis of kidney disease, and assessing treatment efficacy.\u003c/p\u003e \u003cp\u003eFor the diagnosis of hematuria, the dipstick test for hematuria and the visual examination of red blood cell counts in urine sediment have been commonly used. However, this method had the drawbacks of being dependent on the skill of the examiner and for not accounting for the degree of urine concentration [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eUrine flow cytometry (urine FCM), a method for testing formed elements in urine, has been increasingly used in various medical institutions in recent years. This method is performed automatically using urine FCM testing equipment, which is considered to eliminate the bias associated with the skill of the examiner [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHowever, urine FCM measurement values also do not account for urine concentration and may not provide accurate evaluations.\u003c/p\u003e \u003cp\u003eThe urine protein-to-creatinine ratio, calculated by dividing urine protein values by urine creatinine (urine Cre), has been reported to correlate with urine protein values obtained through 24-hour urine collection and is widely used for evaluating proteinuria as it can correct for urine concentration [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, the red blood cell count obtained by the urine sediment visual inspection method is not continuous value, making it impossible to calculate the urine Cre ratio.\u003c/p\u003e \u003cp\u003eGiven this background, we hypothesized that a urine RBC/Cre \u0026ndash; calculated by dividing a continuously measured urine RBC counts from FCM by the urine Cre \u0026ndash; would allow a more accurate assessment of hematuria independent of examiner skill or urine concentration. To date, no reference values for urine RBC/Cre in children have been reported, underscoring the need for this study.\u003c/p\u003e \u003cp\u003eThe objective of this study is to establish reference values for urine RBC/Cre based on past urine test results from subjects considered to have no underlying renal disease causing hematuria.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e\u0026lt;Study design and data collection\u0026gt;\u003c/p\u003e\n\u003cp\u003eIn this retrospective study, we reviewed the medical records of pediatric participants aged 18 years or younger who underwent urinalysis at each Seirei Hamamatsu General Hospital, Aichi Children’s Health and Medical Center, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital or Hamamatsu University Hospital between February 2016 and December 2024, and diagnosed with monosymptomatic enuresis, mild hydronephrosis, orthostatic proteinuria, or short stature. The definitions of each diseases are as follows:\u0026nbsp;\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003emonosymptomatic enuresis\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eIntermittent urinary incontinence during sleep in children aged 5 years or older, without daytime urinary incontinence or other lower urinary tract symptoms\u003c/p\u003e\n\u003col start=\"2\"\u003e\n \u003cli\u003emild hydronephrosis\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eDefined grade 1 by the Society for Fetal Urology classification (SFU) and no hydroureter\u003c/p\u003e\n\u003col start=\"3\"\u003e\n \u003cli\u003eorthostatic proteinuria\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eThe presence of protein in urine during upright posture but not when supine\u003c/p\u003e\n\u003cp\u003eWe diagnosed orthostatic proteinuria based on the normal morning urine on a 3-point urine collection method, or normal urine before a forward-bending test\u003c/p\u003e\n\u003col start=\"4\"\u003e\n \u003cli\u003eshort stature\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003eLimited to familial short stature or constitutional short stature\u003c/p\u003e\n\u003cp\u003eThe exclusion criteria were as follows: (1) patients with a history of hematuria; (2) patients with a diagnosis that may affect urine finding in medical records; (3) patients with congenital anomalies of the kidney and urinary tract (CAKUT) excluding SFU grade 1 hydronephrosis; (4) patients for whom urine FCM and urine Cre test were not performed on the same specimen; (5) patients who were menstruating at the time of urine test; (6) patients considered inappropriate for analysis by the attending physician; (7) patients who refused to participate in this study.\u003c/p\u003e\n\u003cp\u003eWe obtained the following data from medical records retrospectively: date of birth, sex, diagnosis, date of the urine sample was collected, data of urine test using urine FCM, type of the fully automatic urinary particle analyzer, method of urine Cre measurement (enzyme method or Jaffe method), urine sediment, urine RBC (calculated using urine FCM). We used only one urine sample per patient, and it should be the first sample in which urine RBC and urine Cre are measured (morning urine is acceptable). Based on the collected these values, urine RBC was divided by urine Cre to calculate urine RBC/Cre. The urine RBC/Cre was expressed in units of [×10\u003csup\u003e5\u003c/sup\u003e/mgCre].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026lt;Reference values of urine RBC/Cre\u0026gt;\u003c/p\u003e\n\u003cp\u003eThe reference value for urine RBC/Cre for each age group and sex were calculated from the collected data. Values by age were summarized by age group (0 to 5 years, 6 to 11 years, 12 to 17 years) and sex. We rounded off to the nearest thousandth of the urine RBC/Cre values.\u003c/p\u003e\n\u003cp\u003eThe median, 2.5\u003csup\u003eth\u003c/sup\u003e percentile, and 97.5\u003csup\u003eth\u003c/sup\u003e percentile values were calculated for each age group and sex, and the range between the 2.5\u003csup\u003eth\u003c/sup\u003e percentile and 97.5\u003csup\u003eth\u003c/sup\u003e percentile values was defined as the reference range.\u003c/p\u003e\n\u003cp\u003e\u0026lt;Analysis\u0026gt;\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using EZR (Easy R), which is a graphical user interface for R developed by the Jichi Medical University Saitama Medical Center.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u0026lt;Characteristics of the study population (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u0026gt;\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of participants and data\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e280\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e123 (43.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u0026ndash;11 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89 (31.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u0026ndash;17 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 (24.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e162 (57.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118 (42.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emonosymptomatic enuresis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e72 (25.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003emild hydronephrosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e116 (41.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eorthostatic proteinuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e91 (32.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eshort stature\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of the fully automatic urinary particle analyzer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUF-5000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e174 (62.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUF-1500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99 (35.4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUF-1000i\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethod of urine Cre measurement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEnzyme method\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e280 (100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJaffe method\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"2\"\u003eData are presented as \u003cem\u003en\u003c/em\u003e (%)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e A total of 280 children met the inclusion criteria. These participants drawn from the four facilities listed above and comprised 162 boys (57.9%) and 118 girls (42.1%). The age distribution of the cohort was as follows: 123 children (44%) were 0\u0026ndash;5 years old, 89 (32%) were 6\u0026ndash;11 years old, and 68 (24%) were 12\u0026ndash;17 years old.\u003c/p\u003e \u003cp\u003eThe most common disease was hydronephrosis, with 116 cases. This was followed by orthostatic proteinuria in 91 cases, monosymptomatic enuresis in 72 cases, and short stature in only 1 case.\u003c/p\u003e \u003cp\u003eBy age group, the most common disease was hydronephrosis in the 0\u0026ndash;5 age group, monosymptomatic enuresis in the 6\u0026ndash;11 age group, and asymptomatic proteinuria in the 12\u0026ndash;17 age group.\u003c/p\u003e \u003cp\u003eThe most commonly used type of the fully automatic urinary particle analyzer was the UF-5000, with 174 cases, followed by the UF-1500 with 99 cases, and the UF-1000i with 7 cases.\u003c/p\u003e \u003cp\u003eThe measurement method for urine Cre was the enzyme method in all cases.\u003c/p\u003e \u003cp\u003e\u0026lt;Reference values of urine RBC/Cre\u0026gt;\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows a scatter plot of the overall urine RBC/Cre, while Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows scatter plots of urine RBC/Cre by age and sex. Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the median, 2.5th percentile, and 97.5th percentile values of urine RBC and urine RBC/Cre by age and sex. No significant differences were observed in the median urine RBC among three age groups, and the same applied to the 2.5th percentile and 97.5th percentile values for urine RBC. However, urine RBC/Cre tended to increase with decreasing age. In addition, urine RBC/Cre values tended to be higher in males than in females in the 0\u0026ndash;5 age group, while the opposite trend was observed in the 12\u0026ndash;17 age group.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDetailed reference values of urine RBC/Cre according to age and sex\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eurine RBC [/\u0026micro;L]\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eurine RBC/Cre [\u0026times;10\u003csup\u003e5\u003c/sup\u003e/mgCre]\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge [years]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.5%ile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e97.5%ile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.5%ile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e97.5%ile\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e90.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e123\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e142.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u0026ndash;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e33.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u0026ndash;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e14.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c9\" namest=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eurine RBC [/\u0026micro;L]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eurine RBC/Cre [\u0026times;10\u003csup\u003e5\u003c/sup\u003e/mgCre]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge [years]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.5%ile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e97.5%ile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.5%ile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e97.5%ile\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e162\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e118.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e175.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u0026ndash;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e35.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u0026ndash;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e5.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"8\" nameend=\"c9\" namest=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eurine RBC [/\u0026micro;L]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c9\" namest=\"c7\"\u003e \u003cp\u003eurine RBC/Cre [\u0026times;10\u003csup\u003e5\u003c/sup\u003e/mgCre]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge [years]\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003en\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.5%ile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e97.5%ile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMedian\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.5%ile\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e97.5%ile\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e118\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e57.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u0026ndash;5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e95.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u0026ndash;11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e19.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e12\u0026ndash;17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e20.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eFigure\u003c/span\u003e\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eWe used EZR to create the Figures.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we established the first pediatric reference values for urine RBC/Cre. Our results indicate that urine RBC/Cre may vary with age and sex: although no significant differences were found, younger children tended to have higher RBC/Cre values, and differences between boys and girls emerge during adolescence (with adolescent girls tending to have higher upper-range RBC/Cre values, possibly due to menstrual contamination).\u003c/p\u003e \u003cp\u003eThe automated analyzers UF-1000i, UF-1500, and UF-5000 all use flow cytometry with laser-induced scattering and fluorescence detection for analyzing urine particles. Urine samples are diluted and mixed with staining reagents, then directed through a flow cell where a laser beam irradiates individual particles. pass in a single stream. Three types of light signals (Forward scattered light, Side scattered light, and Side fluorescent light) are generated, and by analyzing these light signals for, the analyzer quantitatively count and classifies formed elements such as red blood cells [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, this measurement principle does not take urine concentration. Indeed, Yang reported that red blood cell counts increased with higher concentration and decreased with lower concentration [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBy calculated the median, 2.5th percentile, and 97.5th percentile values for urine RBC/Cre, we defined reference ranges stratified by age and sex (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The overall reference range was 0.2\u0026ndash;90.7/mgCre, but notable differences were observed across age groups: 0.6\u0026ndash;142/mgCre in ages 0\u0026ndash;5, 0.2\u0026ndash;33.4/mgCre in ages 6\u0026ndash;11, and 0.0-14.7/mgCre in ages 12\u0026ndash;17. These differences likely reflect the lower urine Cre levels in younger children. Since we did not define a lower limit for urine Cre, urine RBC/Cre values in infants should be interpreted with particular caution. Furthermore, the 97.5th percentile value for adolescents aged 12\u0026ndash;17 years was higher in girls than in boys, which may be influenced by residual menstrual contamination that could not be fully excluded.\u003c/p\u003e \u003cp\u003eThese were the first reference values for urine RBC/Cre.\u003c/p\u003e \u003cp\u003eHematuria is a primary symptom of glomerular disease, the causal relationship has not been proven, significantly associated with increased risks of end stage renal disease, rapid renal function progression, and all-cause mortality in patients with advanced-stage chronic kidney disease; therefore, the evaluation of hematuria has gained increasing importance [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eEvaluation of hematuria using urine RBC/Cre could be more useful in clinical practice than conventional microscopic examination for urine RBC. There are three reasons. First, using an automated urine formed element analyzer, it is not affected by the examiner\u0026rsquo;s skill and enables stable measurement. Second, dividing urine RBC by urine Cre may allow for correction fore urine concentration. Conventional urine red blood cell counts do not account for urine concentration effect, so evaluation may have overestimated or underestimated glomerular disease. However, using urine RBC/Cre allows for correction similar to urine protein-to-creatinine ratio, likely reflecting the actual degree of hematuria more accurately. Finally, urine RBC/Cre can be easily calculated by dividing urine RBC detected by FCM by the simultaneously measured urine Cre. This value is expected to be widely utilized in daily clinical practice.\u003c/p\u003e \u003cp\u003eThere are some limitations to this study. First, there is a possibility that patients during menstruation have not been completely excluded. In fact, the 97.5th percentile value for urine RBC/Cre was higher in girls aged 12\u0026ndash;17 than in boys. Second, the presence or absence of calcium oxalate has not been considered. Urine FCM may misidentify calcium oxalate as urine RBC, potentially leading to an overestimation of urine RBC/Cre [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Third, we have not confirmed the urine collection method. Particularly when catheterization is performed, damage to the urethral mucosa can cause blood to mix into the collected urine. However, situations requiring catheterization are very limited, such as for evaluating urinary tract infections. Therefore, it is unlikely that catheterization was performed for the diseases studied in this research, and the impact on these data is expected to be extremely small. Finally, the prevalence of each disease varies by age. For example, hydronephrosis is most common in children aged 0\u0026ndash;5 years, while enuresis is most common in children aged 6\u0026ndash;11 years, and asymptomatic proteinuria is most common in adolescents aged 12\u0026ndash;17 years. However, since we focused on diseases that cannot cause hematuria, we consider this limitation to have no impact on these data.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis study provides the first reference values for the urine red blood cell-to-creatinine ratio (urine RBC/Cre) in children under 18 years of age. Similar to the urine protein-to-creatinine ratio, urine RBC/Cre corrects for urine concentration and enables a more accurate assessment of hematuria. Age- and sex-specific reference ranges were also established, which may facilitate more reliable interpretation of urinary findings in pediatric clinical practice.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAuthor contributions: Hiroki Matsubayashi, Osamu Uemura, Naoya Fujita, and Katsuaki Kasahara contributed to the study\u0026rsquo;s conception and design. Data acquisition was performed by Hiroki Matsubayashi, Naoya Fujita, Yoshimitsu Gotoh, Hiroshi Uchida, and Ryoichi Kitagata. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgement: The authors thank Dr. Yoshimitsu Gotoh of department of Pediatric Nephrology at Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Hiroshi Uchida and Ryoichi Kitagata of department of Pediatrics at Hamamatsu University Hospital for their assistance with patient recruitment and clinical data collection.\u003c/p\u003e\n\u003cp\u003eCompliance with Ethnical Standards: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board of the first author\u0026rsquo;s facility (approval number 4677) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003eCompeting interests: The authors have declared that no conflict of interest exists.\u003c/p\u003e\n\u003cp\u003eHuman and Animal Rights: This article does not contain any studies with animals performed by any of the authors.\u003c/p\u003e\n\u003cp\u003eRegistration of clinical trials: Not applicable (This study is a retrospective observational study and did not involve clinical trial registration).\u003c/p\u003e\n\u003cp\u003eInformed consent: The Institutional Review Board waived the requirement for informed consent due to the retrospective nature of study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eChien TI, Kao JT, Liu HL, Lin PC, Hong JS, Hsieh HP, Chien M (2007) J. Urine sediment examination: A comparison of automated urinalysis systems and manual microscopy. Clin Chim Acta 384:28\u0026ndash;34\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHogg RJ, Furth S, Lemley KV, Portman R, Schwartz GJ, Coresh J, Balk E, Lau J, Levin A, Kausz A, T, Eknoyan G, Levey AS (2003) National Kidney Foundation\u0026rsquo;s Kidney Disease Outcomes Quality Initiative Clinical Practice Guidelines for Chronic Kidney Disease in Children and Adolescents: Evaluation, Classification, and Stratification. Pediatrics 111:1416\u0026ndash;1421\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhai P, Huang Y, Yue S, Yang X, Luo J, Zhang Y, Mei X, Bi L, Zhai W, Ren X, Yang Y, Zheng X, Yamamoto T (2022) Diagnostic efficacy and influence factors of urinary protein/creatinine ratio replacing 24-h urine protein as an evaluator of proteinuria in children. Int Urol Nephrol 54(6):1409\u0026ndash;1416\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCho H, Yoo J, Kim H, Jang H, Kim Y, Chae H (2022) Diagnostic Characteristics of Urinary Red Blood Cell Distribution Incorporated in UF-5000 for Differentiation of Glomerular and Non-Glomerular Hematuria. Ann Lab Med 42(2):160\u0026ndash;168\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNakayama A, Tsuburai H, Ebina H, Kino F (2018) Outline and Features of UF-5000, Fully Automated Urine Particle Analyzer. Sysmex J Int 28(1):1\u0026ndash;21\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang WS (2021) Automated urine sediment analyzers underestimate the severity of hematuria in glomerular diseases. Sci Rep 11(1):20981\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLin HY, Yen C, Lim L, Hwang D, Tsai J, Hwang S, Hung C, Chen H (2015) Microscopic Haematuria and Clinical Outcomes in Patients With Stage 3\u0026ndash;5 Nondiabetic Chronic Kidney Disease. Sci Rep 5:15242\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSimhadri PK, Rout P, Leslie SW (2025) Urinary Crystals Identification and Analysis. StatPearlsAccessed on October 25\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8625088/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8625088/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eHematuria is important parameter for diagnosis of kidney disease and assessing treatment efficacy. However, reference values for the urine RBC-to-creatinine ratio (urine RBC/Cre), caluculated by dividing urine creatinine for correcting urine concentration, are not provided.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe retrospectively analyzed urine RBC counts and urine Cre values in children aged 18 years or younger from four facilities between February 2016 and December 2024. From these, we calculated the urine RBC/Cre using the formula: urine RBC [/\u0026micro;L] / urine Cre [mg/dL] \u0026times; 10\u003csup\u003e5\u003c/sup\u003e. The calculated urine RBC/Cre results were expressed in units of [\u0026times;10\u003csup\u003e5\u003c/sup\u003e/mgCre]. We established detailed reference values (the median, 2.5th percentile, and 97.5th percentile) for this urine RBC/Cre by sex and age group.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eBased on the aggregated urine RBC/Cre of 280 participants, we established detailed reference values by age and sex. The overall median urine RBC/Cre was 3.7 [\u0026times;10\u003csup\u003e5\u003c/sup\u003e/mgCre]. The median value was 3.8 for boys and 3.5 for girls. Age-specific median values in boys vs. girls were 8.2 vs. 9.2 for ages 0\u0026ndash;5 years, 2.7 vs. 4.0 for ages 6\u0026ndash;11 years, and 1.1 vs. 1.7 for ages 12\u0026ndash;17 years. Age-specific 97.5th percentile values in boys vs. girls were 175.5 vs. 95.0 for ages 0\u0026ndash;5 years, 35.5 vs. 19.3 for ages 6\u0026ndash;11 years, and 5.8 vs. 20.0 for ages 12\u0026ndash;17 years.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis study provides the first reference values for urine RBC/Cre in children. This may facilitate more reliable interpretation of urinary findings in pediatric clinical practice.\u003c/p\u003e","manuscriptTitle":"Reference Range for Urine Red Blood Cell-to-Creatinine Ratio in Japanese Children","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-25 10:20:48","doi":"10.21203/rs.3.rs-8625088/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5680e6ef-9c9c-4dee-ba9a-4c01244ee070","owner":[],"postedDate":"January 25th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-19T22:07:16+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-25 10:20:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8625088","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8625088","identity":"rs-8625088","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}