{"paper_id":"2bc5ef53-ed1d-4892-8cac-ab675f2c90c7","body_text":"Association of Serum Vitamin D Levels with Urinary Tract Infections in Adult Patients: A Cross-Sectional Prospective 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 Association of Serum Vitamin D Levels with Urinary Tract Infections in Adult Patients: A Cross-Sectional Prospective Study Krittin Naravejsakul, Mallika Khwanmuang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7111661/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 Urinary tract infections (UTIs) pose a significant global health burden. While vitamin D plays a known role in immune modulation, its association with UTI risk in adult populations remains underexplored. Objectives To investigate the association between serum vitamin D levels and the risk of upper and lower UTIs in adults, and to evaluate the relative risk contributions of comorbid conditions and modifiable risk factors. Methods We conducted a prospective case-control study involving 404 adult participants (203 controls, 73 with upper UTI, 128 with lower UTI). Serum 25(OH)D levels were categorized into deficient, insufficient, and sufficient. Logistic regression was used to calculate adjusted odds ratios (aOR). Absolute Risk Difference (ARD) and Number Needed to Harm (NNH) were computed. Results Vitamin D deficiency was significantly associated with both upper UTIs (aOR = 1.85; ARD = 12.9%; NNH = 8) and lower UTIs (aOR = 1.65; ARD = 10.3%; NNH = 10) compared to controls. Additional risk factors included diabetes mellitus (aOR = 1.92), recent antibiotic use (aOR = 2.77), and Foley catheter presence (aOR = 2.34). A causal hypothesis model supports biologic plausibility through impaired antimicrobial defense and barrier integrity. Conclusion Vitamin D deficiency is an independent risk factor for adult UTIs. Routine screening and targeted supplementation may provide a cost-effective adjunct to UTI prevention, particularly among high-risk populations. Future longitudinal studies and randomized controlled trials are warranted to confirm causality and guide implementation. vitamin D deficiency urinary tract infection case-control study antimicrobial peptides innate immunity adult patients Figures Figure 1 Introduction Urinary tract infections (UTIs) represent a pervasive global health challenge, affecting millions annually and imposing substantial healthcare burdens [ 1 ]. Ranging from uncomplicated cystitis to severe pyelonephritis, UTIs can lead to life-threatening complications such as sepsis [ 3 ]. The escalating prevalence of antibiotic resistance among uropathogenic bacteria, particularly Escherichia coli , underscores the urgent need for innovative preventive and therapeutic strategies [ 4 ]. The pathogenesis of UTIs involves a complex interplay between bacterial virulence and host defense mechanisms. The urinary tract employs multiple protective layers, including mechanical flushing, antimicrobial properties of urine, and innate immune responses of the urothelium [ 5 ]. The integrity of the epithelial barrier and the production of antimicrobial peptides are critical components of this defense system [ 6 ]. Vitamin D, traditionally recognized for its role in calcium homeostasis, has emerged as a pivotal regulator of both innate and adaptive immunity [ 7 ]. The widespread presence of vitamin D receptors (VDR) and 1α-hydroxylase enzyme in various extrarenal tissues, including the urogenital tract, highlights its extensive immunomodulatory functions [ 8 ]. Vitamin D deficiency, defined as serum 25-hydroxyvitamin D levels below 20 ng/mL (50 nmol/L), is a global pandemic affecting approximately one billion individuals and is linked to heightened susceptibility to diverse infectious diseases [ 9 ]. The immunoprotective mechanisms of vitamin D are highly relevant to urinary tract defense. Upon conversion to its active form, 1,25-dihydroxyvitamin D3, vitamin D induces the expression of antimicrobial peptides, notably cathelicidin (LL-37) and β-defensins [ 10 ]. Cathelicidin exhibits broad-spectrum antimicrobial activity against uropathogens, providing a crucial first line of defense [ 11 ]. Furthermore, vitamin D enhances epithelial tight junctions, strengthening the physical barrier against bacterial invasion [ 12 ]. It also modulates adaptive immune responses by promoting regulatory T-cell function and mitigating excessive inflammation [ 13 ]. Experimental studies have demonstrated that vitamin D deficiency impairs antimicrobial peptide production in the urinary tract, creating a more permissive environment for bacterial colonization [ 14 ]. Uropathogenic E. coli can actively downregulate epithelial barrier proteins, an effect potentially counteracted by adequate vitamin D status [ 15 ]. These mechanistic insights provide a strong biological foundation for the observed clinical associations between vitamin D deficiency and increased UTI risk. Clinical evidence linking vitamin D status to UTI susceptibility is growing, albeit with some inconsistencies. A systematic review and meta-analysis by Deng et al. found a significant association between vitamin D insufficiency and increased UTI risk (pooled OR = 3.01, 95% CI = 2.31–3.91) [ 16 ]. However, this meta-analysis predominantly included pediatric cohorts, with limited data on adult populations where UTI epidemiology and risk factors may differ. Studies in adults, particularly case-control designs, are crucial for robust risk factor assessment. Several studies have specifically examined the relationship between vitamin D and recurrent UTIs. Nseir et al. reported an independent association between vitamin D deficiency and recurrent UTIs in premenopausal women [ 17 ]. Similarly, studies in immunocompromised populations, such as renal transplant recipients, have identified vitamin D deficiency as an independent risk factor for post-transplant UTIs [ 18 ]. These findings suggest that vitamin D's protective effects may be particularly pronounced in vulnerable populations. Despite these insights, several knowledge gaps persist. First, data on adult cohorts, where UTI epidemiology and risk factors may differ from pediatric populations, remain limited. Second, few studies have systematically compared the association between vitamin D deficiency and distinct UTI types (e.g., upper vs. lower), which may have differing pathophysiological mechanisms. Third, the comprehensive evaluation of confounding factors, such as diabetes mellitus, immunosuppression, and recent healthcare exposures, in the context of vitamin D status is often lacking. The clinical implications of establishing a clear association between vitamin D deficiency and UTI risk are substantial. If vitamin D deficiency is a modifiable risk factor, routine screening and targeted supplementation could offer cost-effective interventions for UTI prevention, particularly in high-risk groups. This approach could reduce antibiotic consumption, decrease healthcare utilization, and improve patient quality of life, while also addressing the critical issue of antimicrobial resistance. Given these considerations, we conducted a comprehensive case-control study to investigate the association between serum vitamin D levels and UTI occurrence in adult patients. Our primary objective was to quantify the relationship between vitamin D deficiency and overall UTI risk. Secondary objectives included comparing this association between upper and lower UTIs and identifying additional risk factors that may interact with vitamin D status. We hypothesized that vitamin D deficiency would be significantly associated with increased UTI risk in adult patients, with potentially stronger associations observed in upper UTIs due to their more severe inflammatory response and systemic involvement. Methods Study Design and Setting This case-control study was conducted at a tertiary care medical center to investigate the association between serum vitamin D levels and urinary tract infections in adult patients. The study design and reporting adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for case-control studies [ 19 ]. The study protocol received approval from the institutional review board, and all participants provided written informed consent prior to enrollment. Data collection was performed prospectively over a 12-month period from January 2023 to December 2023. Participants and Selection Criteria The study population comprised adult patients aged 18 years and older presenting to our institution during the study period. Participants were stratified into three groups: controls (non-UTI patients), upper UTI cases, and lower UTI cases. Sample size calculations, based on a two-sided alpha of 0.05, 80% power, and an expected odds ratio of 2.0 for the association between vitamin D deficiency and UTI (derived from existing literature), indicated a minimum requirement of 150 participants per group. We exceeded this target to ensure adequate statistical power for planned subgroup analyses. Case Definition and Classification UTI cases were defined by the presence of clinical symptoms suggestive of urinary tract infection coupled with laboratory confirmation. Upper UTI (pyelonephritis) was diagnosed in patients presenting with fever (≥ 38.0°C), flank pain, costovertebral angle tenderness, and systemic symptoms (e.g., nausea, vomiting, malaise), in conjunction with positive urine culture results. Lower UTI (cystitis) was diagnosed in patients presenting with dysuria, urinary frequency, urgency, suprapubic pain, or hematuria, without systemic symptoms, also confirmed by positive urine culture. Microbiological confirmation required either: (1) ≥ 10^5 colony-forming units (CFU) per milliliter of a single uropathogenic organism in a clean-catch midstream urine specimen, or (2) ≥ 10^4 CFU/mL of a single uropathogen in the presence of compatible clinical symptoms. Urine specimens were processed within two hours of collection using standard microbiological techniques. Bacterial identification and antimicrobial susceptibility testing were performed using automated systems (VITEK 2, bioMérieux, France). Control Selection Control participants were recruited from patients attending outpatient clinics for routine health maintenance, preoperative evaluations, or non-infectious medical conditions. Controls were required to be free of current urinary symptoms, have no history of UTI within the preceding three months, and exhibit negative urine analysis (absence of pyuria, defined as < 10 white blood cells per high-power field, and absence of bacteriuria). Controls were frequency-matched to cases by age group (18–30, 31–50, 51–70, > 70 years) and gender where feasible. Inclusion Criteria : For all participants: age ≥ 18 years, ability to provide informed consent, and availability of a serum sample for vitamin D measurement. For UTI cases: clinical presentation consistent with UTI and microbiological confirmation as defined above. For controls: absence of urinary symptoms and negative urine analysis. Exclusion Criteria : Participants were excluded if they had: (1) chronic kidney disease (estimated glomerular filtration rate < 30 mL/min/1.73m²), (2) active immunosuppressive therapy (including corticosteroids, chemotherapy, or immunosuppressive medications), (3) current vitamin D supplementation exceeding 1000 IU daily, (4) pregnancy or lactation, (5) active malignancy, (6) chronic inflammatory conditions (e.g., inflammatory bowel disease, rheumatoid arthritis), (7) recent hospitalization within 30 days, or (8) inability to provide a reliable clinical history. Data Collection and Variables Demographic and clinical data were collected using standardized case report forms. Trained research personnel conducted structured interviews and reviewed medical records to ensure data completeness and accuracy. The following variables were systematically collected for all participants: Demographic Variables Age, gender, race/ethnicity, body mass index (BMI), educational level, and socioeconomic status indicators were recorded. Seasonal variation was accounted for by documenting the month of enrollment, given the known seasonal fluctuations in vitamin D levels in temperate climates. Clinical Presentation For UTI cases, detailed symptom assessment included onset, duration, and severity of urinary symptoms, presence of fever, flank pain, suprapubic pain, dysuria, frequency, urgency, hematuria, and systemic symptoms. Pain severity was assessed using a 10-point visual analog scale. For controls, any urinary symptoms within the preceding month were documented and served as additional exclusion criteria if present Risk Factor Assessment : Comprehensive evaluation of established UTI risk factors was performed, including: diabetes mellitus (type 1 or 2, with documentation of glycemic control), recent antibiotic use (within 30 days), presence of indwelling urinary catheter (Foley catheter), recent urological procedures (within 90 days), history of recurrent UTIs (≥ 3 episodes in the preceding 12 months), sexual activity patterns, contraceptive use, post-menopausal status in women, benign prostatic hyperplasia in men, and any anatomical abnormalities of the urinary tract. Comorbidity Documentation Systematic assessment of comorbid conditions included hypertension, cardiovascular disease, chronic obstructive pulmonary disease, liver disease, autoimmune disorders, and any condition requiring chronic medication use. The Charlson Comorbidity Index was calculated for each participant to provide a standardized measure of overall health status. Laboratory Methods Urine Collection and Analysis Urine specimens were collected using the clean-catch midstream technique after appropriate patient education. For patients unable to provide clean-catch specimens, catheterized samples were obtained using sterile technique. Urine analysis was performed within two hours of collection using automated microscopy (UF-1000i, Sysmex Corporation, Japan). Parameters assessed included specific gravity, protein, glucose, ketones, blood, leukocyte esterase, nitrites, and microscopic examination for white blood cells, red blood cells, bacteria, and epithelial cells. Serum Vitamin D Measurement Blood samples for vitamin D analysis were collected in serum separator tubes and processed within four hours. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured using a chemiluminescent microparticle immunoassay (ARCHITECT i2000SR, Abbott Laboratories, USA). This assay demonstrates excellent analytical performance with inter-assay coefficient of variation < 10% and intra-assay coefficient of variation < 5%. The assay measures both 25(OH)D2 and 25(OH)D3, providing total 25(OH)D concentration. Vitamin D status was classified according to the Endocrine Society Clinical Practice Guidelines: deficient (< 20 ng/mL or < 50 nmol/L), insufficient (20-29.9 ng/mL or 50-74.9 nmol/L), and sufficient (≥ 30 ng/mL or ≥ 75 nmol/L) [ 20 ]. These thresholds are widely accepted in clinical practice and have been validated in multiple populations for assessment of vitamin D adequacy. Additional Laboratory Investigations Complete blood count with differential was performed using automated hematology analyzers (XN-1000, Sysmex Corporation, Japan). Serum biochemistry panel included measurement of creatinine, blood urea nitrogen, glucose, electrolytes (sodium, potassium, chloride), and liver function tests using automated chemistry analyzers (ARCHITECT c16000, Abbott Laboratories, USA). Estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Statistical Analysis Statistical analyses were performed using SPSS version 28.0 (IBM Corporation, Armonk, NY, USA) and R version 4.3.0 (R Foundation for Statistical Computing, Vienna, Austria). Descriptive statistics were calculated for all variables, with continuous variables presented as means ± standard deviations for normally distributed data or medians with interquartile ranges for non-normally distributed data. Categorical variables were presented as frequencies and percentages. Univariate Analysis Comparisons between groups were performed using appropriate statistical tests based on data distribution and variable type. One-way analysis of variance (ANOVA) was used for continuous variables with normal distribution, with post-hoc pairwise comparisons performed using Tukey's honestly significant difference test when overall ANOVA was significant. For non-normally distributed continuous variables, the Kruskal-Wallis test was employed with Dunn's test for post-hoc comparisons. Chi-square tests were used for categorical variables, with Fisher's exact test applied when expected cell counts were less than five. Effect Size Calculations Cohen's d was calculated to assess the magnitude of differences in continuous variables between groups, with values of 0.2, 0.5, and 0.8 representing small, medium, and large effect sizes, respectively. For categorical variables, Cramér's V was calculated to assess the strength of association. Primary Analysis : The primary outcome was the association between vitamin D deficiency (< 20 ng/mL) and UTI occurrence. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using logistic regression analysis. Separate analyses were performed comparing: (1) all UTI cases versus controls, (2) upper UTI cases versus controls, (3) lower UTI cases versus controls, and (4) upper UTI versus lower UTI cases. Secondary Analyses Secondary analyses examined vitamin D as a continuous variable and as a three-category variable (deficient, insufficient, sufficient). Linear regression was used to assess the relationship between continuous vitamin D levels and UTI risk after log-transformation to achieve normal distribution. Ordinal logistic regression was employed to examine trends across vitamin D categories. Confounding and Effect Modification Potential confounding variables were identified a priori based on literature review and clinical knowledge. These included age, gender, diabetes mellitus, immunocompromised status, recent antibiotic use, presence of urinary catheter, and recent urological procedures. Multivariable logistic regression models were constructed to adjust for potential confounders, with variables included if they were associated with both the exposure (vitamin D status) and outcome (UTI) at p < 0.20 in univariate analysis. Effect modification was assessed by including interaction terms in the logistic regression models and testing for statistical significance. Stratified analyses were performed when significant interactions were identified. Sample Size and Power Post-hoc power calculations were performed to ensure adequate statistical power for detecting clinically meaningful associations. With the achieved sample size of 404 participants, the study had > 90% power to detect an odds ratio of 1.8 or greater for the association between vitamin D deficiency and UTI, assuming a vitamin D deficiency prevalence of 25% in controls and alpha level of 0.05. Missing Data Missing data patterns were assessed and found to be minimal (< 5% for any variable). Complete case analysis was performed for the primary analysis, with sensitivity analyses conducted using multiple imputation for missing values to assess the robustness of findings. All statistical tests were two-sided, and p-values < 0.05 were considered statistically significant. Bonferroni correction was applied for multiple comparisons when appropriate to control for type I error inflation. Results Study Population Characteristics A total of 404 adult participants were enrolled in this case-control study, comprising 203 controls without UTI, 73 patients with upper UTI (pyelonephritis), and 128 patients with lower UTI (cystitis). The participant flow and selection process are illustrated in Fig. 1. The overall response rate was 94.2%, with minimal missing data across all measured variables (< 3% for any single variable). Demographic Characteristics The demographic characteristics of the study population are presented in Table 1 . The mean age differed significantly across groups (ANOVA p = 0.0259), with controls having a mean age of 59.9 ± 22.0 years, upper UTI patients 61.7 ± 23.1 years, and lower UTI patients 54.0 ± 23.2 years. Post-hoc pairwise comparisons revealed that lower UTI patients were significantly younger than both controls (p = 0.0199) and upper UTI patients (p = 0.0240), while no significant age difference was observed between controls and upper UTI patients (p = 0.5553). Table 1 Baseline Characteristics of Study Participants Characteristic Controls (n = 203) Upper UTI (n = 73) Lower UTI (n = 128) p-value Demographics Age (years), mean ± SD 59.9 ± 22.0 61.7 ± 23.1 54.0 ± 23.2 0.0259* Female gender, n (%) 143 (70.4) 58 (79.5) 97 (75.8) 0.4919 BMI (kg/m²), mean ± SD 26.8 ± 4.2 27.1 ± 4.8 26.5 ± 4.1 0.6847 Risk Factors Diabetes mellitus, n (%) 72 (35.5) 36 (49.3) 38 (29.7) 0.0198* Immunocompromised, n (%) 35 (17.2) 7 (9.6) 7 (5.5) 0.0046* Recent antibiotic use, n (%) 68 (33.5) 49 (67.1) 42 (32.8) < 0.0001* Foley catheter, n (%) 41 (20.2) 33 (45.2) 32 (25.0) 0.0002* Urological procedure, n (%) 24 (11.8) 23 (31.5) 25 (19.5) 0.0007* *Statistically significant (p < 0.05) Gender distribution showed a predominance of female participants across all groups, consistent with the known epidemiology of UTIs. Female participants comprised 70.4% of controls (143/203), 79.5% of upper UTI patients (58/73), and 75.8% of lower UTI patients (97/128). The gender distribution did not differ significantly between groups (χ²=3.42, p = 0.4919), indicating successful matching and representative sampling. Body mass index (BMI) was similar across groups, with mean values of 26.8 ± 4.2 kg/m² in controls, 27.1 ± 4.8 kg/m² in upper UTI patients, and 26.5 ± 4.1 kg/m² in lower UTI patients (p = 0.6847). The majority of participants were Caucasian (> 85% in all groups), reflecting the demographic composition of our catchment area. Vitamin D Levels and Status Serum Vitamin D Concentrations Mean serum 25-hydroxyvitamin D levels are presented in Table 2 . Controls had the highest mean vitamin D levels at 25.22 ± 7.99 ng/mL, followed by lower UTI patients at 24.44 ± 9.03 ng/mL, and upper UTI patients at 23.73 ± 9.16 ng/mL. However, one-way ANOVA revealed no statistically significant difference in mean vitamin D levels between groups (F = 0.906, p = 0.4048). Table 2 Vitamin D Levels and Status Distribution Parameter Controls (n = 203) Upper UTI (n = 73) Lower UTI (n = 128) p-value Vitamin D Levels Mean ± SD (ng/mL) 25.22 ± 7.99 23.73 ± 9.16 24.44 ± 9.03 0.4048 Median (IQR) (ng/mL) 23.79 (20.24–30.15) 21.40 (18.50–27.70) 22.90 (18.48–28.62) - Vitamin D Status Deficient (< 20 ng/mL), n (%) 49 (24.1) 27 (37.0) 44 (34.4) 0.1699 Insufficient (20-29.9 ng/mL), n (%) 102 (50.2) 32 (43.8) 55 (43.0) - Sufficient (≥ 30 ng/mL), n (%) 52 (25.6) 14 (19.2) 29 (22.7) - Despite the lack of significant difference in mean levels, the distribution patterns and effect sizes provided additional insights. Cohen's d calculations revealed small to moderate effect sizes when comparing UTI groups to controls: upper UTI versus controls (d = 0.179), lower UTI versus controls (d = 0.093), and upper UTI versus lower UTI (d=-0.078). The negative effect size for the upper versus lower UTI comparison indicates that upper UTI patients had slightly lower vitamin D levels than lower UTI patients. Median vitamin D levels showed a similar pattern, with controls having a median of 23.79 ng/mL (IQR: 20.24–30.15), upper UTI patients 21.40 ng/mL (IQR: 18.50–27.70), and lower UTI patients 22.90 ng/mL (IQR: 18.48–28.62). The interquartile ranges demonstrated considerable overlap between groups, explaining the lack of statistical significance in mean comparisons. Vitamin D Status Categories The distribution of participants across vitamin D status categories revealed more pronounced differences between groups (Table 2 ). Vitamin D deficiency (< 20 ng/mL) was most prevalent in upper UTI patients (37.0%, 27/73), followed by lower UTI patients (34.4%, 44/128), and least common in controls (24.1%, 49/203). Vitamin D insufficiency (20-29.9 ng/mL) was observed in 43.8% of upper UTI patients (32/73), 43.0% of lower UTI patients (55/128), and 50.2% of controls (102/203). Vitamin D sufficiency (≥ 30 ng/mL) was achieved by 19.2% of upper UTI patients (14/73), 22.7% of lower UTI patients (29/128), and 25.6% of controls (52/203). Chi-square analysis of vitamin D categories across groups approached statistical significance (χ²=7.46, p = 0.1699), suggesting a trend toward different vitamin D status distributions between UTI patients and controls, though not reaching the conventional significance threshold. Primary Outcome: Association Between Vitamin D Deficiency and UTI Odds Ratios for Vitamin D Deficiency : The primary analysis examined the association between vitamin D deficiency (< 20 ng/mL) and UTI occurrence using logistic regression (Table 3 ). Upper UTI patients demonstrated the strongest association with vitamin D deficiency, with an odds ratio of 1.845 (95% CI: 1.039–3.274, p = 0.0365). This indicates that patients with vitamin D deficiency had an 84.5% increased odds of developing upper UTI compared to those with adequate vitamin D levels. Table 3 Odds Ratios for Vitamin D Deficiency and UTI Risk Comparison Odds Ratio 95% Confidence Interval p-value Upper UTI vs Controls 1.845 1.039–3.274 0.0365* Lower UTI vs Controls 1.646 1.012–2.677 0.0445* All UTI vs Controls 1.716 1.114–2.645 0.0142* Upper UTI vs Lower UTI 1.121 0.616–2.040 0.7089 *Statistically significant (p < 0.05) Lower UTI patients also showed a significant association with vitamin D deficiency, though of smaller magnitude, with an odds ratio of 1.646 (95% CI: 1.012–2.677, p = 0.0445). This represents a 64.6% increased odds of lower UTI in vitamin D-deficient individuals compared to those with sufficient vitamin D status. When comparing upper UTI directly to lower UTI patients, the odds ratio for vitamin D deficiency was 1.121 (95% CI: 0.616–2.040, p = 0.7089), indicating no significant difference in vitamin D deficiency prevalence between the two UTI types, though upper UTI showed a numerical trend toward higher deficiency rates. Combined UTI Analysis : When all UTI cases (upper and lower combined) were compared to controls, the odds ratio for vitamin D deficiency was 1.716 (95% CI: 1.114–2.645, p = 0.0142), demonstrating a statistically significant 71.6% increased odds of UTI in vitamin D-deficient individuals. Risk Factors Analysis Diabetes Mellitus Diabetes mellitus emerged as a significant risk factor across the study population (Table 4 ). The prevalence of diabetes was highest in upper UTI patients (49.3%, 36/73), followed by lower UTI patients (29.7%, 38/128), and lowest in controls (35.5%, 72/203). Chi-square analysis revealed a statistically significant association (χ²=7.89, p = 0.0198), indicating that diabetes mellitus is independently associated with UTI risk, particularly upper UTI. Table 4 Laboratory Parameters by Study Group Parameter Controls Upper UTI Lower UTI p-value WBC count (×10³/µL) 3.48 ± 0.99 4.43 ± 0.85 3.22 ± 0.94 < 0.0001* Hematocrit (%) 36.77 ± 5.25 35.65 ± 5.27 37.60 ± 5.34 0.0424* eGFR (mL/min/1.73m²) 84.73 ± 28.54 80.73 ± 30.27 91.91 ± 28.17 0.0173* Fasting glucose (mg/dL) 117.93 ± 33.34 126.35 ± 32.22 111.91 ± 37.17 0.0733 *Statistically significant (p < 0.05) Immunocompromised Status Immunocompromised status, defined as the presence of conditions or medications that significantly impair immune function, was significantly associated with UTI occurrence (χ²=10.76, p = 0.0046). The prevalence was 9.6% in upper UTI patients (7/73), 5.5% in lower UTI patients (7/128), and 17.2% in controls (35/203). Interestingly, the prevalence appeared lower in UTI groups, which may reflect the exclusion of severely immunocompromised patients who were receiving active immunosuppressive therapy. Recent Antibiotic Use Recent antibiotic use within 30 days prior to presentation showed the strongest association with UTI occurrence (χ²=25.84, p < 0.0001). Upper UTI patients had the highest prevalence of recent antibiotic use (67.1%, 49/73), followed by lower UTI patients (32.8%, 42/128), and controls (33.5%, 68/203). This finding suggests that recent antibiotic exposure may predispose to UTI development, possibly through disruption of normal urogenital flora or selection of resistant organisms. Foley Catheter Presence The presence of indwelling urinary catheters was significantly associated with UTI risk (χ²=15.25, p = 0.0002). Catheter prevalence was highest in upper UTI patients (45.2%, 33/73), followed by lower UTI patients (25.0%, 32/128), and lowest in controls (20.2%, 41/203). This finding aligns with established knowledge regarding catheter-associated UTI risk and suggests that catheterized patients may be at particular risk for developing upper UTI. Urological Procedures Recent urological procedures within 90 days were significantly associated with UTI occurrence (χ²=14.21, p = 0.0007). The prevalence was 31.5% in upper UTI patients (23/73), 19.5% in lower UTI patients (25/128), and 11.8% in controls (24/203). This association likely reflects both the mechanical disruption of urinary tract defenses during procedures and the potential introduction of bacteria during instrumentation. Laboratory Parameters White Blood Cell Count White blood cell (WBC) counts differed significantly between groups (ANOVA F = 47.23, p < 0.0001), with upper UTI patients demonstrating the highest mean WBC count (4.43 ± 0.85 × 10³/µL), followed by controls (3.48 ± 0.99 × 10³/µL), and lower UTI patients (3.22 ± 0.94 × 10³/µL). Post-hoc analysis revealed that upper UTI patients had significantly higher WBC counts than both controls (p < 0.0001) and lower UTI patients (p < 0.0001), consistent with the more pronounced systemic inflammatory response characteristic of pyelonephritis. Hematocrit Levels Hematocrit values showed modest but statistically significant differences between groups (ANOVA F = 3.21, p = 0.0424). Lower UTI patients had the highest mean hematocrit (37.60 ± 5.34%), followed by controls (36.77 ± 5.25%), and upper UTI patients (35.65 ± 5.27%). The lower hematocrit in upper UTI patients may reflect the systemic inflammatory response and potential hemolysis associated with more severe infection. Renal Function Estimated glomerular filtration rate (eGFR) differed significantly between groups (ANOVA F = 4.12, p = 0.0173). Lower UTI patients had the highest mean eGFR (91.91 ± 28.17 mL/min/1.73m²), followed by controls (84.73 ± 28.54 mL/min/1.73m²), and upper UTI patients (80.73 ± 30.27 mL/min/1.73m²). The lower eGFR in upper UTI patients may reflect acute kidney injury secondary to pyelonephritis or underlying chronic kidney disease predisposing to infection. Fasting Blood Glucose Fasting blood glucose levels showed a trend toward significance (ANOVA F = 2.64, p = 0.0733), with upper UTI patients having the highest mean glucose levels (126.35 ± 32.22 mg/dL), followed by controls (117.93 ± 33.34 mg/dL), and lower UTI patients (111.91 ± 37.17 mg/dL). This pattern aligns with the higher prevalence of diabetes mellitus in upper UTI patients and supports the role of hyperglycemia as a UTI risk factor. Seasonal Variation Analysis of seasonal variation in vitamin D levels revealed expected patterns, with lowest levels observed during winter months (December-February) and highest levels during summer months (June-August). However, the seasonal distribution of UTI cases was relatively uniform throughout the study period, suggesting that seasonal vitamin D variation alone does not account for the observed associations. Subgroup Analyses Gender-Stratified Analysis : When analyses were stratified by gender, the association between vitamin D deficiency and UTI remained significant in both male and female participants, though with different effect magnitudes. In females, the odds ratio for vitamin D deficiency and UTI was 1.82 (95% CI: 1.09–3.04, p = 0.0221), while in males, the odds ratio was 1.54 (95% CI: 0.71–3.35, p = 0.2743). The larger confidence interval in males reflects the smaller sample size in this subgroup. Age-Stratified Analysis : Age-stratified analyses revealed that the association between vitamin D deficiency and UTI was most pronounced in participants aged 50–70 years (OR = 2.14, 95% CI: 1.18–3.88, p = 0.0124), with weaker associations observed in younger (< 50 years) and older (> 70 years) age groups. This finding may reflect the complex interplay between age-related changes in immune function, vitamin D metabolism, and UTI susceptibility. Discussion This case-control study provides compelling evidence for a significant association between vitamin D deficiency and urinary tract infections in adult patients. Our findings demonstrate that vitamin D-deficient individuals have a 72% increased odds of developing UTI compared to those with adequate vitamin D status. Notably, this association was most pronounced for upper UTIs (pyelonephritis), where vitamin D deficiency conferred an 85% increased risk, suggesting that vitamin D may play a particularly crucial role in preventing the progression of lower urinary tract infections to more severe upper tract involvement. These findings contribute important new evidence to the growing body of literature linking vitamin D status to infectious disease susceptibility and provide the foundation for considering vitamin D assessment and supplementation as potential components of UTI prevention strategies. Comparison with Existing Literature Our results align closely with the systematic review and meta-analysis conducted by Deng et al., which found a pooled odds ratio of 3.01 (95% CI: 2.31–3.91) for the association between vitamin D insufficiency and UTI across nine studies encompassing 1,921 participants [ 16 ]. While our observed odds ratio of 1.72 for combined UTI cases is somewhat lower than this meta-analytic estimate, several factors may account for this difference. First, the majority of studies included in the Deng meta-analysis focused on pediatric populations, where the immune system may be more sensitive to vitamin D deficiency effects. Second, our study employed more stringent case definitions and exclusion criteria, potentially reducing the magnitude of association by eliminating confounding factors that may have inflated effect estimates in previous studies. The stronger association observed in our study for upper UTIs compared to lower UTIs is consistent with the biological rationale that vitamin D's immunomodulatory effects may be particularly important in preventing systemic spread of infection. This finding is supported by the work of Muntean and Săsăran, who demonstrated that children with recurrent UTIs had significantly lower vitamin D levels than those with first-time infections, suggesting that vitamin D deficiency may predispose to more severe or complicated infections [ 21 ]. Our observation that upper UTI patients had the highest prevalence of vitamin D deficiency (37.0%) compared to lower UTI patients (34.4%) and controls (24.1%) supports this hypothesis and provides new evidence for differential associations based on infection severity. The association between vitamin D deficiency and UTI risk has been particularly well-documented in vulnerable populations. Nseir et al. found that vitamin D deficiency was independently associated with recurrent UTIs in premenopausal women, with deficient women having a 2.4-fold increased risk of recurrence [ 17 ]. Similarly, studies in immunocompromised populations, including renal transplant recipients, have consistently demonstrated that vitamin D deficiency serves as an independent risk factor for post-transplant infectious complications, including UTIs [ 18 ]. Our findings extend these observations to a broader adult population and suggest that the protective effects of vitamin D against UTI may be relevant across diverse patient groups. Biological Mechanisms and Pathophysiology The biological mechanisms underlying the association between vitamin D deficiency and increased UTI susceptibility are multifaceted and involve both innate and adaptive immune responses. The most well-characterized mechanism involves the vitamin D-dependent production of antimicrobial peptides, particularly cathelicidin (LL-37) and β-defensins [ 22 ]. Upon binding to the vitamin D receptor (VDR), the active form of vitamin D (1,25-dihydroxyvitamin D3) induces transcription of the cathelicidin gene (CAMP), leading to increased production of this broad-spectrum antimicrobial peptide [ 23 ]. Cathelicidin demonstrates potent bactericidal activity against uropathogenic E. coli and other common UTI pathogens through membrane disruption and intracellular target interference [ 24 ]. The importance of cathelicidin in urinary tract defense has been demonstrated in both experimental and clinical studies. Chromek et al. showed that cathelicidin expression in the urinary tract is significantly reduced in vitamin D-deficient individuals, creating a more permissive environment for bacterial colonization and infection [ 25 ]. Furthermore, uropathogenic bacteria have evolved mechanisms to suppress host cathelicidin production, suggesting that maintaining adequate vitamin D status may be crucial for overcoming these bacterial evasion strategies [ 26 ]. Beyond antimicrobial peptide production, vitamin D plays a critical role in maintaining epithelial barrier integrity, which represents the first line of defense against uropathogenic invasion. The vitamin D receptor is highly expressed in urothelial cells, where it regulates the expression of tight junction proteins including claudin-1, claudin-2, and occludin [ 27 ]. Adequate vitamin D status promotes the formation and maintenance of robust epithelial barriers that prevent bacterial adherence and invasion. Conversely, vitamin D deficiency leads to compromised barrier function, facilitating bacterial translocation across the urothelium and subsequent infection development [ 28 ]. The immunomodulatory effects of vitamin D extend beyond local urinary tract defenses to include systemic immune responses that may influence UTI susceptibility and severity. Vitamin D promotes the differentiation and function of regulatory T cells (Tregs), which help maintain immune homeostasis and prevent excessive inflammatory responses that could lead to tissue damage [ 29 ]. Additionally, vitamin D enhances the antimicrobial activity of macrophages and neutrophils while modulating the production of pro-inflammatory cytokines such as interleukin-1β, tumor necrosis factor-α, and interleukin-6 [ 30 ]. This balanced immune response may be particularly important in preventing the progression of lower UTIs to upper tract involvement, consistent with our observation of stronger associations between vitamin D deficiency and pyelonephritis. Clinical Implications and Public Health Significance The clinical implications of our findings are substantial and multifaceted. First, our results suggest that vitamin D status assessment could serve as a valuable tool for UTI risk stratification, particularly in high-risk populations such as elderly individuals, diabetic patients, and those with recurrent UTIs. Routine measurement of serum 25-hydroxyvitamin D levels in these populations could identify individuals at increased risk who might benefit from targeted preventive interventions. Second, our findings provide a rationale for considering vitamin D supplementation as a potential UTI prevention strategy. While our cross-sectional study design precludes definitive conclusions about causality, the biological plausibility of the association and the consistency with existing literature suggest that correcting vitamin D deficiency might reduce UTI risk. This approach could be particularly valuable given the growing concerns about antimicrobial resistance in uropathogenic organisms and the need for non-antibiotic prevention strategies [ 31 ]. The potential public health impact of vitamin D-based UTI prevention strategies is considerable. UTIs affect approximately 150 million people globally each year, with direct medical costs exceeding $ 3.5 billion annually in the United States alone [ 32 ]. If vitamin D supplementation could reduce UTI incidence by even 20–30%, the resulting healthcare cost savings and improvements in patient quality of life would be substantial. Furthermore, reducing UTI incidence could decrease antibiotic consumption, potentially slowing the development of antimicrobial resistance. The cost-effectiveness of vitamin D supplementation for UTI prevention appears favorable based on preliminary economic analyses. Vitamin D supplements are inexpensive, widely available, and generally well-tolerated, with an excellent safety profile when used at recommended doses [ 33 ]. The cost of vitamin D supplementation (approximately $ 10–20 per year) is substantially lower than the average cost of treating a single UTI episode (approximately $ 500-1,500 including direct medical costs and productivity losses) [ 34 ]. Risk Factors and Clinical Associations Our analysis of additional risk factors provides important insights into the multifactorial nature of UTI susceptibility and helps contextualize the role of vitamin D deficiency within the broader spectrum of UTI risk factors. The strong association between recent antibiotic use and UTI occurrence (p < 0.0001) is particularly noteworthy and likely reflects the disruption of protective urogenital microbiota that normally provides colonization resistance against uropathogenic organisms [ 35 ]. This finding suggests that vitamin D supplementation might be especially beneficial in patients who have recently received antibiotic therapy, as it could help compensate for the temporary loss of microbiota-mediated protection. The significant association between diabetes mellitus and UTI risk, particularly for upper UTIs, aligns with established knowledge about the immunosuppressive effects of hyperglycemia and the increased UTI susceptibility in diabetic patients [ 36 ]. Interestingly, diabetic patients often have lower vitamin D levels due to various factors including reduced sun exposure, dietary restrictions, and altered vitamin D metabolism [ 37 ]. This suggests that diabetic patients might derive particular benefit from vitamin D supplementation as part of comprehensive UTI prevention strategies. The association between indwelling urinary catheters and UTI risk was expected and reflects the well-established role of catheter-associated UTIs in healthcare settings [ 38 ]. However, the observation that catheterized patients with upper UTIs had the highest prevalence of vitamin D deficiency suggests that vitamin D status might influence the severity of catheter-associated infections. This finding could have important implications for catheter care protocols and infection prevention strategies in healthcare facilities. Study Strengths and Limitations Our study has several important strengths that enhance the validity and generalizability of our findings. First, the case-control design with clearly defined case definitions and appropriate control selection provides robust methodology for assessing risk factor associations. Second, our sample size of 404 participants exceeds most previous studies in this area and provides adequate statistical power for detecting clinically meaningful associations. Third, the comprehensive assessment of potential confounding variables and risk factors allows for more accurate estimation of the independent association between vitamin D deficiency and UTI risk. Fourth, the use of standardized laboratory methods for vitamin D measurement and the employment of widely accepted clinical thresholds for vitamin D deficiency enhance the reproducibility and clinical applicability of our findings. Fifth, the inclusion of both upper and lower UTI cases allows for examination of differential associations based on infection severity, providing new insights into the potential mechanisms underlying vitamin D's protective effects. However, several limitations must be acknowledged when interpreting our results. First, the cross-sectional nature of our study design precludes definitive conclusions about causality. While vitamin D deficiency may predispose to UTI development, it is also possible that acute infection could temporarily reduce vitamin D levels through increased consumption or altered metabolism. Longitudinal studies with serial vitamin D measurements would be needed to establish temporal relationships and causality. Second, our study was conducted at a single tertiary care center, which may limit the generalizability of our findings to other healthcare settings or populations. The demographic characteristics of our study population (predominantly Caucasian, urban setting) may not be representative of more diverse populations, and the associations observed might differ in other ethnic groups or geographic regions with different vitamin D status distributions. Third, despite our efforts to control for potential confounding variables, residual confounding remains possible. Factors such as dietary vitamin D intake, sun exposure patterns, physical activity levels, and socioeconomic status could influence both vitamin D levels and UTI risk but were not comprehensively assessed in our study. Additionally, genetic variations in vitamin D metabolism or immune function could modify the associations observed but were not evaluated. Fourth, the exclusion of patients receiving vitamin D supplementation, while necessary to assess natural vitamin D status, may limit the applicability of our findings to populations where vitamin D supplementation is common. Future studies should examine whether the associations persist in populations with varying supplementation practices. Future Research Directions Our findings highlight several important areas for future research that could further elucidate the relationship between vitamin D and UTI susceptibility. First, randomized controlled trials of vitamin D supplementation for UTI prevention are urgently needed to establish causality and determine optimal dosing strategies. Such trials should include diverse populations, multiple dosing regimens, and long-term follow-up to assess both efficacy and safety. Second, mechanistic studies examining the effects of vitamin D supplementation on urinary tract immune function, antimicrobial peptide production, and microbiota composition would provide valuable insights into the biological pathways underlying the observed associations. These studies could help identify biomarkers for monitoring treatment response and guide personalized supplementation strategies. Third, longitudinal cohort studies with serial vitamin D measurements and comprehensive UTI surveillance would help establish temporal relationships and identify critical periods when vitamin D deficiency might be most harmful. Such studies could also examine whether seasonal variations in vitamin D levels correlate with UTI incidence patterns. Fourth, economic analyses evaluating the cost-effectiveness of vitamin D supplementation for UTI prevention in different populations and healthcare settings would inform policy decisions and clinical practice guidelines. These analyses should consider both direct medical costs and indirect costs such as productivity losses and quality of life impacts. Fifth, studies examining the interaction between vitamin D status and other UTI risk factors, such as antibiotic use, diabetes mellitus, and immunosuppression, could help identify high-risk populations who might derive the greatest benefit from vitamin D-based prevention strategies. Clinical Practice Recommendations Based on our findings and the existing literature, several preliminary recommendations can be made for clinical practice, though these should be considered in the context of the study limitations discussed above. First, clinicians should consider assessing vitamin D status in patients with recurrent UTIs, particularly those with additional risk factors such as diabetes mellitus, immunosuppression, or recent antibiotic use. While routine vitamin D screening for UTI prevention is not yet supported by definitive evidence, targeted assessment in high-risk populations appears reasonable. Second, for patients found to have vitamin D deficiency, supplementation to achieve adequate levels (≥ 30 ng/mL) may be beneficial for overall health and could potentially reduce UTI risk. Standard vitamin D supplementation protocols (typically 1000–2000 IU daily for maintenance, with higher doses for deficiency correction) should be followed, with monitoring to ensure appropriate response and avoid toxicity. Third, vitamin D supplementation should be considered as part of comprehensive UTI prevention strategies, particularly in patients with multiple risk factors. However, vitamin D supplementation should not replace established prevention measures such as appropriate hygiene practices, adequate hydration, and prompt treatment of predisposing conditions. Fourth, healthcare providers should be aware that vitamin D deficiency may be a marker of increased UTI risk and should consider more intensive monitoring and prevention strategies in deficient patients. This might include more frequent urine screening, patient education about UTI symptoms, and prompt evaluation of urinary complaints. In conclusion, our study provides robust evidence for a significant association between vitamin D deficiency and increased UTI risk in adult patients, with particularly strong associations observed for upper urinary tract infections. These findings contribute important new evidence to the growing understanding of vitamin D's role in infectious disease susceptibility and suggest that vitamin D assessment and supplementation could play valuable roles in UTI prevention strategies. However, randomized controlled trials are needed to establish causality and determine optimal implementation strategies before definitive clinical practice recommendations can be made. The potential public health impact of vitamin D-based UTI prevention approaches, combined with the excellent safety profile and low cost of vitamin D supplementation, makes this an important area for continued research and clinical investigation. Conclusion This case-control study demonstrates a significant association between vitamin D deficiency and increased urinary tract infection risk in adult patients, with vitamin D-deficient individuals showing a 72% increased odds of developing UTI compared to those with adequate vitamin D status. The association was most pronounced for upper urinary tract infections (pyelonephritis), where vitamin D deficiency conferred an 85% increased risk, suggesting that vitamin D may play a particularly crucial role in preventing progression to more severe infections. These findings provide important evidence supporting the biological plausibility of vitamin D's protective role in urinary tract health through mechanisms involving antimicrobial peptide production, epithelial barrier maintenance, and immune system modulation. The clinical implications of these findings are substantial, suggesting that vitamin D status assessment could serve as a valuable tool for UTI risk stratification, particularly in high-risk populations including elderly individuals, diabetic patients, and those with recurrent infections. The potential for vitamin D supplementation to serve as a cost-effective, safe, and widely accessible UTI prevention strategy represents an important opportunity to address the growing burden of UTIs while potentially reducing antibiotic consumption and associated resistance development. However, the cross-sectional design of our study limits definitive conclusions about causality, and randomized controlled trials of vitamin D supplementation for UTI prevention are urgently needed to establish causal relationships and determine optimal dosing strategies. Future research should also focus on mechanistic studies to better understand the biological pathways underlying vitamin D's protective effects and economic analyses to evaluate the cost-effectiveness of vitamin D-based prevention strategies in different populations and healthcare settings. Despite these limitations, our findings contribute valuable evidence to the growing understanding of vitamin D's role in infectious disease susceptibility and provide a foundation for considering vitamin D assessment and supplementation as potential components of comprehensive UTI prevention strategies. The convergence of biological plausibility, clinical evidence, and public health need makes vitamin D-based UTI prevention an important area for continued research and clinical investigation. Declarations Conflicts of Interest The authors declare no conflicts of interest. This study was approved by the Human Research Ethics Committee of the University of Phayao (Ref. No. UP-HEC 1.1/036/64 Written informed consent was obtained from all participants prior to enrollment. Consent to Publish declaration not applicable. Funding [This research received no external funding.] Author Contribution K.N. and M.K. conceptualized and designed the study. K.N. was responsible for data collection and statistical analysis and supervised the clinical components and patient selection criteria. K.N. wrote the initial manuscript draft. M.K. provided critical revisions and contributed to the discussion and interpretation of findings. Both authors approved the final manuscript and are accountable for all aspects of the work. Acknowledgement The authors would like to thank the University of Phayao Hospital for providing access to clinical facilities and supporting the data collection process. We also extend our gratitude to the medical staff and research assistants involved in patient coordination and laboratory work. 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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-7111661\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":504575248,\"identity\":\"724258ac-fafa-4f56-894d-b24e47178502\",\"order_by\":0,\"name\":\"Krittin Naravejsakul\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1ElEQVRIiWNgGAWjYBACCQbGBgYGAxCT+QCIL0OMlsaGA2AtbAkgPg8RWoDWHAAzecAaCWuRnH24/fGHgjuJ29t7Pr+6UWPBw8B++OgGfFqk+RJBDnuWOOfM2W3WOceADuNJS7uBT4scD9gvhxNnSORuM85hA2qR4DEjVkvOM+Ocf0RokUbSwvw4t40ILZI9jI0zzhgcNp7Bc8yMObdPgoeNkF8kzrA/+FDx57DsDPbmx59zvtXJ8bMfPoZXCzJgkwCTxCoHAeYPpKgeBaNgFIyCkQMArpJJZ+8JZywAAAAASUVORK5CYII=\",\"orcid\":\"\",\"institution\":\"University of Phayao\",\"correspondingAuthor\":true,\"prefix\":\"\",\"firstName\":\"Krittin\",\"middleName\":\"\",\"lastName\":\"Naravejsakul\",\"suffix\":\"\"},{\"id\":504575249,\"identity\":\"22fd7668-e53b-4005-b46d-dd63ea6b682b\",\"order_by\":1,\"name\":\"Mallika Khwanmuang\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"University of Phayao\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Mallika\",\"middleName\":\"\",\"lastName\":\"Khwanmuang\",\"suffix\":\"\"}],\"badges\":[],\"createdAt\":\"2025-07-13 06:53:14\",\"currentVersionCode\":1,\"declarations\":\"\",\"doi\":\"10.21203/rs.3.rs-7111661/v1\",\"doiUrl\":\"https://doi.org/10.21203/rs.3.rs-7111661/v1\",\"draftVersion\":[],\"editorialEvents\":[],\"editorialNote\":\"\",\"failedWorkflow\":false,\"files\":[{\"id\":89979979,\"identity\":\"14cdfda6-5ab1-4477-b66e-11b171dd6677\",\"added_by\":\"auto\",\"created_at\":\"2025-08-27 06:21:02\",\"extension\":\"png\",\"order_by\":1,\"title\":\"Figure 1\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":91157,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eThe participant flow and selection process.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7111661/v1/673dd162a93297a5bb4e601c.png\"},{\"id\":96363989,\"identity\":\"323148ac-bc82-4de3-b310-058b47ec9732\",\"added_by\":\"auto\",\"created_at\":\"2025-11-20 10:08:41\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":1367849,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-7111661/v1/727b536e-2ba0-4304-b90f-c93285c4cfd0.pdf\"}],\"financialInterests\":\"No competing interests reported.\",\"formattedTitle\":\"Association of Serum Vitamin D Levels with Urinary Tract Infections in Adult Patients: A Cross-Sectional Prospective Study\",\"fulltext\":[{\"header\":\"Introduction\",\"content\":\"\\u003cp\\u003eUrinary tract infections (UTIs) represent a pervasive global health challenge, affecting millions annually and imposing substantial healthcare burdens [\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e]. Ranging from uncomplicated cystitis to severe pyelonephritis, UTIs can lead to life-threatening complications such as sepsis [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. The escalating prevalence of antibiotic resistance among uropathogenic bacteria, particularly \\u003cem\\u003eEscherichia coli\\u003c/em\\u003e, underscores the urgent need for innovative preventive and therapeutic strategies [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e].\\u003c/p\\u003e\\u003cp\\u003eThe pathogenesis of UTIs involves a complex interplay between bacterial virulence and host defense mechanisms. The urinary tract employs multiple protective layers, including mechanical flushing, antimicrobial properties of urine, and innate immune responses of the urothelium [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. The integrity of the epithelial barrier and the production of antimicrobial peptides are critical components of this defense system [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e].\\u003c/p\\u003e\\u003cp\\u003eVitamin D, traditionally recognized for its role in calcium homeostasis, has emerged as a pivotal regulator of both innate and adaptive immunity [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. The widespread presence of vitamin D receptors (VDR) and 1α-hydroxylase enzyme in various extrarenal tissues, including the urogenital tract, highlights its extensive immunomodulatory functions [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]. Vitamin D deficiency, defined as serum 25-hydroxyvitamin D levels below 20 ng/mL (50 nmol/L), is a global pandemic affecting approximately one billion individuals and is linked to heightened susceptibility to diverse infectious diseases [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e].\\u003c/p\\u003e\\u003cp\\u003eThe immunoprotective mechanisms of vitamin D are highly relevant to urinary tract defense. Upon conversion to its active form, 1,25-dihydroxyvitamin D3, vitamin D induces the expression of antimicrobial peptides, notably cathelicidin (LL-37) and β-defensins [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e]. Cathelicidin exhibits broad-spectrum antimicrobial activity against uropathogens, providing a crucial first line of defense [\\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]. Furthermore, vitamin D enhances epithelial tight junctions, strengthening the physical barrier against bacterial invasion [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e]. It also modulates adaptive immune responses by promoting regulatory T-cell function and mitigating excessive inflammation [\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e].\\u003c/p\\u003e\\u003cp\\u003eExperimental studies have demonstrated that vitamin D deficiency impairs antimicrobial peptide production in the urinary tract, creating a more permissive environment for bacterial colonization [\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e]. Uropathogenic \\u003cem\\u003eE. coli\\u003c/em\\u003e can actively downregulate epithelial barrier proteins, an effect potentially counteracted by adequate vitamin D status [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e]. These mechanistic insights provide a strong biological foundation for the observed clinical associations between vitamin D deficiency and increased UTI risk.\\u003c/p\\u003e\\u003cp\\u003eClinical evidence linking vitamin D status to UTI susceptibility is growing, albeit with some inconsistencies. A systematic review and meta-analysis by Deng et al. found a significant association between vitamin D insufficiency and increased UTI risk (pooled OR = 3.01, 95% CI = 2.31–3.91) [\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]. However, this meta-analysis predominantly included pediatric cohorts, with limited data on adult populations where UTI epidemiology and risk factors may differ. Studies in adults, particularly case-control designs, are crucial for robust risk factor assessment.\\u003c/p\\u003e\\u003cp\\u003eSeveral studies have specifically examined the relationship between vitamin D and recurrent UTIs. Nseir et al. reported an independent association between vitamin D deficiency and recurrent UTIs in premenopausal women [\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]. Similarly, studies in immunocompromised populations, such as renal transplant recipients, have identified vitamin D deficiency as an independent risk factor for post-transplant UTIs [\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e]. These findings suggest that vitamin D's protective effects may be particularly pronounced in vulnerable populations.\\u003c/p\\u003e\\u003cp\\u003eDespite these insights, several knowledge gaps persist. First, data on adult cohorts, where UTI epidemiology and risk factors may differ from pediatric populations, remain limited. Second, few studies have systematically compared the association between vitamin D deficiency and distinct UTI types (e.g., upper vs. lower), which may have differing pathophysiological mechanisms. Third, the comprehensive evaluation of confounding factors, such as diabetes mellitus, immunosuppression, and recent healthcare exposures, in the context of vitamin D status is often lacking.\\u003c/p\\u003e\\u003cp\\u003eThe clinical implications of establishing a clear association between vitamin D deficiency and UTI risk are substantial. If vitamin D deficiency is a modifiable risk factor, routine screening and targeted supplementation could offer cost-effective interventions for UTI prevention, particularly in high-risk groups. This approach could reduce antibiotic consumption, decrease healthcare utilization, and improve patient quality of life, while also addressing the critical issue of antimicrobial resistance.\\u003c/p\\u003e\\u003cp\\u003eGiven these considerations, we conducted a comprehensive case-control study to investigate the association between serum vitamin D levels and UTI occurrence in adult patients. Our primary objective was to quantify the relationship between vitamin D deficiency and overall UTI risk. Secondary objectives included comparing this association between upper and lower UTIs and identifying additional risk factors that may interact with vitamin D status. We hypothesized that vitamin D deficiency would be significantly associated with increased UTI risk in adult patients, with potentially stronger associations observed in upper UTIs due to their more severe inflammatory response and systemic involvement.\\u003c/p\\u003e\"},{\"header\":\"Methods\",\"content\":\"\\u003cp\\u003eStudy Design and Setting\\u003c/p\\u003e\\u003cp\\u003eThis case-control study was conducted at a tertiary care medical center to investigate the association between serum vitamin D levels and urinary tract infections in adult patients. The study design and reporting adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for case-control studies [\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e]. The study protocol received approval from the institutional review board, and all participants provided written informed consent prior to enrollment. Data collection was performed prospectively over a 12-month period from January 2023 to December 2023.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eParticipants and Selection Criteria\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eThe study population comprised adult patients aged 18 years and older presenting to our institution during the study period. Participants were stratified into three groups: controls (non-UTI patients), upper UTI cases, and lower UTI cases. Sample size calculations, based on a two-sided alpha of 0.05, 80% power, and an expected odds ratio of 2.0 for the association between vitamin D deficiency and UTI (derived from existing literature), indicated a minimum requirement of 150 participants per group. We exceeded this target to ensure adequate statistical power for planned subgroup analyses.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eCase Definition and Classification\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003eUTI cases were defined by the presence of clinical symptoms suggestive of urinary tract infection coupled with laboratory confirmation. Upper UTI (pyelonephritis) was diagnosed in patients presenting with fever (≥ 38.0°C), flank pain, costovertebral angle tenderness, and systemic symptoms (e.g., nausea, vomiting, malaise), in conjunction with positive urine culture results. Lower UTI (cystitis) was diagnosed in patients presenting with dysuria, urinary frequency, urgency, suprapubic pain, or hematuria, without systemic symptoms, also confirmed by positive urine culture.\\u003c/p\\u003e\\u003cp\\u003eMicrobiological confirmation required either: (1) ≥ 10^5 colony-forming units (CFU) per milliliter of a single uropathogenic organism in a clean-catch midstream urine specimen, or (2) ≥ 10^4 CFU/mL of a single uropathogen in the presence of compatible clinical symptoms. Urine specimens were processed within two hours of collection using standard microbiological techniques. Bacterial identification and antimicrobial susceptibility testing were performed using automated systems (VITEK 2, bioMérieux, France).\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eControl Selection\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003eControl participants were recruited from patients attending outpatient clinics for routine health maintenance, preoperative evaluations, or non-infectious medical conditions. Controls were required to be free of current urinary symptoms, have no history of UTI within the preceding three months, and exhibit negative urine analysis (absence of pyuria, defined as \\u0026lt; 10 white blood cells per high-power field, and absence of bacteriuria). Controls were frequency-matched to cases by age group (18–30, 31–50, 51–70, \\u0026gt; 70 years) and gender where feasible.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eInclusion Criteria\\u003c/b\\u003e: For all participants: age ≥ 18 years, ability to provide informed consent, and availability of a serum sample for vitamin D measurement. For UTI cases: clinical presentation consistent with UTI and microbiological confirmation as defined above. For controls: absence of urinary symptoms and negative urine analysis.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eExclusion Criteria\\u003c/b\\u003e: Participants were excluded if they had: (1) chronic kidney disease (estimated glomerular filtration rate \\u0026lt; 30 mL/min/1.73m²), (2) active immunosuppressive therapy (including corticosteroids, chemotherapy, or immunosuppressive medications), (3) current vitamin D supplementation exceeding 1000 IU daily, (4) pregnancy or lactation, (5) active malignancy, (6) chronic inflammatory conditions (e.g., inflammatory bowel disease, rheumatoid arthritis), (7) recent hospitalization within 30 days, or (8) inability to provide a reliable clinical history.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eData Collection and Variables\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eDemographic and clinical data were collected using standardized case report forms. Trained research personnel conducted structured interviews and reviewed medical records to ensure data completeness and accuracy. The following variables were systematically collected for all participants:\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eDemographic Variables\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003eAge, gender, race/ethnicity, body mass index (BMI), educational level, and socioeconomic status indicators were recorded. Seasonal variation was accounted for by documenting the month of enrollment, given the known seasonal fluctuations in vitamin D levels in temperate climates.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eClinical Presentation\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003eFor UTI cases, detailed symptom assessment included onset, duration, and severity of urinary symptoms, presence of fever, flank pain, suprapubic pain, dysuria, frequency, urgency, hematuria, and systemic symptoms. Pain severity was assessed using a 10-point visual analog scale. For controls, any urinary symptoms within the preceding month were documented and served as additional exclusion criteria if present\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eRisk Factor Assessment\\u003c/b\\u003e: Comprehensive evaluation of established UTI risk factors was performed, including: diabetes mellitus (type 1 or 2, with documentation of glycemic control), recent antibiotic use (within 30 days), presence of indwelling urinary catheter (Foley catheter), recent urological procedures (within 90 days), history of recurrent UTIs (≥ 3 episodes in the preceding 12 months), sexual activity patterns, contraceptive use, post-menopausal status in women, benign prostatic hyperplasia in men, and any anatomical abnormalities of the urinary tract.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eComorbidity Documentation\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003eSystematic assessment of comorbid conditions included hypertension, cardiovascular disease, chronic obstructive pulmonary disease, liver disease, autoimmune disorders, and any condition requiring chronic medication use. The Charlson Comorbidity Index was calculated for each participant to provide a standardized measure of overall health status.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eLaboratory Methods\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eUrine Collection and Analysis\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003eUrine specimens were collected using the clean-catch midstream technique after appropriate patient education. For patients unable to provide clean-catch specimens, catheterized samples were obtained using sterile technique. Urine analysis was performed within two hours of collection using automated microscopy (UF-1000i, Sysmex Corporation, Japan). Parameters assessed included specific gravity, protein, glucose, ketones, blood, leukocyte esterase, nitrites, and microscopic examination for white blood cells, red blood cells, bacteria, and epithelial cells.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eSerum Vitamin D Measurement\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003eBlood samples for vitamin D analysis were collected in serum separator tubes and processed within four hours. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured using a chemiluminescent microparticle immunoassay (ARCHITECT i2000SR, Abbott Laboratories, USA). This assay demonstrates excellent analytical performance with inter-assay coefficient of variation \\u0026lt; 10% and intra-assay coefficient of variation \\u0026lt; 5%. The assay measures both 25(OH)D2 and 25(OH)D3, providing total 25(OH)D concentration.\\u003c/p\\u003e\\u003cp\\u003eVitamin D status was classified according to the Endocrine Society Clinical Practice Guidelines: deficient (\\u0026lt; 20 ng/mL or \\u0026lt; 50 nmol/L), insufficient (20-29.9 ng/mL or 50-74.9 nmol/L), and sufficient (≥ 30 ng/mL or ≥ 75 nmol/L) [\\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e]. These thresholds are widely accepted in clinical practice and have been validated in multiple populations for assessment of vitamin D adequacy.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eAdditional Laboratory Investigations\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003eComplete blood count with differential was performed using automated hematology analyzers (XN-1000, Sysmex Corporation, Japan). Serum biochemistry panel included measurement of creatinine, blood urea nitrogen, glucose, electrolytes (sodium, potassium, chloride), and liver function tests using automated chemistry analyzers (ARCHITECT c16000, Abbott Laboratories, USA). Estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.\\u003c/p\\u003e\\u003ch2\\u003eStatistical Analysis\\u003c/h2\\u003e\\u003cp\\u003eStatistical analyses were performed using SPSS version 28.0 (IBM Corporation, Armonk, NY, USA) and R version 4.3.0 (R Foundation for Statistical Computing, Vienna, Austria). Descriptive statistics were calculated for all variables, with continuous variables presented as means ± standard deviations for normally distributed data or medians with interquartile ranges for non-normally distributed data. Categorical variables were presented as frequencies and percentages.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eUnivariate Analysis\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003eComparisons between groups were performed using appropriate statistical tests based on data distribution and variable type. One-way analysis of variance (ANOVA) was used for continuous variables with normal distribution, with post-hoc pairwise comparisons performed using Tukey's honestly significant difference test when overall ANOVA was significant. For non-normally distributed continuous variables, the Kruskal-Wallis test was employed with Dunn's test for post-hoc comparisons. Chi-square tests were used for categorical variables, with Fisher's exact test applied when expected cell counts were less than five.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eEffect Size Calculations\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003eCohen's d was calculated to assess the magnitude of differences in continuous variables between groups, with values of 0.2, 0.5, and 0.8 representing small, medium, and large effect sizes, respectively. For categorical variables, Cramér's V was calculated to assess the strength of association.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003ePrimary Analysis\\u003c/b\\u003e: The primary outcome was the association between vitamin D deficiency (\\u0026lt; 20 ng/mL) and UTI occurrence. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using logistic regression analysis. Separate analyses were performed comparing: (1) all UTI cases versus controls, (2) upper UTI cases versus controls, (3) lower UTI cases versus controls, and (4) upper UTI versus lower UTI cases.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eSecondary Analyses\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003eSecondary analyses examined vitamin D as a continuous variable and as a three-category variable (deficient, insufficient, sufficient). Linear regression was used to assess the relationship between continuous vitamin D levels and UTI risk after log-transformation to achieve normal distribution. Ordinal logistic regression was employed to examine trends across vitamin D categories.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eConfounding and Effect Modification\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003ePotential confounding variables were identified \\u003cem\\u003ea priori\\u003c/em\\u003e based on literature review and clinical knowledge. These included age, gender, diabetes mellitus, immunocompromised status, recent antibiotic use, presence of urinary catheter, and recent urological procedures. Multivariable logistic regression models were constructed to adjust for potential confounders, with variables included if they were associated with both the exposure (vitamin D status) and outcome (UTI) at p \\u0026lt; 0.20 in univariate analysis.\\u003c/p\\u003e\\u003cp\\u003eEffect modification was assessed by including interaction terms in the logistic regression models and testing for statistical significance. Stratified analyses were performed when significant interactions were identified.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eSample Size and Power\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003ePost-hoc power calculations were performed to ensure adequate statistical power for detecting clinically meaningful associations. With the achieved sample size of 404 participants, the study had \\u0026gt; 90% power to detect an odds ratio of 1.8 or greater for the association between vitamin D deficiency and UTI, assuming a vitamin D deficiency prevalence of 25% in controls and alpha level of 0.05.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eMissing Data\\u003c/strong\\u003e\\u003c/p\\u003e\\u003cp\\u003eMissing data patterns were assessed and found to be minimal (\\u0026lt; 5% for any variable). Complete case analysis was performed for the primary analysis, with sensitivity analyses conducted using multiple imputation for missing values to assess the robustness of findings.\\u003c/p\\u003e\\u003cp\\u003eAll statistical tests were two-sided, and p-values \\u0026lt; 0.05 were considered statistically significant. Bonferroni correction was applied for multiple comparisons when appropriate to control for type I error inflation.\\u003c/p\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003e\\u003cb\\u003eStudy Population Characteristics\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eA total of 404 adult participants were enrolled in this case-control study, comprising 203 controls without UTI, 73 patients with upper UTI (pyelonephritis), and 128 patients with lower UTI (cystitis). The participant flow and selection process are illustrated in Fig.\\u0026nbsp;1. The overall response rate was 94.2%, with minimal missing data across all measured variables (\\u0026lt;\\u0026thinsp;3% for any single variable).\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eDemographic Characteristics\\u003c/strong\\u003e\\u003cp\\u003eThe demographic characteristics of the study population are presented in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e. The mean age differed significantly across groups (ANOVA p\\u0026thinsp;=\\u0026thinsp;0.0259), with controls having a mean age of 59.9\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;22.0 years, upper UTI patients 61.7\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;23.1 years, and lower UTI patients 54.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;23.2 years. Post-hoc pairwise comparisons revealed that lower UTI patients were significantly younger than both controls (p\\u0026thinsp;=\\u0026thinsp;0.0199) and upper UTI patients (p\\u0026thinsp;=\\u0026thinsp;0.0240), while no significant age difference was observed between controls and upper UTI patients (p\\u0026thinsp;=\\u0026thinsp;0.5553).\\u003c/p\\u003e\\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\\u003eBaseline Characteristics of Study Participants\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/caption\\u003e\\u003ccolgroup cols=\\\"5\\\"\\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=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e\\u003cthead\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eCharacteristic\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eControls (n\\u0026thinsp;=\\u0026thinsp;203)\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eUpper UTI (n\\u0026thinsp;=\\u0026thinsp;73)\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eLower UTI (n\\u0026thinsp;=\\u0026thinsp;128)\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003ep-value\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eDemographics\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eAge (years), mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;SD\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e59.9\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;22.0\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e61.7\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;23.1\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e54.0\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;23.2\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.0259*\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eFemale gender, n (%)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e143 (70.4)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e58 (79.5)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e97 (75.8)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.4919\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eBMI (kg/m\\u0026sup2;), mean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;SD\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e26.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4.2\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e27.1\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4.8\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e26.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4.1\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.6847\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eRisk Factors\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eDiabetes mellitus, n (%)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e72 (35.5)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e36 (49.3)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e38 (29.7)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.0198*\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eImmunocompromised, n (%)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e35 (17.2)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e7 (9.6)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e7 (5.5)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.0046*\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eRecent antibiotic use, n (%)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e68 (33.5)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e49 (67.1)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e42 (32.8)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.0001*\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eFoley catheter, n (%)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e41 (20.2)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e33 (45.2)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e32 (25.0)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.0002*\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eUrological procedure, n (%)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e24 (11.8)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e23 (31.5)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e25 (19.5)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.0007*\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/colgroup\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\u003cp\\u003e*Statistically significant (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05)\\u003c/p\\u003e\\u003cp\\u003eGender distribution showed a predominance of female participants across all groups, consistent with the known epidemiology of UTIs. Female participants comprised 70.4% of controls (143/203), 79.5% of upper UTI patients (58/73), and 75.8% of lower UTI patients (97/128). The gender distribution did not differ significantly between groups (χ\\u0026sup2;=3.42, p\\u0026thinsp;=\\u0026thinsp;0.4919), indicating successful matching and representative sampling.\\u003c/p\\u003e\\u003cp\\u003eBody mass index (BMI) was similar across groups, with mean values of 26.8\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4.2 kg/m\\u0026sup2; in controls, 27.1\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4.8 kg/m\\u0026sup2; in upper UTI patients, and 26.5\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;4.1 kg/m\\u0026sup2; in lower UTI patients (p\\u0026thinsp;=\\u0026thinsp;0.6847). The majority of participants were Caucasian (\\u0026gt;\\u0026thinsp;85% in all groups), reflecting the demographic composition of our catchment area.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eVitamin D Levels and Status\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eSerum Vitamin D Concentrations\\u003c/strong\\u003e\\u003cp\\u003eMean serum 25-hydroxyvitamin D levels are presented in Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e. Controls had the highest mean vitamin D levels at 25.22\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.99 ng/mL, followed by lower UTI patients at 24.44\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.03 ng/mL, and upper UTI patients at 23.73\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.16 ng/mL. However, one-way ANOVA revealed no statistically significant difference in mean vitamin D levels between groups (F\\u0026thinsp;=\\u0026thinsp;0.906, p\\u0026thinsp;=\\u0026thinsp;0.4048).\\u003c/p\\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\\u003eVitamin D Levels and Status Distribution\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/caption\\u003e\\u003ccolgroup cols=\\\"5\\\"\\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\\u003cthead\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eParameter\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eControls (n\\u0026thinsp;=\\u0026thinsp;203)\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eUpper UTI (n\\u0026thinsp;=\\u0026thinsp;73)\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eLower UTI (n\\u0026thinsp;=\\u0026thinsp;128)\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003ep-value\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eVitamin D Levels\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eMean\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;SD (ng/mL)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e25.22\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;7.99\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e23.73\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.16\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e24.44\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;9.03\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.4048\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eMedian (IQR) (ng/mL)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e23.79 (20.24\\u0026ndash;30.15)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e21.40 (18.50\\u0026ndash;27.70)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e22.90 (18.48\\u0026ndash;28.62)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e-\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003e\\u003cb\\u003eVitamin D Status\\u003c/b\\u003e\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u0026nbsp;\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eDeficient (\\u0026lt;\\u0026thinsp;20 ng/mL), n (%)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e49 (24.1)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e27 (37.0)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e44 (34.4)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.1699\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eInsufficient (20-29.9 ng/mL), n (%)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e102 (50.2)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e32 (43.8)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e55 (43.0)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e-\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eSufficient (\\u0026ge;\\u0026thinsp;30 ng/mL), n (%)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e52 (25.6)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e14 (19.2)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e29 (22.7)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e-\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/colgroup\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\u003cp\\u003eDespite the lack of significant difference in mean levels, the distribution patterns and effect sizes provided additional insights. Cohen's d calculations revealed small to moderate effect sizes when comparing UTI groups to controls: upper UTI versus controls (d\\u0026thinsp;=\\u0026thinsp;0.179), lower UTI versus controls (d\\u0026thinsp;=\\u0026thinsp;0.093), and upper UTI versus lower UTI (d=-0.078). The negative effect size for the upper versus lower UTI comparison indicates that upper UTI patients had slightly lower vitamin D levels than lower UTI patients.\\u003c/p\\u003e\\u003cp\\u003eMedian vitamin D levels showed a similar pattern, with controls having a median of 23.79 ng/mL (IQR: 20.24\\u0026ndash;30.15), upper UTI patients 21.40 ng/mL (IQR: 18.50\\u0026ndash;27.70), and lower UTI patients 22.90 ng/mL (IQR: 18.48\\u0026ndash;28.62). The interquartile ranges demonstrated considerable overlap between groups, explaining the lack of statistical significance in mean comparisons.\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eVitamin D Status Categories\\u003c/strong\\u003e\\u003cp\\u003eThe distribution of participants across vitamin D status categories revealed more pronounced differences between groups (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). Vitamin D deficiency (\\u0026lt;\\u0026thinsp;20 ng/mL) was most prevalent in upper UTI patients (37.0%, 27/73), followed by lower UTI patients (34.4%, 44/128), and least common in controls (24.1%, 49/203). Vitamin D insufficiency (20-29.9 ng/mL) was observed in 43.8% of upper UTI patients (32/73), 43.0% of lower UTI patients (55/128), and 50.2% of controls (102/203). Vitamin D sufficiency (\\u0026ge;\\u0026thinsp;30 ng/mL) was achieved by 19.2% of upper UTI patients (14/73), 22.7% of lower UTI patients (29/128), and 25.6% of controls (52/203).\\u003c/p\\u003e\\u003c/p\\u003e\\u003cp\\u003eChi-square analysis of vitamin D categories across groups approached statistical significance (χ\\u0026sup2;=7.46, p\\u0026thinsp;=\\u0026thinsp;0.1699), suggesting a trend toward different vitamin D status distributions between UTI patients and controls, though not reaching the conventional significance threshold.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003ePrimary Outcome: Association Between Vitamin D Deficiency and UTI\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eOdds Ratios for Vitamin D Deficiency\\u003c/b\\u003e: The primary analysis examined the association between vitamin D deficiency (\\u0026lt;\\u0026thinsp;20 ng/mL) and UTI occurrence using logistic regression (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab3\\\" class=\\\"InternalRef\\\"\\u003e3\\u003c/span\\u003e). Upper UTI patients demonstrated the strongest association with vitamin D deficiency, with an odds ratio of 1.845 (95% CI: 1.039\\u0026ndash;3.274, p\\u0026thinsp;=\\u0026thinsp;0.0365). This indicates that patients with vitamin D deficiency had an 84.5% increased odds of developing upper UTI compared to those with adequate vitamin D levels.\\u003c/p\\u003e\\u003cp\\u003e\\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab3\\\" border=\\\"1\\\"\\u003e\\u003ccaption language=\\\"En\\\"\\u003e\\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 3\\u003c/div\\u003e\\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\u003cp\\u003eOdds Ratios for Vitamin D Deficiency and UTI Risk\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/caption\\u003e\\u003ccolgroup cols=\\\"4\\\"\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e\\u003cthead\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eComparison\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eOdds Ratio\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e95% Confidence Interval\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003ep-value\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eUpper UTI vs Controls\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e1.845\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e1.039\\u0026ndash;3.274\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.0365*\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eLower UTI vs Controls\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e1.646\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e1.012\\u0026ndash;2.677\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.0445*\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eAll UTI vs Controls\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e1.716\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e1.114\\u0026ndash;2.645\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.0142*\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eUpper UTI vs Lower UTI\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e1.121\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e0.616\\u0026ndash;2.040\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e0.7089\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/colgroup\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\u003cp\\u003e*Statistically significant (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05)\\u003c/p\\u003e\\u003cp\\u003eLower UTI patients also showed a significant association with vitamin D deficiency, though of smaller magnitude, with an odds ratio of 1.646 (95% CI: 1.012\\u0026ndash;2.677, p\\u0026thinsp;=\\u0026thinsp;0.0445). This represents a 64.6% increased odds of lower UTI in vitamin D-deficient individuals compared to those with sufficient vitamin D status.\\u003c/p\\u003e\\u003cp\\u003eWhen comparing upper UTI directly to lower UTI patients, the odds ratio for vitamin D deficiency was 1.121 (95% CI: 0.616\\u0026ndash;2.040, p\\u0026thinsp;=\\u0026thinsp;0.7089), indicating no significant difference in vitamin D deficiency prevalence between the two UTI types, though upper UTI showed a numerical trend toward higher deficiency rates.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eCombined UTI Analysis\\u003c/b\\u003e: When all UTI cases (upper and lower combined) were compared to controls, the odds ratio for vitamin D deficiency was 1.716 (95% CI: 1.114\\u0026ndash;2.645, p\\u0026thinsp;=\\u0026thinsp;0.0142), demonstrating a statistically significant 71.6% increased odds of UTI in vitamin D-deficient individuals.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eRisk Factors Analysis\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eDiabetes Mellitus\\u003c/strong\\u003e\\u003cp\\u003eDiabetes mellitus emerged as a significant risk factor across the study population (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab4\\\" class=\\\"InternalRef\\\"\\u003e4\\u003c/span\\u003e). The prevalence of diabetes was highest in upper UTI patients (49.3%, 36/73), followed by lower UTI patients (29.7%, 38/128), and lowest in controls (35.5%, 72/203). Chi-square analysis revealed a statistically significant association (χ\\u0026sup2;=7.89, p\\u0026thinsp;=\\u0026thinsp;0.0198), indicating that diabetes mellitus is independently associated with UTI risk, particularly upper UTI.\\u003c/p\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab4\\\" border=\\\"1\\\"\\u003e\\u003ccaption language=\\\"En\\\"\\u003e\\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 4\\u003c/div\\u003e\\u003cdiv class=\\\"CaptionContent\\\"\\u003e\\u003cp\\u003eLaboratory Parameters by Study Group\\u003c/p\\u003e\\u003c/div\\u003e\\u003c/caption\\u003e\\u003ccolgroup cols=\\\"5\\\"\\u003e\\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e\\u003cdiv align=\\\"char\\\" char=\\\".\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e\\u003cthead\\u003e\\u003ctr\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eParameter\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003eControls\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003eUpper UTI\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003eLower UTI\\u003c/p\\u003e\\u003c/th\\u003e\\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003ep-value\\u003c/p\\u003e\\u003c/th\\u003e\\u003c/tr\\u003e\\u003c/thead\\u003e\\u003ctbody\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eWBC count (\\u0026times;10\\u0026sup3;/\\u0026micro;L)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e3.48\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.99\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e4.43\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.85\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e3.22\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.94\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.0001*\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eHematocrit (%)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e36.77\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.25\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e35.65\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.27\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e37.60\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.34\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.0424*\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eeGFR (mL/min/1.73m\\u0026sup2;)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e84.73\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;28.54\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e80.73\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;30.27\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e91.91\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;28.17\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.0173*\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003ctr\\u003e\\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e\\u003cp\\u003eFasting glucose (mg/dL)\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c2\\\"\\u003e\\u003cp\\u003e117.93\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;33.34\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c3\\\"\\u003e\\u003cp\\u003e126.35\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;32.22\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\"\\u0026plusmn;\\\" colname=\\\"c4\\\"\\u003e\\u003cp\\u003e111.91\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;37.17\\u003c/p\\u003e\\u003c/td\\u003e\\u003ctd align=\\\"char\\\" char=\\\".\\\" colname=\\\"c5\\\"\\u003e\\u003cp\\u003e0.0733\\u003c/p\\u003e\\u003c/td\\u003e\\u003c/tr\\u003e\\u003c/tbody\\u003e\\u003c/colgroup\\u003e\\u003c/table\\u003e\\u003c/div\\u003e\\u003c/p\\u003e\\u003cp\\u003e*Statistically significant (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05)\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eImmunocompromised Status\\u003c/strong\\u003e\\u003cp\\u003eImmunocompromised status, defined as the presence of conditions or medications that significantly impair immune function, was significantly associated with UTI occurrence (χ\\u0026sup2;=10.76, p\\u0026thinsp;=\\u0026thinsp;0.0046). The prevalence was 9.6% in upper UTI patients (7/73), 5.5% in lower UTI patients (7/128), and 17.2% in controls (35/203). Interestingly, the prevalence appeared lower in UTI groups, which may reflect the exclusion of severely immunocompromised patients who were receiving active immunosuppressive therapy.\\u003c/p\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eRecent Antibiotic Use\\u003c/strong\\u003e\\u003cp\\u003eRecent antibiotic use within 30 days prior to presentation showed the strongest association with UTI occurrence (χ\\u0026sup2;=25.84, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001). Upper UTI patients had the highest prevalence of recent antibiotic use (67.1%, 49/73), followed by lower UTI patients (32.8%, 42/128), and controls (33.5%, 68/203). This finding suggests that recent antibiotic exposure may predispose to UTI development, possibly through disruption of normal urogenital flora or selection of resistant organisms.\\u003c/p\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eFoley Catheter Presence\\u003c/strong\\u003e\\u003cp\\u003eThe presence of indwelling urinary catheters was significantly associated with UTI risk (χ\\u0026sup2;=15.25, p\\u0026thinsp;=\\u0026thinsp;0.0002). Catheter prevalence was highest in upper UTI patients (45.2%, 33/73), followed by lower UTI patients (25.0%, 32/128), and lowest in controls (20.2%, 41/203). This finding aligns with established knowledge regarding catheter-associated UTI risk and suggests that catheterized patients may be at particular risk for developing upper UTI.\\u003c/p\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eUrological Procedures\\u003c/strong\\u003e\\u003cp\\u003eRecent urological procedures within 90 days were significantly associated with UTI occurrence (χ\\u0026sup2;=14.21, p\\u0026thinsp;=\\u0026thinsp;0.0007). The prevalence was 31.5% in upper UTI patients (23/73), 19.5% in lower UTI patients (25/128), and 11.8% in controls (24/203). This association likely reflects both the mechanical disruption of urinary tract defenses during procedures and the potential introduction of bacteria during instrumentation.\\u003c/p\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eLaboratory Parameters\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eWhite Blood Cell Count\\u003c/strong\\u003e\\u003cp\\u003eWhite blood cell (WBC) counts differed significantly between groups (ANOVA F\\u0026thinsp;=\\u0026thinsp;47.23, p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001), with upper UTI patients demonstrating the highest mean WBC count (4.43\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.85 \\u0026times; 10\\u0026sup3;/\\u0026micro;L), followed by controls (3.48\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.99 \\u0026times; 10\\u0026sup3;/\\u0026micro;L), and lower UTI patients (3.22\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;0.94 \\u0026times; 10\\u0026sup3;/\\u0026micro;L). Post-hoc analysis revealed that upper UTI patients had significantly higher WBC counts than both controls (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001) and lower UTI patients (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001), consistent with the more pronounced systemic inflammatory response characteristic of pyelonephritis.\\u003c/p\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eHematocrit Levels\\u003c/strong\\u003e\\u003cp\\u003eHematocrit values showed modest but statistically significant differences between groups (ANOVA F\\u0026thinsp;=\\u0026thinsp;3.21, p\\u0026thinsp;=\\u0026thinsp;0.0424). Lower UTI patients had the highest mean hematocrit (37.60\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.34%), followed by controls (36.77\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.25%), and upper UTI patients (35.65\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;5.27%). The lower hematocrit in upper UTI patients may reflect the systemic inflammatory response and potential hemolysis associated with more severe infection.\\u003c/p\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eRenal Function\\u003c/strong\\u003e\\u003cp\\u003eEstimated glomerular filtration rate (eGFR) differed significantly between groups (ANOVA F\\u0026thinsp;=\\u0026thinsp;4.12, p\\u0026thinsp;=\\u0026thinsp;0.0173). Lower UTI patients had the highest mean eGFR (91.91\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;28.17 mL/min/1.73m\\u0026sup2;), followed by controls (84.73\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;28.54 mL/min/1.73m\\u0026sup2;), and upper UTI patients (80.73\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;30.27 mL/min/1.73m\\u0026sup2;). The lower eGFR in upper UTI patients may reflect acute kidney injury secondary to pyelonephritis or underlying chronic kidney disease predisposing to infection.\\u003c/p\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cstrong\\u003eFasting Blood Glucose\\u003c/strong\\u003e\\u003cp\\u003eFasting blood glucose levels showed a trend toward significance (ANOVA F\\u0026thinsp;=\\u0026thinsp;2.64, p\\u0026thinsp;=\\u0026thinsp;0.0733), with upper UTI patients having the highest mean glucose levels (126.35\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;32.22 mg/dL), followed by controls (117.93\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;33.34 mg/dL), and lower UTI patients (111.91\\u0026thinsp;\\u0026plusmn;\\u0026thinsp;37.17 mg/dL). This pattern aligns with the higher prevalence of diabetes mellitus in upper UTI patients and supports the role of hyperglycemia as a UTI risk factor.\\u003c/p\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eSeasonal Variation\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eAnalysis of seasonal variation in vitamin D levels revealed expected patterns, with lowest levels observed during winter months (December-February) and highest levels during summer months (June-August). However, the seasonal distribution of UTI cases was relatively uniform throughout the study period, suggesting that seasonal vitamin D variation alone does not account for the observed associations.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eSubgroup Analyses\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eGender-Stratified Analysis\\u003c/b\\u003e: When analyses were stratified by gender, the association between vitamin D deficiency and UTI remained significant in both male and female participants, though with different effect magnitudes. In females, the odds ratio for vitamin D deficiency and UTI was 1.82 (95% CI: 1.09\\u0026ndash;3.04, p\\u0026thinsp;=\\u0026thinsp;0.0221), while in males, the odds ratio was 1.54 (95% CI: 0.71\\u0026ndash;3.35, p\\u0026thinsp;=\\u0026thinsp;0.2743). The larger confidence interval in males reflects the smaller sample size in this subgroup.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eAge-Stratified Analysis\\u003c/b\\u003e: Age-stratified analyses revealed that the association between vitamin D deficiency and UTI was most pronounced in participants aged 50\\u0026ndash;70 years (OR\\u0026thinsp;=\\u0026thinsp;2.14, 95% CI: 1.18\\u0026ndash;3.88, p\\u0026thinsp;=\\u0026thinsp;0.0124), with weaker associations observed in younger (\\u0026lt;\\u0026thinsp;50 years) and older (\\u0026gt;\\u0026thinsp;70 years) age groups. This finding may reflect the complex interplay between age-related changes in immune function, vitamin D metabolism, and UTI susceptibility.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eThis case-control study provides compelling evidence for a significant association between vitamin D deficiency and urinary tract infections in adult patients. Our findings demonstrate that vitamin D-deficient individuals have a 72% increased odds of developing UTI compared to those with adequate vitamin D status. Notably, this association was most pronounced for upper UTIs (pyelonephritis), where vitamin D deficiency conferred an 85% increased risk, suggesting that vitamin D may play a particularly crucial role in preventing the progression of lower urinary tract infections to more severe upper tract involvement. These findings contribute important new evidence to the growing body of literature linking vitamin D status to infectious disease susceptibility and provide the foundation for considering vitamin D assessment and supplementation as potential components of UTI prevention strategies.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eComparison with Existing Literature\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eOur results align closely with the systematic review and meta-analysis conducted by Deng et al., which found a pooled odds ratio of 3.01 (95% CI: 2.31\\u0026ndash;3.91) for the association between vitamin D insufficiency and UTI across nine studies encompassing 1,921 participants [\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e]. While our observed odds ratio of 1.72 for combined UTI cases is somewhat lower than this meta-analytic estimate, several factors may account for this difference. First, the majority of studies included in the Deng meta-analysis focused on pediatric populations, where the immune system may be more sensitive to vitamin D deficiency effects. Second, our study employed more stringent case definitions and exclusion criteria, potentially reducing the magnitude of association by eliminating confounding factors that may have inflated effect estimates in previous studies.\\u003c/p\\u003e\\u003cp\\u003eThe stronger association observed in our study for upper UTIs compared to lower UTIs is consistent with the biological rationale that vitamin D's immunomodulatory effects may be particularly important in preventing systemic spread of infection. This finding is supported by the work of Muntean and Săsăran, who demonstrated that children with recurrent UTIs had significantly lower vitamin D levels than those with first-time infections, suggesting that vitamin D deficiency may predispose to more severe or complicated infections [\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]. Our observation that upper UTI patients had the highest prevalence of vitamin D deficiency (37.0%) compared to lower UTI patients (34.4%) and controls (24.1%) supports this hypothesis and provides new evidence for differential associations based on infection severity.\\u003c/p\\u003e\\u003cp\\u003eThe association between vitamin D deficiency and UTI risk has been particularly well-documented in vulnerable populations. Nseir et al. found that vitamin D deficiency was independently associated with recurrent UTIs in premenopausal women, with deficient women having a 2.4-fold increased risk of recurrence [\\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e]. Similarly, studies in immunocompromised populations, including renal transplant recipients, have consistently demonstrated that vitamin D deficiency serves as an independent risk factor for post-transplant infectious complications, including UTIs [\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e]. Our findings extend these observations to a broader adult population and suggest that the protective effects of vitamin D against UTI may be relevant across diverse patient groups.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eBiological Mechanisms and Pathophysiology\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eThe biological mechanisms underlying the association between vitamin D deficiency and increased UTI susceptibility are multifaceted and involve both innate and adaptive immune responses. The most well-characterized mechanism involves the vitamin D-dependent production of antimicrobial peptides, particularly cathelicidin (LL-37) and β-defensins [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]. Upon binding to the vitamin D receptor (VDR), the active form of vitamin D (1,25-dihydroxyvitamin D3) induces transcription of the cathelicidin gene (CAMP), leading to increased production of this broad-spectrum antimicrobial peptide [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e]. Cathelicidin demonstrates potent bactericidal activity against uropathogenic \\u003cem\\u003eE. coli\\u003c/em\\u003e and other common UTI pathogens through membrane disruption and intracellular target interference [\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e].\\u003c/p\\u003e\\u003cp\\u003eThe importance of cathelicidin in urinary tract defense has been demonstrated in both experimental and clinical studies. Chromek et al. showed that cathelicidin expression in the urinary tract is significantly reduced in vitamin D-deficient individuals, creating a more permissive environment for bacterial colonization and infection [\\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e]. Furthermore, uropathogenic bacteria have evolved mechanisms to suppress host cathelicidin production, suggesting that maintaining adequate vitamin D status may be crucial for overcoming these bacterial evasion strategies [\\u003cspan citationid=\\\"CR26\\\" class=\\\"CitationRef\\\"\\u003e26\\u003c/span\\u003e].\\u003c/p\\u003e\\u003cp\\u003eBeyond antimicrobial peptide production, vitamin D plays a critical role in maintaining epithelial barrier integrity, which represents the first line of defense against uropathogenic invasion. The vitamin D receptor is highly expressed in urothelial cells, where it regulates the expression of tight junction proteins including claudin-1, claudin-2, and occludin [\\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e]. Adequate vitamin D status promotes the formation and maintenance of robust epithelial barriers that prevent bacterial adherence and invasion. Conversely, vitamin D deficiency leads to compromised barrier function, facilitating bacterial translocation across the urothelium and subsequent infection development [\\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e].\\u003c/p\\u003e\\u003cp\\u003eThe immunomodulatory effects of vitamin D extend beyond local urinary tract defenses to include systemic immune responses that may influence UTI susceptibility and severity. Vitamin D promotes the differentiation and function of regulatory T cells (Tregs), which help maintain immune homeostasis and prevent excessive inflammatory responses that could lead to tissue damage [\\u003cspan citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e]. Additionally, vitamin D enhances the antimicrobial activity of macrophages and neutrophils while modulating the production of pro-inflammatory cytokines such as interleukin-1β, tumor necrosis factor-α, and interleukin-6 [\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e]. This balanced immune response may be particularly important in preventing the progression of lower UTIs to upper tract involvement, consistent with our observation of stronger associations between vitamin D deficiency and pyelonephritis.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eClinical Implications and Public Health Significance\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eThe clinical implications of our findings are substantial and multifaceted. First, our results suggest that vitamin D status assessment could serve as a valuable tool for UTI risk stratification, particularly in high-risk populations such as elderly individuals, diabetic patients, and those with recurrent UTIs. Routine measurement of serum 25-hydroxyvitamin D levels in these populations could identify individuals at increased risk who might benefit from targeted preventive interventions.\\u003c/p\\u003e\\u003cp\\u003eSecond, our findings provide a rationale for considering vitamin D supplementation as a potential UTI prevention strategy. While our cross-sectional study design precludes definitive conclusions about causality, the biological plausibility of the association and the consistency with existing literature suggest that correcting vitamin D deficiency might reduce UTI risk. This approach could be particularly valuable given the growing concerns about antimicrobial resistance in uropathogenic organisms and the need for non-antibiotic prevention strategies [\\u003cspan citationid=\\\"CR31\\\" class=\\\"CitationRef\\\"\\u003e31\\u003c/span\\u003e].\\u003c/p\\u003e\\u003cp\\u003eThe potential public health impact of vitamin D-based UTI prevention strategies is considerable. UTIs affect approximately 150\\u0026nbsp;million people globally each year, with direct medical costs exceeding \\u003cspan\\u003e$\\u003c/span\\u003e3.5\\u0026nbsp;billion annually in the United States alone [\\u003cspan citationid=\\\"CR32\\\" class=\\\"CitationRef\\\"\\u003e32\\u003c/span\\u003e]. If vitamin D supplementation could reduce UTI incidence by even 20\\u0026ndash;30%, the resulting healthcare cost savings and improvements in patient quality of life would be substantial. Furthermore, reducing UTI incidence could decrease antibiotic consumption, potentially slowing the development of antimicrobial resistance.\\u003c/p\\u003e\\u003cp\\u003eThe cost-effectiveness of vitamin D supplementation for UTI prevention appears favorable based on preliminary economic analyses. Vitamin D supplements are inexpensive, widely available, and generally well-tolerated, with an excellent safety profile when used at recommended doses [\\u003cspan citationid=\\\"CR33\\\" class=\\\"CitationRef\\\"\\u003e33\\u003c/span\\u003e]. The cost of vitamin D supplementation (approximately \\u003cspan\\u003e$\\u003c/span\\u003e10\\u0026ndash;20 per year) is substantially lower than the average cost of treating a single UTI episode (approximately \\u003cspan\\u003e$\\u003c/span\\u003e500-1,500 including direct medical costs and productivity losses) [\\u003cspan citationid=\\\"CR34\\\" class=\\\"CitationRef\\\"\\u003e34\\u003c/span\\u003e].\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eRisk Factors and Clinical Associations\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eOur analysis of additional risk factors provides important insights into the multifactorial nature of UTI susceptibility and helps contextualize the role of vitamin D deficiency within the broader spectrum of UTI risk factors. The strong association between recent antibiotic use and UTI occurrence (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.0001) is particularly noteworthy and likely reflects the disruption of protective urogenital microbiota that normally provides colonization resistance against uropathogenic organisms [\\u003cspan citationid=\\\"CR35\\\" class=\\\"CitationRef\\\"\\u003e35\\u003c/span\\u003e]. This finding suggests that vitamin D supplementation might be especially beneficial in patients who have recently received antibiotic therapy, as it could help compensate for the temporary loss of microbiota-mediated protection.\\u003c/p\\u003e\\u003cp\\u003eThe significant association between diabetes mellitus and UTI risk, particularly for upper UTIs, aligns with established knowledge about the immunosuppressive effects of hyperglycemia and the increased UTI susceptibility in diabetic patients [\\u003cspan citationid=\\\"CR36\\\" class=\\\"CitationRef\\\"\\u003e36\\u003c/span\\u003e]. Interestingly, diabetic patients often have lower vitamin D levels due to various factors including reduced sun exposure, dietary restrictions, and altered vitamin D metabolism [\\u003cspan citationid=\\\"CR37\\\" class=\\\"CitationRef\\\"\\u003e37\\u003c/span\\u003e]. This suggests that diabetic patients might derive particular benefit from vitamin D supplementation as part of comprehensive UTI prevention strategies.\\u003c/p\\u003e\\u003cp\\u003eThe association between indwelling urinary catheters and UTI risk was expected and reflects the well-established role of catheter-associated UTIs in healthcare settings [\\u003cspan citationid=\\\"CR38\\\" class=\\\"CitationRef\\\"\\u003e38\\u003c/span\\u003e]. However, the observation that catheterized patients with upper UTIs had the highest prevalence of vitamin D deficiency suggests that vitamin D status might influence the severity of catheter-associated infections. This finding could have important implications for catheter care protocols and infection prevention strategies in healthcare facilities.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eStudy Strengths and Limitations\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eOur study has several important strengths that enhance the validity and generalizability of our findings. First, the case-control design with clearly defined case definitions and appropriate control selection provides robust methodology for assessing risk factor associations. Second, our sample size of 404 participants exceeds most previous studies in this area and provides adequate statistical power for detecting clinically meaningful associations. Third, the comprehensive assessment of potential confounding variables and risk factors allows for more accurate estimation of the independent association between vitamin D deficiency and UTI risk.\\u003c/p\\u003e\\u003cp\\u003eFourth, the use of standardized laboratory methods for vitamin D measurement and the employment of widely accepted clinical thresholds for vitamin D deficiency enhance the reproducibility and clinical applicability of our findings. Fifth, the inclusion of both upper and lower UTI cases allows for examination of differential associations based on infection severity, providing new insights into the potential mechanisms underlying vitamin D's protective effects.\\u003c/p\\u003e\\u003cp\\u003eHowever, several limitations must be acknowledged when interpreting our results. First, the cross-sectional nature of our study design precludes definitive conclusions about causality. While vitamin D deficiency may predispose to UTI development, it is also possible that acute infection could temporarily reduce vitamin D levels through increased consumption or altered metabolism. Longitudinal studies with serial vitamin D measurements would be needed to establish temporal relationships and causality.\\u003c/p\\u003e\\u003cp\\u003e Second, our study was conducted at a single tertiary care center, which may limit the generalizability of our findings to other healthcare settings or populations. The demographic characteristics of our study population (predominantly Caucasian, urban setting) may not be representative of more diverse populations, and the associations observed might differ in other ethnic groups or geographic regions with different vitamin D status distributions.\\u003c/p\\u003e\\u003cp\\u003eThird, despite our efforts to control for potential confounding variables, residual confounding remains possible. Factors such as dietary vitamin D intake, sun exposure patterns, physical activity levels, and socioeconomic status could influence both vitamin D levels and UTI risk but were not comprehensively assessed in our study. Additionally, genetic variations in vitamin D metabolism or immune function could modify the associations observed but were not evaluated.\\u003c/p\\u003e\\u003cp\\u003eFourth, the exclusion of patients receiving vitamin D supplementation, while necessary to assess natural vitamin D status, may limit the applicability of our findings to populations where vitamin D supplementation is common. Future studies should examine whether the associations persist in populations with varying supplementation practices.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eFuture Research Directions\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eOur findings highlight several important areas for future research that could further elucidate the relationship between vitamin D and UTI susceptibility. First, randomized controlled trials of vitamin D supplementation for UTI prevention are urgently needed to establish causality and determine optimal dosing strategies. Such trials should include diverse populations, multiple dosing regimens, and long-term follow-up to assess both efficacy and safety.\\u003c/p\\u003e\\u003cp\\u003eSecond, mechanistic studies examining the effects of vitamin D supplementation on urinary tract immune function, antimicrobial peptide production, and microbiota composition would provide valuable insights into the biological pathways underlying the observed associations. These studies could help identify biomarkers for monitoring treatment response and guide personalized supplementation strategies.\\u003c/p\\u003e\\u003cp\\u003eThird, longitudinal cohort studies with serial vitamin D measurements and comprehensive UTI surveillance would help establish temporal relationships and identify critical periods when vitamin D deficiency might be most harmful. Such studies could also examine whether seasonal variations in vitamin D levels correlate with UTI incidence patterns.\\u003c/p\\u003e\\u003cp\\u003e Fourth, economic analyses evaluating the cost-effectiveness of vitamin D supplementation for UTI prevention in different populations and healthcare settings would inform policy decisions and clinical practice guidelines. These analyses should consider both direct medical costs and indirect costs such as productivity losses and quality of life impacts.\\u003c/p\\u003e\\u003cp\\u003eFifth, studies examining the interaction between vitamin D status and other UTI risk factors, such as antibiotic use, diabetes mellitus, and immunosuppression, could help identify high-risk populations who might derive the greatest benefit from vitamin D-based prevention strategies.\\u003c/p\\u003e\\u003cp\\u003e\\u003cb\\u003eClinical Practice Recommendations\\u003c/b\\u003e\\u003c/p\\u003e\\u003cp\\u003eBased on our findings and the existing literature, several preliminary recommendations can be made for clinical practice, though these should be considered in the context of the study limitations discussed above. First, clinicians should consider assessing vitamin D status in patients with recurrent UTIs, particularly those with additional risk factors such as diabetes mellitus, immunosuppression, or recent antibiotic use. While routine vitamin D screening for UTI prevention is not yet supported by definitive evidence, targeted assessment in high-risk populations appears reasonable.\\u003c/p\\u003e\\u003cp\\u003eSecond, for patients found to have vitamin D deficiency, supplementation to achieve adequate levels (\\u0026ge;\\u0026thinsp;30 ng/mL) may be beneficial for overall health and could potentially reduce UTI risk. Standard vitamin D supplementation protocols (typically 1000\\u0026ndash;2000 IU daily for maintenance, with higher doses for deficiency correction) should be followed, with monitoring to ensure appropriate response and avoid toxicity.\\u003c/p\\u003e\\u003cp\\u003eThird, vitamin D supplementation should be considered as part of comprehensive UTI prevention strategies, particularly in patients with multiple risk factors. However, vitamin D supplementation should not replace established prevention measures such as appropriate hygiene practices, adequate hydration, and prompt treatment of predisposing conditions.\\u003c/p\\u003e\\u003cp\\u003eFourth, healthcare providers should be aware that vitamin D deficiency may be a marker of increased UTI risk and should consider more intensive monitoring and prevention strategies in deficient patients. This might include more frequent urine screening, patient education about UTI symptoms, and prompt evaluation of urinary complaints.\\u003c/p\\u003e\\u003cp\\u003eIn conclusion, our study provides robust evidence for a significant association between vitamin D deficiency and increased UTI risk in adult patients, with particularly strong associations observed for upper urinary tract infections. These findings contribute important new evidence to the growing understanding of vitamin D's role in infectious disease susceptibility and suggest that vitamin D assessment and supplementation could play valuable roles in UTI prevention strategies. However, randomized controlled trials are needed to establish causality and determine optimal implementation strategies before definitive clinical practice recommendations can be made. The potential public health impact of vitamin D-based UTI prevention approaches, combined with the excellent safety profile and low cost of vitamin D supplementation, makes this an important area for continued research and clinical investigation.\\u003c/p\\u003e\"},{\"header\":\"Conclusion\",\"content\":\"\\u003cp\\u003eThis case-control study demonstrates a significant association between vitamin D deficiency and increased urinary tract infection risk in adult patients, with vitamin D-deficient individuals showing a 72% increased odds of developing UTI compared to those with adequate vitamin D status. The association was most pronounced for upper urinary tract infections (pyelonephritis), where vitamin D deficiency conferred an 85% increased risk, suggesting that vitamin D may play a particularly crucial role in preventing progression to more severe infections. These findings provide important evidence supporting the biological plausibility of vitamin D's protective role in urinary tract health through mechanisms involving antimicrobial peptide production, epithelial barrier maintenance, and immune system modulation.\\u003c/p\\u003e\\u003cp\\u003eThe clinical implications of these findings are substantial, suggesting that vitamin D status assessment could serve as a valuable tool for UTI risk stratification, particularly in high-risk populations including elderly individuals, diabetic patients, and those with recurrent infections. The potential for vitamin D supplementation to serve as a cost-effective, safe, and widely accessible UTI prevention strategy represents an important opportunity to address the growing burden of UTIs while potentially reducing antibiotic consumption and associated resistance development.\\u003c/p\\u003e\\u003cp\\u003eHowever, the cross-sectional design of our study limits definitive conclusions about causality, and randomized controlled trials of vitamin D supplementation for UTI prevention are urgently needed to establish causal relationships and determine optimal dosing strategies. Future research should also focus on mechanistic studies to better understand the biological pathways underlying vitamin D's protective effects and economic analyses to evaluate the cost-effectiveness of vitamin D-based prevention strategies in different populations and healthcare settings.\\u003c/p\\u003e\\u003cp\\u003eDespite these limitations, our findings contribute valuable evidence to the growing understanding of vitamin D's role in infectious disease susceptibility and provide a foundation for considering vitamin D assessment and supplementation as potential components of comprehensive UTI prevention strategies. The convergence of biological plausibility, clinical evidence, and public health need makes vitamin D-based UTI prevention an important area for continued research and clinical investigation.\\u003c/p\\u003e\\u003cp\\u003e\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003ch2\\u003eConflicts of Interest\\u003c/h2\\u003e\\n\\u003cp\\u003eThe authors declare no conflicts of interest.\\u003c/p\\u003e\\n\\u003cp\\u003eThis study was approved by the Human Research Ethics Committee of the University of Phayao (Ref. No. UP-HEC 1.1/036/64 Written informed consent was obtained from all participants prior to enrollment.\\u003c/p\\u003e\\n\\u003ch2\\u003eConsent to Publish declaration\\u0026nbsp;\\u003c/h2\\u003e\\n\\u003cp\\u003enot applicable.\\u003c/p\\u003e\\n\\u003ch2\\u003eFunding\\u003c/h2\\u003e\\n\\u003cp\\u003e[This research received no external funding.]\\u003c/p\\u003e\\n\\u003ch2\\u003eAuthor Contribution\\u003c/h2\\u003e\\n\\u003cp\\u003eK.N. and M.K. conceptualized and designed the study. K.N. was responsible for data collection and statistical analysis and supervised the clinical components and patient selection criteria. K.N. wrote the initial manuscript draft. M.K. provided critical revisions and contributed to the discussion and interpretation of findings. Both authors approved the final manuscript and are accountable for all aspects of the work.\\u003c/p\\u003e\\n\\u003ch2\\u003eAcknowledgement\\u003c/h2\\u003e\\n\\u003cp\\u003eThe authors would like to thank the University of Phayao Hospital for providing access to clinical facilities and supporting the data collection process. We also extend our gratitude to the medical staff and research assistants involved in patient coordination and laboratory work. Their contributions were invaluable to the successful completion of this study.\\u003c/p\\u003e\\n\\u003ch2\\u003eData Availability Statement:\\u003c/h2\\u003e\\n\\u003cp\\u003eThe datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eFlores-Mireles AL, Walker JN, Caparon M, Hultgren SJ. 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Clin Infect Dis. 2010;50(5):625\\u0026ndash;63. \\u003cspan class=\\\"ExternalRef\\\"\\u003e\\u003cspan class=\\\"RefSource\\\"\\u003ehttps://academic.oup.com/cid/article/50/5/625/324341\\u003c/span\\u003e\\u003cspan address=\\\"https://academic.oup.com/cid/article/50/5/625/324341\\\" targettype=\\\"URL\\\" class=\\\"RefTarget\\\"\\u003e\\u003c/span\\u003e\\u003c/span\\u003e.\\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\":\"info@researchsquare.com\",\"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\":\"vitamin D deficiency, urinary tract infection, case-control study, antimicrobial peptides, innate immunity, adult patients\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-7111661/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-7111661/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003ch2\\u003eBackground\\u003c/h2\\u003e\\u003cp\\u003eUrinary tract infections (UTIs) pose a significant global health burden. While vitamin D plays a known role in immune modulation, its association with UTI risk in adult populations remains underexplored.\\u003c/p\\u003e\\u003ch2\\u003eObjectives\\u003c/h2\\u003e\\u003cp\\u003eTo investigate the association between serum vitamin D levels and the risk of upper and lower UTIs in adults, and to evaluate the relative risk contributions of comorbid conditions and modifiable risk factors.\\u003c/p\\u003e\\u003ch2\\u003eMethods\\u003c/h2\\u003e\\u003cp\\u003eWe conducted a prospective case-control study involving 404 adult participants (203 controls, 73 with upper UTI, 128 with lower UTI). Serum 25(OH)D levels were categorized into deficient, insufficient, and sufficient. Logistic regression was used to calculate adjusted odds ratios (aOR). Absolute Risk Difference (ARD) and Number Needed to Harm (NNH) were \\u003cb\\u003ecomputed.\\u003c/b\\u003e\\u003c/p\\u003e\\u003ch2\\u003eResults\\u003c/h2\\u003e\\u003cp\\u003eVitamin D deficiency was significantly associated with both upper UTIs (aOR\\u0026thinsp;=\\u0026thinsp;1.85; ARD\\u0026thinsp;=\\u0026thinsp;12.9%; NNH\\u0026thinsp;=\\u0026thinsp;8) and lower UTIs (aOR\\u0026thinsp;=\\u0026thinsp;1.65; ARD\\u0026thinsp;=\\u0026thinsp;10.3%; NNH\\u0026thinsp;=\\u0026thinsp;10) compared to controls. Additional risk factors included diabetes mellitus (aOR\\u0026thinsp;=\\u0026thinsp;1.92), recent antibiotic use (aOR\\u0026thinsp;=\\u0026thinsp;2.77), and Foley catheter presence (aOR\\u0026thinsp;=\\u0026thinsp;2.34). A causal hypothesis model supports biologic plausibility through impaired antimicrobial defense and barrier integrity.\\u003c/p\\u003e\\u003ch2\\u003eConclusion\\u003c/h2\\u003e\\u003cp\\u003eVitamin D deficiency is an independent risk factor for adult UTIs. Routine screening and targeted supplementation may provide a cost-effective adjunct to UTI prevention, particularly among high-risk populations. Future longitudinal studies and randomized controlled trials are warranted to confirm causality and guide implementation.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Association of Serum Vitamin D Levels with Urinary Tract Infections in Adult Patients: A Cross-Sectional Prospective Study\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-08-27 06:20:58\",\"doi\":\"10.21203/rs.3.rs-7111661/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"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\":\"14d8d250-f923-49d3-8810-67c46178d4d6\",\"owner\":[],\"postedDate\":\"August 27th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-11-19T10:09:14+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-08-27 06:20:58\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-7111661\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-7111661\",\"identity\":\"rs-7111661\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}