Handheld urine total dissolved solids and ultrasound-detected renal stones smaller than 5 mm in infants: a prospective pilot comparative study

Handheld urine total dissolved solids and ultrasound-detected renal stones smaller than 5 mm in infants: a prospective pilot comparative study | 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 Handheld urine total dissolved solids and ultrasound-detected renal stones smaller than 5 mm in infants: a prospective pilot comparative study YUSUF ATAKAN BALTRAK, HASAN DELİAGA This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9405719/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 Infants with asymptomatic renal stones smaller than 5 mm are often managed conservatively with ultrasonographic follow-up and hydration counselling. In diapered children, repeated outpatient urine assessment is difficult because first-morning samples, 24-hour urine collections, and laboratory osmolality testing are often impractical. Handheld total dissolved solids (TDS) meters provide rapid conductivity-based readings from small urine volumes, but the biological meaning of these readings in infant urine is uncertain and they are not validated equivalents of established urine concentration measures. This pilot study investigated whether handheld urine TDS values are associated with ultrasound-detected renal stones smaller than 5 mm in infants younger than 24 months. Methods This prospective pilot comparative study included infants younger than 24 months with and without ultrasound-detected renal stones smaller than 5 mm. Non-first-morning daytime spot urine samples were collected on three non-consecutive days within a 10-day period, and mean TDS values were calculated. Receiver operating characteristic (ROC) analysis was used descriptively to assess sample-level separation, and multivariable logistic regression adjusted for age and sex was used to examine association. Results Seventy-four infants were included: 37 cases and 37 controls. Mean urine TDS was higher in infants with stones than in controls (480.6 ± 171.6 vs 306.8 ± 67.9 ppm; p < 0.01), corresponding to a large effect size (Cohen’s d ≈ 1.3). ROC analysis showed an area under the curve of 0.80 (95% CI 0.696–0.900). In multivariable analysis adjusted for age and sex, each 100 ppm increase in TDS was associated with higher odds of stone presence (adjusted OR 2.92; 95% CI 1.73–4.93; p < 0.0001). Conclusions In this pilot cohort, handheld urine TDS values were higher in infants with ultrasound-detected renal stones smaller than 5 mm than in stone-negative controls. These findings indicate an association between stone status and a device-derived conductivity signal, but they do not establish diagnostic validity or confirm that TDS reflects urine concentration alone. Direct analytical validation and longitudinal studies are needed before any clinical role can be considered. Infant nephrolithiasis renal stones ultrasonography urine conductivity hydration total dissolved solids Figures Figure 1 Background Pediatric nephrolithiasis is increasingly recognized, and ultrasonography remains the preferred imaging modality for diagnosis and follow-up because it avoids exposure to ionizing radiation [ 1 , 2 ]. In selected children, asymptomatic renal stones smaller than 5 mm are commonly managed conservatively with imaging surveillance, hydration counselling, and metabolic evaluation [ 3 – 5 ]. Adequate hydration is central to stone prevention because concentrated urine contributes to lithogenesis [ 4 , 6 – 8 ]. In routine practice, urine concentration is typically assessed by urine osmolality or specific gravity [ 6 – 8 ]. In infants, however, repeated urine assessment between imaging visits is difficult. First-morning samples are not always feasible, 24-hour urine collection is rarely practical, and laboratory testing may not be readily available in outpatient settings. Handheld TDS meters generate rapid conductivity-based readings from small urine volumes. Such devices may appear attractive for repeated outpatient measurement in diapered infants, but important interpretive limitations remain. Conductivity-derived TDS is not equivalent to urine osmolality and should not be regarded as a validated hydration biomarker. Rather, it represents a device-derived signal influenced by ionic composition, urine matrix characteristics, and meter-specific conversion methods [ 9 , 10 ]. In infant urine, where feeding patterns, recent intake, and urinary composition may vary substantially, the biological meaning of a handheld TDS reading is uncertain. To our knowledge, no published study has specifically examined handheld urine TDS values in infants with ultrasound-detected renal stones smaller than 5 mm. We therefore undertook this pilot study to determine whether mean handheld urine TDS differs between infants with and without ultrasound-detected renal stones smaller than 5 mm. We also sought to generate preliminary data that could inform future analytical validation studies. Methods Study design and setting This was a prospective pilot comparative study conducted in a tertiary paediatric urology outpatient clinic between January and December 2025. Urine TDS measurements and ultrasound-based stone status were assessed during the same study period. The study was designed to examine association rather than causality, prediction, or diagnostic performance. Participants Cases were infants younger than 24 months with asymptomatic renal stones smaller than 5 mm identified on ultrasonography. Controls were stone-negative infants recruited consecutively from the same outpatient ultrasonography population during the same period in order to reduce referral-setting differences between groups. Cases were excluded if they had symptomatic stone episodes, obstructive stones, urinary tract infection at the time of sampling, acute systemic illness, ongoing treatment for acute metabolic or electrolyte disorders, visible sample contamination, or incomplete data. Controls were excluded if they had previous urolithiasis, current urinary tract infection, fever, acute gastroenteritis with vomiting or diarrhoea, chronic kidney disease, major congenital urinary anomalies, diuretic use, visible sample contamination, incomplete data, or conditions known to affect fluid or electrolyte balance. No individual matching was performed. Age and sex were prespecified covariates. Ultrasonography Renal and bladder ultrasonography was performed for routine clinical indications and interpreted by a paediatric radiologist blinded to urine TDS results. Stone status was based on the final radiology report. Cases were defined as infants with a renal stone or calculus smaller than 5 mm on ultrasonography. Controls had no renal stones reported. Because ultrasound may misclassify very small calculi, particularly lesions smaller than 5 mm, stone status was treated as an imaging-based clinical classification rather than a reference standard. Urine sampling and TDS measurement Because first-morning and 24-hour urine collection are often impractical in infants, non-first-morning daytime spot urine samples were used. Samples were collected during clinic hours (09:00–15:00) using paediatric urine collection bags on three non-consecutive days within a 10-day period. Mean TDS values were calculated from these repeated measurements to reduce the influence of short-term within-subject variation. Feeding patterns included breast milk, formula feeding, and complementary foods according to age. Dietary composition, feeding timing, and intake immediately before sampling were not standardized. Urine was transferred to clean single-use containers after collection, and samples with visible stool contamination were excluded. TDS was measured using a handheld conductivity-based meter (OHAUS ST 20 T-B) with automatic temperature compensation. The device was calibrated daily according to the manufacturer’s instructions. Each sample was measured twice consecutively, and the mean of the two readings was used for analysis. Results were recorded in ppm as device-based conductivity values. These readings were not treated as equivalents of urine osmolality or direct biochemical total solute concentration. Urine specific gravity was obtained by routine dipstick urinalysis at the time of clinical evaluation and was used descriptively. Formal comparison with urine osmolality or refractometric specific gravity was not performed. Outcomes The primary outcome was renal stone status on ultrasonography (present or absent). The primary explanatory variable was mean urine TDS in ppm, averaged from three non-consecutive daytime measurements. The study did not evaluate hydration status against a biochemical reference standard and did not assess longitudinal outcomes such as stone growth, persistence, recurrence, or response to hydration counselling. Statistical analysis No formal a priori sample size calculation was performed because of the exploratory pilot design. Sample size was determined by the number of eligible infants during the study period. Continuous variables were presented as mean ± standard deviation or median with interquartile range, and categorical variables as counts and percentages. Between-group comparisons were performed using Welch’s t-test for continuous variables and the chi-square test or Fisher’s exact test for categorical variables. Effect size was expressed as Cohen’s d. ROC analysis was used descriptively to assess sample-level separation of TDS values by stone status. The area under the curve (AUC) with 95% confidence interval was reported. Because of the pilot design, balanced sampling, and uncertainty regarding the biological meaning of TDS, ROC findings were not used to derive clinically applicable thresholds. Multivariable logistic regression was used to model stone presence with mean TDS per 100 ppm increase, age in months, and sex as prespecified covariates. TDS was specified a priori as a linear term per 100 ppm increase in order to preserve model simplicity in this pilot dataset. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were reported. Model calibration was assessed with the Hosmer–Lemeshow goodness-of-fit test. A sensitivity analysis excluding the highest decile of TDS values was performed to assess whether extreme readings disproportionately influenced the association. A two-sided p value < 0.05 was considered statistically significant. Analyses were performed using IBM SPSS Statistics version 29.0. Ethics Ethics approval was obtained from the local institutional ethics committee (approval number: 226/2025) in accordance with the Declaration of Helsinki. Written informed consent for participation and publication of anonymized data was obtained from the parents or legal guardians of all participants. Clinical trial number: not applicable. Results Participant characteristics A total of 74 infants were included in the final analysis: 37 in the stone group and 37 in the control group. Age and sex distributions were similar between groups (Table 1 ). Mean urinary TDS was higher in infants with stones than in controls (480.6 ± 171.6 ppm vs 306.8 ± 67.9 ppm; p < 0.01), with a large effect size (Cohen’s d ≈ 1.3). Urine dipstick specific gravity values were similar between groups. Table 1 Demographic characteristics and urine total dissolved solids values in infants with ultrasound-detected renal stones smaller than 5 mm and stone-negative controls. Variable Stone group (n = 37) Control group (n = 37) p value Age (months), median (IQR) 15.3 (11.2–20.6) 16.4 (10.5–19.6) > 0.05 Male, n (%) 21 (56.7) 24 (64.9) > 0.05 Female, n (%) 16 (43.3) 13 (35.1) > 0.05 TDS (ppm), mean ± SD 480.6 ± 171.6 306.8 ± 67.9 < 0.01 TDS (ppm), median (min–max) 489.0 (169–762) 297.1 (134–442) 0.05 Baseline demographic characteristics and urine total dissolved solids (TDS) measurements of study participants according to renal stone status. Continuous variables are presented as mean ± standard deviation or median (interquartile range), and categorical variables as number (percentage). Abbreviations: TDS, total dissolved solids; IQR, interquartile range; SD, standard deviation. Urinalysis and metabolic findings in the stone group Within the stone group, routine urinalysis and available spot urinary metabolic findings were heterogeneous. Microscopic hematuria and pyuria were present in a subset of infants, whereas proteinuria and crystalluria were less common. Hyperuricosuria and hypercalciuria were among the most frequent spot urinary metabolic abnormalities. No detectable metabolic abnormality was identified in 11 of 37 infants (Table 2). Comparable structured metabolic data were not available for controls; therefore, these findings are descriptive only and cannot be used to determine whether group differences in TDS reflect stone status itself, differences in urine composition, or both. Table 2 Urinalysis and spot urinary metabolic findings among infants with ultrasound-detected renal stones smaller than 5 mm. Variable Stone group (n = 37) Urine specific gravity, median (IQR) 1.016 (1.015–1.018) Urine pH, median (IQR) 6.0 (5.5–6.5) Microscopic hematuria, n (%) 11 (29.7) Pyuria, n (%) 9 (24.3) Proteinuria, n (%) 4 (10.8) Crystalluria, n (%) 3 (8.1) Hypercalciuria, n/N (%) 12/37 (32.4) Hyperoxaluria, n/N (%) 5/37 (13.5) Hypocitraturia, n/N (%) 4/37 (10.8) Hyperuricosuria, n/N (%) 16/37 (43.2) Hypomagnesuria, n/N (%) 9/37 (24.3) Cystinuria, n/N (%) 1/37 (2.7) No detected metabolic abnormality, n/N (%) 11/37 (29.7) Descriptive urinalysis and spot urinary metabolic characteristics of infants in the stone group. Continuous variables are presented as median (interquartile range), and categorical variables as number/total number (percentage), where applicable. Metabolic findings are reported descriptively and were not compared statistically with controls. Abbreviations: IQR, interquartile range. ROC analysis ROC analysis showed moderate sample-level separation of mean TDS values according to stone status, with an AUC of 0.80 (95% CI 0.696–0.900). Given the pilot design, balanced sampling, and uncertainty about what TDS captures biologically, this finding was interpreted descriptively only. Multivariable analysis In multivariable logistic regression adjusted for age and sex, mean TDS remained associated with stone presence. Each 100 ppm increase in TDS was associated with higher odds of stone detection (adjusted OR 2.92; 95% CI 1.73–4.93; p < 0.0001). The Hosmer–Lemeshow test showed no evidence of poor model fit (p = 0.64). Sensitivity analysis excluding the highest decile of TDS values produced similar estimates, suggesting that the observed association was not driven only by extreme measurements. Discussion This pilot study found that infants with ultrasound-detected renal stones smaller than 5 mm had higher handheld urine TDS values than stone-negative controls. The association remained statistically significant after adjustment for age and sex. At face value, this suggests that stone status was associated with a higher device-derived conductivity signal in the sampled urine specimens. The interpretation of that association, however, is limited. Handheld urine TDS is not a validated equivalent of urine osmolality, and in this study it cannot be assumed to represent urine concentration alone. Conductivity-based measurements are influenced by ionic composition and by device-specific conversion methods [9,10]. In the present setting, higher TDS values may reflect more concentrated urine, differences in urinary solute composition, or a combination of both. That distinction is important because stone formation in infancy is multifactorial. A higher TDS value in the stone group does not mean that the device captured a specific lithogenic mechanism, nor does it establish that TDS is measuring hydration status. It is also plausible that urinary abnormalities more common in stone-forming infants, including differences in calcium, uric acid, or other ionic constituents, contributed to the higher readings. This concern is reinforced by the descriptive metabolic findings. Hyperuricosuria and hypercalciuria were relatively common in the stone group, but comparable structured metabolic data were not available for controls. As a result, the study cannot distinguish whether the observed difference in TDS primarily reflects stone status, differences in urine composition, differences in urine concentration, or overlap among these factors. A related point is the absence of a clear between-group difference in dipstick urine specific gravity. Because strip-based specific gravity has known analytical limitations [11], this does not invalidate the TDS finding. However, it does caution against treating TDS as a straightforward surrogate of conventional concentration measures. The discordance between these two urine measures supports the view that they may be capturing different physical or analytical properties of the specimen. The study also has important design limitations. Ultrasound-based classification of very small renal stones is imperfect and may have introduced outcome misclassification. Repeated spot sampling was used to reduce short-term variation, but within-subject reproducibility of TDS was not formally assessed. Urine collection by paediatric bag, daytime sampling, and non-standardized feeding patterns introduced additional biological and pre-analytical variability. Residual confounding from recent fluid intake, feeding interval, ambient temperature, and unmeasured urinary composition was likely. The multivariable model adjusted only for age and sex, which preserved parsimony but does not eliminate broader confounding. These limitations place the findings firmly in the exploratory domain. The study does not support clinical use of handheld TDS as a diagnostic test, a hydration biomarker, or a substitute for urine osmolality or refractometric specific gravity. Its main contribution is narrower: it shows that a handheld conductivity-derived urine signal differed between stone-positive and stone-negative infants in this pilot cohort. That limited finding may still be useful. In infants, repeated standard urine testing is often difficult, and simple device-based measurements are appealing for practical reasons. Before any clinical role can be considered, however, future studies need to establish what handheld TDS is actually measuring in urine. Direct analytical comparison with urine osmolality, refractometric specific gravity, and urinary solute composition in the same specimens is essential. Only after such validation would it be reasonable to examine whether serial TDS measurements have longitudinal clinical relevance for stone persistence, progression, recurrence, or response to hydration counselling. Conclusions In this prospective pilot comparative study, handheld urine TDS values were higher in infants with ultrasound-detected renal stones smaller than 5 mm than in stone-negative controls. These findings support an association between stone status and a device-derived conductivity signal, but they do not establish that TDS reflects urine concentration alone or that it has diagnostic value. Further analytical validation and longitudinal studies are required before any clinical application can be considered. Abbreviations AUC : Area under the curve CI : Confidence interval OR : Odds ratio ROC : Receiver operating characteristic SD : Standard deviation TDS : Total dissolved solids Declarations Acknowledgements The authors thank the patients and their families for their participation. Authors’ contributions Conceptualization: YAB Methodology: YAB, HD Data collection: YAB Formal analysis: YAB Writing – original draft: YAB Writing – review and editing: HD All authors read and approved the final manuscript. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate Ethics approval was obtained from Hatay Education and Research Hospital Ethics Committee (approval number: 226/2025). Written informed consent for participation was obtained from the parents or legal guardians of all participants. Trial registration Clinical trial number: not applicable. Consent for publication Written informed consent for publication of anonymized data was obtained from the parents or legal guardians of all participants. Competing interests The authors declare that they have no competing interests. They have no financial relationship with the manufacturer of the device used in this study. The authors declare that they have no competing interests and no financial, commercial, or personal relationship with the manufacturer or distributor of the handheld TDS device used in this study. References Hernandez J, Ellison JS, Lendvay TS. Current trends, evaluation, and management of pediatric nephrolithiasis. JAMA Pediatr. 2015;169(10):964–70. Grivas N, Thomas K, Drake T, Donaldson JF, Neisius A, Petřík A, et al. Imaging modalities and treatment of paediatric upper tract urolithiasis: a systematic review and update on behalf of the EAU Urolithiasis Guidelines Panel. J Pediatr Urol. 2020;16(3):220–34. Lombardo R, Tzelves L, Geraghty R, Davis NF, Neisius A, Petřík A, et al. Follow-up of urolithiasis patients after treatment: an algorithm from the EAU Urolithiasis Panel. World J Urol. 2024;42:1–10. Pearle MS, Goldfarb DS, Assimos DG, Curhan GC, Denu-Ciocca CJ, Matlaga BR, et al. Medical management of kidney stones: AUA guideline. J Urol. 2014;192(2):316–24. Kanno T, Takahashi T, Ito K, Okada T, Higashi Y, Yamada H. The natural history of asymptomatic renal stones ≤ 5 mm: comparison with ≥ 5 mm. J Endourol. 2020;34(11):1188–94. Skolarikos A, Straub M, Knoll T, Sarica K, Seitz C, Petřík A, Türk C. Metabolic evaluation and recurrence prevention for urinary stone patients: EAU guidelines. Eur Urol. 2015;67(4):750–63. Injeyan M, Bidault V, Bacchetta J, Bertholet-Thomas A. Hydration and nephrolithiasis in pediatric populations: specificities and current recommendations. Nutrients. 2023;15:728. Kang HW, Seo SP, Ha YS, Kim WT, Kim YJ, Yun SJ, et al. Twenty-four-hour urine osmolality as a representative index of adequate hydration and a predictor of recurrence in patients with urolithiasis. Int Urol Nephrol. 2019;51:1129–35. Manoni F, Fornasiero L, Ercolin M, Tinello A, Ferrian M, Valverde S, et al. Laboratory diagnosis of renal failure: urine conductivity and tubular function. Minerva Urol Nefrol. 2009;61(1):17–20. Fazil Marickar YM. Electrical conductivity and total dissolved solids in urine. Urol Res. 2010;38:233–5. Dörner K, Campos H, Börnsen H. Evaluation of the SG test strip. J Clin Chem Clin Biochem. 1984;22:419–25. Mao W, Zhang H, Xu Z, Geng J, Zhang Z, Wu J, et al. Relationship between urine specific gravity and the prevalence rate of kidney stone. Transl Androl Urol. 2020;10:184–94. Peerapen P, Thongboonkerd V. Kidney stone prevention. Adv Nutr. 2023;14(3):555–69. Additional Declarations No competing interests reported. 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. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9405719","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":625324681,"identity":"43113aa4-24d5-454d-bdc7-d36c75553edb","order_by":0,"name":"YUSUF ATAKAN BALTRAK","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDUlEQVRIiWNgGAWjYDCCA1DCgIG5AchKkAPzH+DXwtgA0cLYCNSTYAwWTCBFSyLILgZ8WvhuH37+4McZuzxz9oPtjytq0tLnhx1+CLTFTk63AbsWyXNpho09N5KLLXsSGxvPHMvJ3Xg7zQCoJdnY7AB2LQZnGAwbeD4wJ244ANTSwFaRu3F2AkjLgcRtOLWwf2z886E+ccP5h0At/yrSDWenfyCghcewmefG4cQNN4C2NLblJMhL5+C3RfIMT+FsmTPHE3fOeNg4s7EvzXCDdE7BgQQD3H7hO8O+4eObY9WJ2/mTD3xs+JYsLz87ffOHDxV2cri0YHEqWKUBscpBQL6BFNWjYBSMglEwEgAAs4Bz3dKfGY8AAAAASUVORK5CYII=","orcid":"","institution":"Hatay Education and Research Hospital","correspondingAuthor":true,"prefix":"","firstName":"YUSUF","middleName":"ATAKAN","lastName":"BALTRAK","suffix":""},{"id":625324682,"identity":"e2c4b15b-a685-4f1f-9bed-7bc2bfe5f2b8","order_by":1,"name":"HASAN DELİAGA","email":"","orcid":"","institution":"Bursa Yuksek Ihtisas Egitim Ve Arastirma Hastanesi","correspondingAuthor":false,"prefix":"","firstName":"HASAN","middleName":"","lastName":"DELİAGA","suffix":""}],"badges":[],"createdAt":"2026-04-13 14:54:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9405719/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9405719/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107620382,"identity":"05d60ea8-e4c9-4676-955f-c01dca7387ab","added_by":"auto","created_at":"2026-04-23 09:36:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":51961,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eReceiver operating characteristic curve of mean urine total dissolved solids values for discrimination of ultrasound-detected renal stone status in infants.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eReceiver operating characteristic (ROC) analysis of mean handheld urine total dissolved solids (TDS) measurements for differentiation between infants with ultrasound-detected renal stones smaller than 5 mm and stone-negative controls. The area under the curve was 0.80 (95% confidence interval 0.696–0.900), indicating moderate sample-level discriminatory performance in this pilot cohort. Threshold values shown on the figure are exploratory and presented for descriptive purposes only.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-9405719/v1/5f536c82f7fd7600b17767c3.png"},{"id":107707262,"identity":"3b04f6f4-f4f7-4290-9116-07e58762ef79","added_by":"auto","created_at":"2026-04-24 09:19:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":260965,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9405719/v1/adc033fe-1919-4415-a712-2ce46dd97173.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Handheld urine total dissolved solids and ultrasound-detected renal stones smaller than 5 mm in infants: a prospective pilot comparative study","fulltext":[{"header":"Background","content":"\u003cp\u003ePediatric nephrolithiasis is increasingly recognized, and ultrasonography remains the preferred imaging modality for diagnosis and follow-up because it avoids exposure to ionizing radiation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In selected children, asymptomatic renal stones smaller than 5 mm are commonly managed conservatively with imaging surveillance, hydration counselling, and metabolic evaluation [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdequate hydration is central to stone prevention because concentrated urine contributes to lithogenesis [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In routine practice, urine concentration is typically assessed by urine osmolality or specific gravity [\u003cspan additionalcitationids=\"CR7\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In infants, however, repeated urine assessment between imaging visits is difficult. First-morning samples are not always feasible, 24-hour urine collection is rarely practical, and laboratory testing may not be readily available in outpatient settings.\u003c/p\u003e \u003cp\u003eHandheld TDS meters generate rapid conductivity-based readings from small urine volumes. Such devices may appear attractive for repeated outpatient measurement in diapered infants, but important interpretive limitations remain. Conductivity-derived TDS is not equivalent to urine osmolality and should not be regarded as a validated hydration biomarker. Rather, it represents a device-derived signal influenced by ionic composition, urine matrix characteristics, and meter-specific conversion methods [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In infant urine, where feeding patterns, recent intake, and urinary composition may vary substantially, the biological meaning of a handheld TDS reading is uncertain.\u003c/p\u003e \u003cp\u003eTo our knowledge, no published study has specifically examined handheld urine TDS values in infants with ultrasound-detected renal stones smaller than 5 mm. We therefore undertook this pilot study to determine whether mean handheld urine TDS differs between infants with and without ultrasound-detected renal stones smaller than 5 mm. We also sought to generate preliminary data that could inform future analytical validation studies.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and setting\u003c/h2\u003e \u003cp\u003eThis was a prospective pilot comparative study conducted in a tertiary paediatric urology outpatient clinic between January and December 2025. Urine TDS measurements and ultrasound-based stone status were assessed during the same study period. The study was designed to examine association rather than causality, prediction, or diagnostic performance.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eCases were infants younger than 24 months with asymptomatic renal stones smaller than 5 mm identified on ultrasonography. Controls were stone-negative infants recruited consecutively from the same outpatient ultrasonography population during the same period in order to reduce referral-setting differences between groups.\u003c/p\u003e \u003cp\u003eCases were excluded if they had symptomatic stone episodes, obstructive stones, urinary tract infection at the time of sampling, acute systemic illness, ongoing treatment for acute metabolic or electrolyte disorders, visible sample contamination, or incomplete data. Controls were excluded if they had previous urolithiasis, current urinary tract infection, fever, acute gastroenteritis with vomiting or diarrhoea, chronic kidney disease, major congenital urinary anomalies, diuretic use, visible sample contamination, incomplete data, or conditions known to affect fluid or electrolyte balance. No individual matching was performed. Age and sex were prespecified covariates.\u003c/p\u003e\n\u003ch3\u003eUltrasonography\u003c/h3\u003e\n\u003cp\u003eRenal and bladder ultrasonography was performed for routine clinical indications and interpreted by a paediatric radiologist blinded to urine TDS results. Stone status was based on the final radiology report. Cases were defined as infants with a renal stone or calculus smaller than 5 mm on ultrasonography. Controls had no renal stones reported.\u003c/p\u003e \u003cp\u003eBecause ultrasound may misclassify very small calculi, particularly lesions smaller than 5 mm, stone status was treated as an imaging-based clinical classification rather than a reference standard.\u003c/p\u003e\n\u003ch3\u003eUrine sampling and TDS measurement\u003c/h3\u003e\n\u003cp\u003eBecause first-morning and 24-hour urine collection are often impractical in infants, non-first-morning daytime spot urine samples were used. Samples were collected during clinic hours (09:00\u0026ndash;15:00) using paediatric urine collection bags on three non-consecutive days within a 10-day period. Mean TDS values were calculated from these repeated measurements to reduce the influence of short-term within-subject variation.\u003c/p\u003e \u003cp\u003e Feeding patterns included breast milk, formula feeding, and complementary foods according to age. Dietary composition, feeding timing, and intake immediately before sampling were not standardized.\u003c/p\u003e \u003cp\u003eUrine was transferred to clean single-use containers after collection, and samples with visible stool contamination were excluded. TDS was measured using a handheld conductivity-based meter (OHAUS ST 20 T-B) with automatic temperature compensation. The device was calibrated daily according to the manufacturer\u0026rsquo;s instructions. Each sample was measured twice consecutively, and the mean of the two readings was used for analysis.\u003c/p\u003e \u003cp\u003eResults were recorded in ppm as device-based conductivity values. These readings were not treated as equivalents of urine osmolality or direct biochemical total solute concentration.\u003c/p\u003e \u003cp\u003eUrine specific gravity was obtained by routine dipstick urinalysis at the time of clinical evaluation and was used descriptively. Formal comparison with urine osmolality or refractometric specific gravity was not performed.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was renal stone status on ultrasonography (present or absent). The primary explanatory variable was mean urine TDS in ppm, averaged from three non-consecutive daytime measurements.\u003c/p\u003e \u003cp\u003eThe study did not evaluate hydration status against a biochemical reference standard and did not assess longitudinal outcomes such as stone growth, persistence, recurrence, or response to hydration counselling.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eNo formal a priori sample size calculation was performed because of the exploratory pilot design. Sample size was determined by the number of eligible infants during the study period.\u003c/p\u003e \u003cp\u003eContinuous variables were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median with interquartile range, and categorical variables as counts and percentages. Between-group comparisons were performed using Welch\u0026rsquo;s t-test for continuous variables and the chi-square test or Fisher\u0026rsquo;s exact test for categorical variables. Effect size was expressed as Cohen\u0026rsquo;s d.\u003c/p\u003e \u003cp\u003eROC analysis was used descriptively to assess sample-level separation of TDS values by stone status. The area under the curve (AUC) with 95% confidence interval was reported. Because of the pilot design, balanced sampling, and uncertainty regarding the biological meaning of TDS, ROC findings were not used to derive clinically applicable thresholds.\u003c/p\u003e \u003cp\u003eMultivariable logistic regression was used to model stone presence with mean TDS per 100 ppm increase, age in months, and sex as prespecified covariates. TDS was specified a priori as a linear term per 100 ppm increase in order to preserve model simplicity in this pilot dataset. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were reported. Model calibration was assessed with the Hosmer\u0026ndash;Lemeshow goodness-of-fit test.\u003c/p\u003e \u003cp\u003eA sensitivity analysis excluding the highest decile of TDS values was performed to assess whether extreme readings disproportionately influenced the association. A two-sided p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Analyses were performed using IBM SPSS Statistics version 29.0.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eEthics\u003c/h3\u003e\n\u003cp\u003e \u003cstrong\u003eEthics approval\u003c/strong\u003e \u003cp\u003e was obtained from the local institutional ethics committee (approval number: 226/2025) in accordance with the Declaration of Helsinki. Written informed consent for participation and publication of anonymized data was obtained from the parents or legal guardians of all participants. Clinical trial number: not applicable.\u003c/p\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eParticipant characteristics\u003c/h2\u003e\n \u003cp\u003eA total of 74 infants were included in the final analysis: 37 in the stone group and 37 in the control group. Age and sex distributions were similar between groups (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eMean urinary TDS was higher in infants with stones than in controls (480.6\u0026thinsp;\u0026plusmn;\u0026thinsp;171.6 ppm vs 306.8\u0026thinsp;\u0026plusmn;\u0026thinsp;67.9 ppm; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), with a large effect size (Cohen\u0026rsquo;s d\u0026thinsp;\u0026asymp;\u0026thinsp;1.3). Urine dipstick specific gravity values were similar between groups.\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDemographic characteristics and urine total dissolved solids values in infants with ultrasound-detected renal stones smaller than 5 mm and stone-negative controls.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eStone group (n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c3\"\u003e\n \u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c4\"\u003e\n \u003cp\u003ep value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eAge (months), median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e15.3 (11.2\u0026ndash;20.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e16.4 (10.5\u0026ndash;19.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eMale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e21 (56.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e24 (64.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eFemale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e16 (43.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e13 (35.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eTDS (ppm), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e480.6\u0026thinsp;\u0026plusmn;\u0026thinsp;171.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e306.8\u0026thinsp;\u0026plusmn;\u0026thinsp;67.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eTDS (ppm), median (min\u0026ndash;max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e489.0 (169\u0026ndash;762)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e297.1 (134\u0026ndash;442)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eUrine specific gravity, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e1.016 (1.015\u0026ndash;1.018)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\n \u003cp\u003e1.015 (1.014\u0026ndash;1.017)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003c/p\u003e\n \u003cp\u003eBaseline demographic characteristics and urine total dissolved solids (TDS) measurements of study participants according to renal stone status. Continuous variables are presented as mean \u0026plusmn; standard deviation or median (interquartile range), and categorical variables as number (percentage).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e TDS, total dissolved solids; IQR, interquartile range; SD, standard deviation.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cp\u003e\u003cstrong\u003eUrinalysis and metabolic findings in the stone group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eWithin the stone group, routine urinalysis and available spot urinary metabolic findings were heterogeneous. Microscopic hematuria and pyuria were present in a subset of infants, whereas proteinuria and crystalluria were less common. Hyperuricosuria and hypercalciuria were among the most frequent spot urinary metabolic abnormalities. No detectable metabolic abnormality was identified in 11 of 37 infants (Table 2).\u003c/p\u003e\n \u003cp\u003eComparable structured metabolic data were not available for controls; therefore, these findings are descriptive only and cannot be used to determine whether group differences in TDS reflect stone status itself, differences in urine composition, or both.\u003c/p\u003e\u0026nbsp;\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eUrinalysis and spot urinary metabolic findings among infants with ultrasound-detected renal stones smaller than 5 mm.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"2\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colname=\"c2\"\u003e\n \u003cp\u003eStone group (n\u0026thinsp;=\u0026thinsp;37)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eUrine specific gravity, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e1.016 (1.015\u0026ndash;1.018)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eUrine pH, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e6.0 (5.5\u0026ndash;6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eMicroscopic hematuria, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e11 (29.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003ePyuria, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e9 (24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eProteinuria, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e4 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eCrystalluria, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e3 (8.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eHypercalciuria, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e12/37 (32.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eHyperoxaluria, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e5/37 (13.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eHypocitraturia, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e4/37 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eHyperuricosuria, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e16/37 (43.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eHypomagnesuria, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e9/37 (24.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eCystinuria, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e1/37 (2.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colname=\"c1\"\u003e\n \u003cp\u003eNo detected metabolic abnormality, n/N (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\n \u003cp\u003e11/37 (29.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003eDescriptive urinalysis and spot urinary metabolic characteristics of infants in the stone group. Continuous variables are presented as median (interquartile range), and categorical variables as number/total number (percentage), where applicable. Metabolic findings are reported descriptively and were not compared statistically with controls.\u003cbr\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e IQR, interquartile range.\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cstrong\u003eROC analysis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eROC analysis showed moderate sample-level separation of mean TDS values according to stone status, with an AUC of 0.80 (95% CI 0.696\u0026ndash;0.900). Given the pilot design, balanced sampling, and uncertainty about what TDS captures biologically, this finding was interpreted descriptively only.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariable analysis\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eIn multivariable logistic regression adjusted for age and sex, mean TDS remained associated with stone presence. Each 100 ppm increase in TDS was associated with higher odds of stone detection (adjusted OR 2.92; 95% CI 1.73\u0026ndash;4.93; p \u0026lt; 0.0001). The Hosmer\u0026ndash;Lemeshow test showed no evidence of poor model fit (p = 0.64).\u003c/p\u003e\n \u003cp\u003eSensitivity analysis excluding the highest decile of TDS values produced similar estimates, suggesting that the observed association was not driven only by extreme measurements.\u003c/p\u003e\n \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis pilot study found that infants with ultrasound-detected renal stones smaller than 5 mm had higher handheld urine TDS values than stone-negative controls. The association remained statistically significant after adjustment for age and sex. At face value, this suggests that stone status was associated with a higher device-derived conductivity signal in the sampled urine specimens.\u003c/p\u003e\n\u003cp\u003eThe interpretation of that association, however, is limited. Handheld urine TDS is not a validated equivalent of urine osmolality, and in this study it cannot be assumed to represent urine concentration alone. Conductivity-based measurements are influenced by ionic composition and by device-specific conversion methods [9,10]. In the present setting, higher TDS values may reflect more concentrated urine, differences in urinary solute composition, or a combination of both.\u003c/p\u003e\n\u003cp\u003eThat distinction is important because stone formation in infancy is multifactorial. A higher TDS value in the stone group does not mean that the device captured a specific lithogenic mechanism, nor does it establish that TDS is measuring hydration status. It is also plausible that urinary abnormalities more common in stone-forming infants, including differences in calcium, uric acid, or other ionic constituents, contributed to the higher readings.\u003c/p\u003e\n\u003cp\u003eThis concern is reinforced by the descriptive metabolic findings. Hyperuricosuria and hypercalciuria were relatively common in the stone group, but comparable structured metabolic data were not available for controls. As a result, the study cannot distinguish whether the observed difference in TDS primarily reflects stone status, differences in urine composition, differences in urine concentration, or overlap among these factors.\u003c/p\u003e\n\u003cp\u003eA related point is the absence of a clear between-group difference in dipstick urine specific gravity. Because strip-based specific gravity has known analytical limitations [11], this does not invalidate the TDS finding. However, it does caution against treating TDS as a straightforward surrogate of conventional concentration measures. The discordance between these two urine measures supports the view that they may be capturing different physical or analytical properties of the specimen.\u003c/p\u003e\n\u003cp\u003eThe study also has important design limitations. Ultrasound-based classification of very small renal stones is imperfect and may have introduced outcome misclassification. Repeated spot sampling was used to reduce short-term variation, but within-subject reproducibility of TDS was not formally assessed. Urine collection by paediatric bag, daytime sampling, and non-standardized feeding patterns introduced additional biological and pre-analytical variability. Residual confounding from recent fluid intake, feeding interval, ambient temperature, and unmeasured urinary composition was likely. The multivariable model adjusted only for age and sex, which preserved parsimony but does not eliminate broader confounding.\u003c/p\u003e\n\u003cp\u003eThese limitations place the findings firmly in the exploratory domain. The study does not support clinical use of handheld TDS as a diagnostic test, a hydration biomarker, or a substitute for urine osmolality or refractometric specific gravity. Its main contribution is narrower: it shows that a handheld conductivity-derived urine signal differed between stone-positive and stone-negative infants in this pilot cohort.\u003c/p\u003e\n\u003cp\u003eThat limited finding may still be useful. In infants, repeated standard urine testing is often difficult, and simple device-based measurements are appealing for practical reasons. Before any clinical role can be considered, however, future studies need to establish what handheld TDS is actually measuring in urine. Direct analytical comparison with urine osmolality, refractometric specific gravity, and urinary solute composition in the same specimens is essential. Only after such validation would it be reasonable to examine whether serial TDS measurements have longitudinal clinical relevance for stone persistence, progression, recurrence, or response to hydration counselling.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this prospective pilot comparative study, handheld urine TDS values were higher in infants with ultrasound-detected renal stones smaller than 5 mm than in stone-negative controls. These findings support an association between stone status and a device-derived conductivity signal, but they do not establish that TDS reflects urine concentration alone or that it has diagnostic value. Further analytical validation and longitudinal studies are required before any clinical application can be considered.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eAUC\u003c/strong\u003e: Area under the curve\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eCI\u003c/strong\u003e: Confidence interval\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eOR\u003c/strong\u003e: Odds ratio\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eROC\u003c/strong\u003e: Receiver operating characteristic\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eSD\u003c/strong\u003e: Standard deviation\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eTDS\u003c/strong\u003e: Total dissolved solids\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the patients and their families for their participation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cul type=\"disc\"\u003e\n \u003cli\u003e\u003cstrong\u003eConceptualization:\u003c/strong\u003e YAB\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eMethodology:\u003c/strong\u003e YAB, HD\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eData collection:\u003c/strong\u003e YAB\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eFormal analysis:\u003c/strong\u003e YAB\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eWriting \u0026ndash; original draft:\u003c/strong\u003e YAB\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eWriting \u0026ndash; review and editing:\u003c/strong\u003e HD\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003eAll authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval was obtained from Hatay Education and Research Hospital Ethics Committee (approval number: 226/2025). Written informed consent for participation was obtained from the parents or legal guardians of all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eClinical trial number: not applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication of anonymized data was obtained from the parents or legal guardians of all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests. They have no financial relationship with the manufacturer of the device used in this study.\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests and no financial, commercial, or personal relationship with the manufacturer or distributor of the handheld TDS device used in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHernandez J, Ellison JS, Lendvay TS. Current trends, evaluation, and management of pediatric nephrolithiasis. JAMA Pediatr. 2015;169(10):964\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrivas N, Thomas K, Drake T, Donaldson JF, Neisius A, Petř\u0026iacute;k A, et al. Imaging modalities and treatment of paediatric upper tract urolithiasis: a systematic review and update on behalf of the EAU Urolithiasis Guidelines Panel. J Pediatr Urol. 2020;16(3):220\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLombardo R, Tzelves L, Geraghty R, Davis NF, Neisius A, Petř\u0026iacute;k A, et al. Follow-up of urolithiasis patients after treatment: an algorithm from the EAU Urolithiasis Panel. World J Urol. 2024;42:1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePearle MS, Goldfarb DS, Assimos DG, Curhan GC, Denu-Ciocca CJ, Matlaga BR, et al. Medical management of kidney stones: AUA guideline. J Urol. 2014;192(2):316\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKanno T, Takahashi T, Ito K, Okada T, Higashi Y, Yamada H. The natural history of asymptomatic renal stones\u0026thinsp;\u0026le;\u0026thinsp;5 mm: comparison with \u0026ge;\u0026thinsp;5 mm. J Endourol. 2020;34(11):1188\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSkolarikos A, Straub M, Knoll T, Sarica K, Seitz C, Petř\u0026iacute;k A, T\u0026uuml;rk C. Metabolic evaluation and recurrence prevention for urinary stone patients: EAU guidelines. Eur Urol. 2015;67(4):750\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eInjeyan M, Bidault V, Bacchetta J, Bertholet-Thomas A. Hydration and nephrolithiasis in pediatric populations: specificities and current recommendations. Nutrients. 2023;15:728.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKang HW, Seo SP, Ha YS, Kim WT, Kim YJ, Yun SJ, et al. Twenty-four-hour urine osmolality as a representative index of adequate hydration and a predictor of recurrence in patients with urolithiasis. Int Urol Nephrol. 2019;51:1129\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eManoni F, Fornasiero L, Ercolin M, Tinello A, Ferrian M, Valverde S, et al. Laboratory diagnosis of renal failure: urine conductivity and tubular function. Minerva Urol Nefrol. 2009;61(1):17\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFazil Marickar YM. Electrical conductivity and total dissolved solids in urine. Urol Res. 2010;38:233\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eD\u0026ouml;rner K, Campos H, B\u0026ouml;rnsen H. Evaluation of the SG test strip. J Clin Chem Clin Biochem. 1984;22:419\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMao W, Zhang H, Xu Z, Geng J, Zhang Z, Wu J, et al. Relationship between urine specific gravity and the prevalence rate of kidney stone. Transl Androl Urol. 2020;10:184\u0026ndash;94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeerapen P, Thongboonkerd V. Kidney stone prevention. Adv Nutr. 2023;14(3):555\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"Infant, nephrolithiasis, renal stones, ultrasonography, urine conductivity, hydration, total dissolved solids","lastPublishedDoi":"10.21203/rs.3.rs-9405719/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9405719/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInfants with asymptomatic renal stones smaller than 5 mm are often managed conservatively with ultrasonographic follow-up and hydration counselling. In diapered children, repeated outpatient urine assessment is difficult because first-morning samples, 24-hour urine collections, and laboratory osmolality testing are often impractical. Handheld total dissolved solids (TDS) meters provide rapid conductivity-based readings from small urine volumes, but the biological meaning of these readings in infant urine is uncertain and they are not validated equivalents of established urine concentration measures. This pilot study investigated whether handheld urine TDS values are associated with ultrasound-detected renal stones smaller than 5 mm in infants younger than 24 months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis prospective pilot comparative study included infants younger than 24 months with and without ultrasound-detected renal stones smaller than 5 mm. Non-first-morning daytime spot urine samples were collected on three non-consecutive days within a 10-day period, and mean TDS values were calculated. Receiver operating characteristic (ROC) analysis was used descriptively to assess sample-level separation, and multivariable logistic regression adjusted for age and sex was used to examine association.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSeventy-four infants were included: 37 cases and 37 controls. Mean urine TDS was higher in infants with stones than in controls (480.6 ± 171.6 vs 306.8 ± 67.9 ppm; p \u0026lt; 0.01), corresponding to a large effect size (Cohen’s d ≈ 1.3). ROC analysis showed an area under the curve of 0.80 (95% CI 0.696–0.900). In multivariable analysis adjusted for age and sex, each 100 ppm increase in TDS was associated with higher odds of stone presence (adjusted OR 2.92; 95% CI 1.73–4.93; p \u0026lt; 0.0001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this pilot cohort, handheld urine TDS values were higher in infants with ultrasound-detected renal stones smaller than 5 mm than in stone-negative controls. These findings indicate an association between stone status and a device-derived conductivity signal, but they do not establish diagnostic validity or confirm that TDS reflects urine concentration alone. Direct analytical validation and longitudinal studies are needed before any clinical role can be considered.\u003c/p\u003e","manuscriptTitle":"Handheld urine total dissolved solids and ultrasound-detected renal stones smaller than 5 mm in infants: a prospective pilot comparative study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-23 09:36:28","doi":"10.21203/rs.3.rs-9405719/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":"0c82a6a7-1a9c-4697-b483-e2aa572b707a","owner":[],"postedDate":"April 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-04-23T09:36:28+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-23 09:36:28","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9405719","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9405719","identity":"rs-9405719","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}