Procalcitonin in predicting acute kidney damage in children with initial febrile urinary tract infection: a retrospective study

Introduction

Urinary tract infections (UTIs) are among the most prevalent bacterial infections in childhood, with Escherichia coli accounting for approximately 80% of cases (1). A global meta‑analysis published in 2023, encompassing 36 studies, reported an overall UTI prevalence of 15% in children, with a notable gender difference (16% in girls vs. 10% in boys) (2). Approximately 8% of girls and 2% of boys develop UTIs by the age of 7 years (1). A severe and well-recognized complication of UTIs is renal parenchymal injury. Approximately 10–15% of children develop irreversible renal scarring following an initial febrile UTI (3), which has been proven to be an independent risk factor for hypertension, chronic kidney disease (CKD), and end-stage renal disease (4). Furthermore, UTIs are accompanied by a considerable recurrence risk. In young infants, the one-year recurrence rate after an initial UTI is 12.2% (5). This risk escalates in vulnerable populations, with one study indicating that 54% of children with a history of acute pyelonephritis suffer from subsequent UTI episodes (6). More importantly, recurrent UTIs serve as a key contributor to long-term renal morbidity. The incidence of renal scarring after a single febrile UTI is estimated to range from 2.8% to 15% (7). However, this risk increases substantially with each recurrent infection, and meta-analyses have demonstrated that approximately one-third of children with recurrent febrile UTIs eventually develop renal scarring (8). In patients with vesicoureteral reflux (VUR), the risk of renal scarring rises sharply alongside repeated infections, with incidence rates of 26% in non-recurrent cases, 38% after a single recurrence, and up to 80% after multiple recurrent episodes, respectively (9). Previous studies have demonstrated that early intervention for acute kidney damage can prevent progression to permanent damage or renal scarring (7,10,11).

Technetium-99m labelled dimercaptosuccinic acid (^99mTc-DMSA) scintigraphy is considered the gold standard for assessing renal cortical integrity and diagnosing acute or chronic kidney damage (4,12). A visual scoring system based on ^99mTc-DMSA scintigraphy was associated with frequent recurrences, short recurrence intervals, and risk stratification in pediatric patients with UTIs (13). In routine clinical practice, early ^99mTc-DMSA scintigraphy conducted within the first week of admission has become a common empirical approach for hospitalized children with febrile UTI in multiple medical centers, including our institution. Nevertheless, this early one-week imaging strategy is not standardized nor endorsed by international clinical guidelines, and its clinical necessity and additional diagnostic value remain widely debated in the literature (14). Widespread empirical ^99mTc-DMSA utilization has raised considerable clinical concerns (4,12), including unnecessary over-imaging and increased medical costs. Of major concern is the cumulative low-dose radiation burden in the pediatric population, a group uniquely susceptible to ionizing radiation. Moreover, the requirement for specialized nuclear medicine equipment substantially limits the accessibility of ^99mTc-DMSA scintigraphy, particularly in primary care and resource-limited settings. Accurate identification of individuals at high risk for acute kidney damage following a first UTI, followed by prompt and appropriate therapy, can significantly improve clinical outcomes.

The 2011 American Academy of Pediatrics (AAP) guideline, reaffirmed in 2016, remains widely referenced in clinical practice (15). It recommends that all infants with febrile UTI undergo renal and bladder ultrasonography (RBUS). However, numerous studies have confirmed that RBUS cannot accurately predict renal damage (16). The 2011 AAP guideline also states that voiding cystourethrography (VCUG) should not be performed routinely; it is indicated only when RBUS reveals hydronephrosis, renal scarring, findings suggestive of high-grade VUR, or obstructive uropathy. Therefore, although many previous studies have shown that high-grade VUR is a predictor of renal injury after UTI (5,17), not all patients undergo VCUG in clinical practice. Thus, identifying readily accessible clinical or biochemical markers during the acute phase of a febrile UTI that are associated with acute kidney damage would be of significant clinical value. Several meta-analyses, including a 2020 Cochrane review and a 2025 systematic review, have confirmed that procalcitonin (PCT) demonstrates superior diagnostic accuracy for acute pyelonephritis compared with C-reactive protein (CRP) and other inflammatory markers (18,19). However, these aggregated analyses did not derive a clinically actionable PCT threshold against the gold-standard endpoint of DMSA-confirmed acute kidney damage. Moreover, the Cochrane review explicitly concluded that there is “no compelling evidence to recommend the routine use of any of these tests in clinical practice” (18), and the 2025 meta-analysis called for additional primary studies to explore the role of biomarkers in this setting (19).

Therefore, the present study aimed to directly compare multiple inflammatory markers for predicting ^99mTc-DMSA-confirmed acute kidney damage in children with a first febrile UTI, to identify an optimal cutoff value with high sensitivity and specificity, and to propose a practical triage strategy applicable in primary care settings without gamma camera equipment. We present this article in accordance with the STARD reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0179/rc).

Methods

Study design and participants

This retrospective study enrolled pediatric patients aged <18 years who were hospitalized with febrile UTIs at the Department of Pediatrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, between January 2023 and May 2023. Consecutive sampling was adopted for participant recruitment. Clinical data were retrospectively extracted from the electronic medical record system by two trained researchers through manual review, and any discrepancies were resolved by consensus.

Ethical statement

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University (No. 2024-K-339-01) and individual consent for this retrospective analysis was waived.

Inclusion and exclusion criteria

Patients were enrolled according to the criteria outlined in the 2011 AAP Clinical Practice Guideline (reaffirmed in 2016) (15). All of the following inclusion criteria must be met simultaneously: (I) high fever with a documented axillary temperature ≥38 ℃ measured and recorded by medical staff at admission. Fever based solely on parental recall was excluded; (II) pyuria, defined as >5 white blood cells (WBCs) per high-power field on microscopy, or a positive leukocyte esterase or nitrite test on urinalysis; (III) significant bacteriuria, defined as urine culture yielding ≥10⁵ CFU/mL of a single uropathogen (Note: details regarding urine collection are described in the “Urine Sample Collection and Processing” section below); (IV) no other identifiable source of infection to explain the fever.

Children were excluded if they met any of the following criteria: temperature <38 ℃, prior UTI, previous kidney surgeries, known renal abnormalities (e.g., ectopic ureter, ureterocele, posterior urethral valve, neurogenic bladder, solitary kidney), or polymicrobial bacteriuria (growth of ≥2 organisms). were excluded.

Urine sample collection and processing

To mitigate the risk of specimen contamination, a standardized urine collection protocol was strictly implemented for all study participants in this retrospective cohort study. For pediatric subjects aged ≥24 months, urine specimens were acquired via clean-catch midstream voiding, a standard non-invasive sampling technique. In contrast, sterile adhesive urine collection bags were employed for infants and toddlers aged <24 months, who were mostly diapered. Prior to specimen acquisition, all participants underwent standardized perineal cleansing with sterile normal saline, followed by thorough air-drying to avoid residual moisture-induced contamination. All urine specimens were transported to the clinical microbiology laboratory within 1–2 hours of collection for routine urinalysis and bacterial culture. Specimens with polymicrobial growth, a well-recognized indicator of pre-analytical contamination, were systematically excluded from the final analysis to ensure the integrity and reliability of the study data.

Clinical and laboratory data collection

All the enrolled children received a complete blood count test, urinalysis, CRP, and PCT test within 24 hours of admission. Basic information recorded included gender, age (in months or years), highest documented temperature, and delayed time—defined as the time interval (in hours) between the first fever symptom and hospital admission. Main inflammatory markers recorded were WBC count, absolute neutrophil count, neutrophil percentage (NEUT%, the percentage of neutrophils in peripheral WBC), CRP and PCT.

^99mTc-DMSA scintigraphy and definition of acute kidney damage

Renal scintigraphy using ^99mTc-DMSA was performed within one week after admission. Each patient received a weight-adjusted intravenous dose of ^99mTc-DMSA (minimum 1 mCi, maximum 5 mCi) (18). Imaging was conducted 1.5 hours post-injection using a single-photon emission computed tomography scanner (Symbia Intevo Bold, Siemens Medical Systems, Erlangen, Germany) equipped with a low-energy high-resolution parallel-hole collimator, centered on the 140 keV photopeak with a 20% symmetric energy window. The matrix size was 128×128 or 256×256.

All scans were evaluated independently by two experienced nuclear medicine physicians who were blinded to the children’s clinical data; disagreements were resolved by consensus. Acute kidney damage was defined as the presence of one or more focal or diffuse areas of decreased or absent radiotracer uptake (photopenia) in the renal cortex, which represents acute inflammatory changes. Importantly, such acute inflammatory cortical lesions are potentially reversible and should not be equated with irreversible, permanent renal scarring. According to the initial acute-phase ^99mTc-DMSA findings, all enrolled children were categorized into a normal group and an acute kidney damage group. Notably, follow-up ^99mTc-DMSA imaging was not routinely performed in our cohort; therefore, we could not further differentiate transient inflammatory lesions from chronic permanent renal scarring.

Statistical analysis

All statistical analyses were performed using SPSS version 23.0 (IBM Corp., Armonk, NY, USA). Normally distributed continuous variables were expressed as mean ± standard deviation (SD), while non-normally distributed variables were reported as median with interquartile range (IQR; P25–P75). Categorical variables were presented as frequencies (percentages). For between-group comparisons. the independent-samples t-test was used for normally distributed continuous data, the Mann-Whitney U test for non-normally distributed continuous data, and the chi-square test or Fisher’s exact test for categorical variables, as appropriate. Univariate logistic regression was performed to identify potential factors associated with acute kidney damage. Subsequently, a multivariate logistic regression model incorporating delayed time, CRP, WBC, absolute neutrophil count and PCT was established to identify independent predictors of acute kidney damage. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive performance of the model. A post hoc power analysis was conducted based on the primary results. A two-sided P value <0.05 was considered statistically significant.

Results

Of the 244 consecutive pediatric patients aged <18 years hospitalized with UTIs at The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University from January 2023 to May 2023, those with afebrile UTI (n=13), recurrent UTI (n=67), renal duplication (n=4), and renal dysplasia (n=3) were excluded. Among the remaining patients, 30 underwent VCUG for clinical assessment, and 14 were diagnosed with VUR. These 14 VUR-positive children were further excluded from the final analysis. Ultimately, 143 participants met the inclusion criteria (Figure 1), comprising 66 boys and 77 girls, with a median age of 7.0 months (range, 1 month to 12 years) and a male-to-female ratio of 1:1.17. Among these children, 126 (88.11%) were younger than 24 months of age. All male participants in this study were uncircumcised. The majority of included patients (95.8%) presented with fever exceeding 38.5 ℃. Peripheral inflammatory biomarkers, including CRP, WBC count, neutrophil percentage, absolute neutrophil count, and PCT, were markedly elevated compared with normal reference ranges (Table 1). Urine culture results of the 143 eligible participants showed that 124 cases (86.71%) were positive for Escherichia coli, 10 cases (6.99%) for Klebsiella pneumoniae, 7 cases (4.89%) for Proteus mirabilis, and 2 cases (1.40%) for Pseudomonas aeruginosa (Table 1).

Figure 1 Participant flow diagram showing the selection of the final study population. UTI, urinary tract infection; VCUG, voiding cystourethrography; VUR, vesicoureteral reflux.

The baseline characteristics of pediatric patients with and without acute kidney damage are summarized in Table 2. Based on the results of ^99mTc-DMSA scintigraphy, among the 143 children enrolled in the study, 101 were classified into the acute kidney damage group (characterized by decreased or absent radiotracer uptake in the renal cortex), while 42 were assigned to the normal group. Within the acute kidney damage group, 57 patients exhibited decreased radiotracer uptake (27 males, 30 females), and 44 showed severe radiotracer defects (22 males, 22 females), indicative of more prominent renal parenchymal damage. No significant differences in age, gender or delayed time were observed between the two groups (all P>0.05). However, patients with acute kidney damage had higher peak fever temperatures than those in the normal group (P<0.01). Laboratory Inflammatory markers revealed distinct differences. CRP, absolute neutrophil count, PCT, and WBC count were significantly elevated in the acute kindey damage group. In contrast, no significant difference in NEUT% was found between the two groups.

Univariate logistic regression analysis revealed that CRP (OR 1.019, 95% CI: 1.009–1.030; P<0.001), absolute neutrophil count (OR 1.078, 95% CI: 1.006–1.156; P=0.03), and PCT (OR 2.086, 95% CI: 1.289–3.374; P=0.003) were significantly associated with acute kidney damage in children with febrile UTIs, whereas delayed time and WBC count exhibited no predictive value (Table 3). Subsequently, multivariate binary logistic regression further identified CRP (OR 1.013, 95% CI: 1.003–1.024; P=0.01) and PCT (OR 1.671, 95% CI: 1.066–2.621; P=0.03) as independent predictors of acute kidney damage (Table 4).

ROC curves were plotted (Figure 2) and demonstrated that CRP predicted acute kidney damage with moderate accuracy (AUC =0.718), whereas PCT showed superior predictive performance (AUC =0.815). However, combining CRP and PCT did not improve predictive discrimination (Table 5). Using a cutoff value of 56.61 mg/L, CRP yielded a sensitivity of 70.3% and a specificity of 66.7% for predicting acute kidney damage. With an optimal cutoff value of 0.26 ng/mL, PCT achieved a sensitivity of 87.1% and a specificity of 69.0% (Table 5). Figure 3 illustrates two representative cases: one child with acute kidney damage who had PCT >0.26 ng/mL but CRP <56.61 mg/L, and one patient without acute kidney damage who presented with elevated CRP but PCT below the cutoff of 0.26 ng/mL. Post hoc power analysis for the primary diagnostic accuracy analysis (AUC of PCT) was performed using the Hanley-McNeil method. With a two-sided type I error of 0.05 and the observed AUC of 0.815 (based on 101 patients with acute kidney damage and 42 without), the achieved statistical power to detect a significant difference from an AUC of 0.5 exceeded 99.9%.

Figure 2 The receiver operating characteristic curves to predict kidney damage of initial febrile urinary tract infection children.

Figure 3 Cases with and without renal scars. (A) A girl of 2 years old, the CRP and PCT were detected with 100.93 mg/L and 0.19 ng/mL, respectively, and no obvious renal damage was observed in Tc-99m DMSA renal scintigraphy. (B) A boy of 9 months, the CRP and PCT were detected with 42.35 mg/L and 0.36 ng/mL, respectively; Tc-99m DMSA renal scintigraphy showed severe radioactive distribution defect in the upper left kidney and local radioactive distribution decrease in the right kidney. CRP, C-reactive protein; DMSA, dimercaptosuccinic acid; PCT, procalcitonin.

Discussion

In this consecutive cohort of 143 hospitalized children with febrile UTI, we found that acute kidney damage-detected by ^99mTc-DMSA scintigraphy within one week of admission—affected 70.6% of the study population. Among inflammatory biomarkers, PCT emerged as the strongest independent predictor of acute kidney damage, outperforming CRP in discriminative ability (AUC 0.815 vs. 0.718). At an optimal cutoff of 0.26 ng/mL, PCT identified 87.1% of acute kidney damage cases with a specificity of 69.0%. These findings suggest that early measurement of PCT, when integrated with clinical assessment, could serve as a reliable, non-invasive screening tool to stratify children at risk for acute kidney involvement, potentially guiding the timely use of ^99mTc-DMSA scintigraphy or more aggressive supportive care.

Febrile UTI is one of the most common severe bacterial infections in the pediatric population and poses a substantial threat to kidney health. The pathophysiological process of ferbile UTI involves direct bacterial invasion of the renal parenchyma, which triggers a robust inflammatory response. Repeated or inadequately controlled acute inflammatory insults lead to irreversible cumulative damage, manifesting as permanent renal scarring (8,17). A large-scale electronic population-based cohort study from Wales, including 159,201 children with a mean follow-up of 9.53 years, demonstrated that children who developed UTI by age 7 years had a significantly higher risk of renal scarring (1.24%; adjusted odds ratio 4.60, 95% CI: 3.33–6.35) (19). Moreover, growing evidence indicates that recurrent febrile UTIs can lead to serious complications beyond scarring, including hypertension, progressive CKD, and, in severe cases, end-stage renal failure (4,20). This underscores the critical importance of early identification of children at highest risk of kidney damage. In this context, our finding that PCT-a rapidly responding bacterial-specific biomarker-achieved an AUC of 0.815 for detecting acute kidney damage provides a clinically actionable tool to identify these high-risk patients before irreversible injury occurs (21).

Clinical practice for imaging evaluation of pediatric UTI remains heterogeneous, partly due to the inherent limitations of each modality. As the reference standard for identifying renal scarring, ^99mTc-DMSA scintigraphy offers excellent sensitivity and specificity for detecting cortical defects (4). However, its routine application is constrained by multiple practical barriers, including substantial economic costs, ionizing radiation exposure, and limited accessibility across clinical settings. A cost analysis among commercially insured children showed that the mean total out-of-pocket cost for ^99mTc-DMSA scintigraphy was US $591—the highest among four imaging modalities, substantially exceeding that of VCUG (US $464) and other alternative methods (22). A 2025 systematic review similarly noted that ^99mTc-DMSA scans carry the dual burdens of radiation exposure and high costs, limiting their suitability for routine screening (4). Most primary care facilities lack dedicated nuclear medicine instrumentation such as SPECT scanners or gamma cameras. Although ^99mTc-DMSA scans use low-dose radiation (approximately 0.58–0.68 mSv per study for children), the risk—though small—cannot be entirely dismissed, particularly in the pediatric population, as children are more radiosensitive than adults (23). In contrast, RBUS, the most widely available imaging tool, is currently recommended by the AAP as the initial imaging study for all infants with febrile UTI. Nevertheless, a recent systematic review (16) assessing the diagnostic accuracy of RBUS for detecting renal scars in children found wide variability in sensitivity (15.9% to 88.0%) and specificity (67.1% to 98.2%). Additionally, all 18 reviewed studies had methodological flaws, with substantial heterogeneity across studies, and no consensus was reached regarding the effectiveness of ultrasound compared to ^99mTc-DMSA in detecting renal scars. Consequently, conventional gray-scale ultrasound cannot be relied upon to definitively exclude renal parenchymal involvement.

These limitations, combined with the invasive nature of VCUG (and its associated radiation exposure and risk of catheter-related complications), highlight a pressing gap in pediatric UTI management: the absence of a simple, widely available, and non-invasive test to accurately identify children who truly require advanced imaging. CRP has been extensively studied as a predictor of renal involvement in pediatric UTI. A prospective study of children under 2 years of age with first-episode febrile UTI found that 53% had acute pyelonephritis (APN) confirmed by acute ^99mTc-DMSA scintigraphy, and CRP levels >100 mg/L were significantly more frequent in children who subsequently developed permanent renal scarring compared to those without scarring (17). A recent systematic review and meta-analysis, pooling data from 28 studies and 2,300 participants, reported that PCT has good overall diagnostic accuracy for detecting APN (AUC 0.861, I²=29.8%) (8). Consistent with these prior reports, both CRP (OR 1.013, 95% CI: 1.003–1.024) and PCT (OR 1.671, 95% CI: 1.066–2.621) emerged as independent predictors in our multivariate model. However, our head-to-head comparison of ROC curves demonstrated that PCT (AUC 0.815) outperformed CRP (AUC 0.718) in discriminating acute kidney damage. Of note, combining the two markers did not improve predictive discrimination, suggesting that CRP may not provide additional predictive value beyond PCT in this setting.

Our optimal PCT cutoff of 0.26 ng/mL was lower than the 1.0 ng/mL reported by Bressan et al. for predicting renal scarring (24). This discrepancy may be attributed to differences in outcome definition (acute ^99mTc-DMSA abnormalities vs. permanent scarring), patient age distribution, or timing of PCT measurement. The superior diagnostic performance of PCT over CRP in our study can be mechanistically explained. Unlike CRP-a relatively non-specific acute-phase reactant synthesized by the liver in response to diverse causes of tissue damage (including viral infections and autoimmune conditions), PCT is a 116-amino acid polypeptide that circulates at very low concentrations under physiological conditions. During bacterial infections, bacterial endotoxins and pro-inflammatory cytokines stimulate macrophages and parenchymal tissues to synthesize and release substantial amounts of PCT. Serum PCT levels rise rapidly (detectable within 3–4 hours, peaking within 6–24 hours) and increase in proportion to the severity of infection, while remaining essentially unchanged in viral infections or autoimmune disorders (25). Given that bacterial pathogens are the primary etiology of pediatric UTIs, this bacterial-specific response likely accounts for PCT’s superior performance in identifying renal parenchymal bacterial invasion in our cohort. Beyond its predictive value for acute kidney damage, PCT may also facilitate antibiotic stewardship in pediatric UTI. Although the impact of PCT-guided algorithms on antibiotic duration remains debated-the UK BATCH RCT found that adding a PCT-guided algorithm to usual care did not significantly shorten intravenous antibiotic duration-accumulating evidence suggests that integrating PCT into routine clinical evaluation can not only improve the identification of children with acute kidney damage but also help rationalize antibiotic therapy (26-28). This may reduce unnecessary antibiotic exposure and the associated risk of antimicrobial resistance, a critical consideration in pediatric clinical practice given the global burden of antibiotic resistance.

Strengths

This study has several strengths. First, all enrolled children underwent ^99mTc-DMSA scintigraphy within an early window (one week after admission), with scans independently interpreted by two experienced nuclear medicine physicians blinded to clinical data-ensuring consistent and objective assessment of renal parenchymal involvement. Second, we conducted a comprehensive head-to-head comparison of five readily available inflammatory biomarkers (CRP, PCT, WBC count, absolute neutrophil count, and neutrophil percentage), all of which are routinely measured in most clinical settings, including primary care facilities lacking advanced imaging equipment. This differs from prior studies limited to single-marker analyses or smaller biomarker panels. Third, we established an optimized, pediatric-adapted PCT cutoff value of
0.26 ng/mL (sensitivity 87.1%), which offers a clinically practical threshold that can be immediately implemented in hospital laboratories. This enables timely risk stratification of children at high risk of renal cortical damage without the need for specialized equipment or complex algorithms. Fourth, by focusing on readily accessible blood biomarkers-CRP and PCT-our strategy effectively overcomes the inherent drawbacks of conventional imaging examinations, including the invasiveness of VCUG, the limited diagnostic sensitivity of renal ultrasound, as well as the high cost, radiation exposure, and restricted accessibility of ^99mTc-DMSA scintigraphy. Because CRP and PCT are routinely measured even in primary medical institutions that lack advanced imaging equipment such as SPECT scanners or gamma cameras, our findings provide a convenient, low-cost, and widely feasible point-of-care predictive tool for the management of pediatric febrile UTI.

Limitations

Several limitations should be acknowledged. First, this was a single-center retrospective study with a relatively small sample size. Although post hoc power exceeded 99.9% for the primary analysis, post hoc power calculations are a deterministic function of the p-value and provide no information beyond the confidence interval; power analysis should play no role once the data have been collected (29). We therefore rely on the precision of effect estimates: the AUC (95% CI: 0.737–0.893) is narrow and entirely above 0.7, indicating a stable diagnostic performance estimate despite the modest sample size (30). In contrast, the 95% CI for the PCT OR (1.066–2.621) is wide, reflecting genuine imprecision due to limited sample size, and external validation in larger cohorts is needed. Second, although ^99mTc-DMSA scintigraphy is the reference standard for detecting acute renal parenchymal inflammation, it carries inherent risks of misclassification. The diagnostic sensitivity of DMSA is age-dependent, with significantly lower detection rates in children under 2 years of age; 88.1% of our cohort were younger than 24 months. False-negative findings are more frequent when DMSA is performed very early in the disease course before sufficient inflammatory changes have developed (31). Moreover, interobserver variability in DMSA interpretation remains a persistent challenge. In this study, all scans were acquired within 7 days of admission using a standardized protocol and interpreted independently by two experienced nuclear medicine physicians blinded to clinical data, with discrepancies resolved by consensus. Additionally, the kinetics of PCT and CRP depend critically on the timing of measurement relative to fever onset. Because precise timestamps of blood sampling relative to fever onset were not uniformly recorded in this retrospective dataset, we cannot fully adjust for this factor beyond the variable “delayed time” (hours from fever onset to admission). Consequently, the predictive performance of these biomarkers may be influenced by variation in sampling time. Future prospective studies with standardized serial sampling protocols should confirm whether the optimal PCT cutoff of 0.26 ng/mL remains robust across different fever durations. Nonetheless, these inherent limitations should be considered when interpreting our findings. Third, urine collection using bags in infants <24 months carries contamination risk; we used a standardized protocol to minimize this, but the risk remains. Fourth, our hospitalized cohort may not represent milder outpatient febrile UTIs, limiting extrapolation to milder outpatient populations. Fifth, RBUS and VCUG findings were not uniformly available and thus not included in the analysis. Although children with known urinary tract malformations or VUR were excluded, it remains possible that some included patients had undiagnosed low-grade VUR (grade I–II) that was not investigated because routine VCUG is not recommended after a first febrile UTI in the absence of abnormal RBUS findings (2011 AAP guideline). PCT has been shown to be independently associated with high-grade VUR in children with first UTI (8,32). To minimise this potential confounding, we excluded all VUR-confirmed cases, but residual confounding from undetected low-grade VUR cannot be entirely excluded. Moreover, the literature does not currently provide a validated method to distinguish APN-from VUR-driven PCT elevation based on a single admission measurement. Future prospective studies with systematic VCUG screening in all participants are needed to disentangle the independent contributions of renal parenchymal inflammation and underlying VUR to elevated PCT levels. Sixth, non-E. coli pathogens were too few (13.3%) for subgroup analysis. Finally, we lacked follow-up DMSA to distinguish acute reversible lesions from permanent scarring and long-term outcome data, which prevents assessment of PCT’s predictive value for chronic renal sequelae.

Given these limitations, our findings should be considered preliminary and warrant further investigation. Future large-scale, multicenter prospective studies are needed to include both inpatient and outpatient children, adopt standardized imaging protocols and long-term follow-up, and collect complete clinical and microbiological data. Such well-designed trials will facilitate reliable pathogen-stratified analyses and enable a more comprehensive assessment of biomarker performance in predicting short- and long-term renal outcomes after febrile UTI in children.

Conclusions

In conclusion, this study demonstrates that among routine inflammatory biomarkers, PCT outperforms CRP in predicting acute kidney damage in children with febrile UTI. The optimized cutoff value of 0.26 ng/mL provides a clinically practical threshold (sensitivity, 87.1%). When integrated with clinical assessment, early PCT measurement can serve as a reliable, non-invasive screening tool to stratify children at risk of acute kidney involvement, thereby potentially guiding the selective application of ^99mTc-DMSA scintigraphy and reducing unnecessary imaging, radiation exposure, and healthcare costs in low-risk children. Future large-scale, prospective multicenter studies with long-term follow-up are needed to validate these findings and further explore the role of PCT in monitoring therapeutic response and guiding antibiotic stewardship in pediatric UTI.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STARD reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0179/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0179/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0179/prf

Funding: This work was supported by Science and Technology Plan Project of Wenzhou Municipality (Nos. Y2023199 and Y20240470).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-1-0179/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Ethics Committee of The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University (No. 2024-K-339-01) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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