Urolithiasis, a common urological disorder with a global prevalence of approximately 10% (1), can lead to a series of clinical manifestations, including renal colic, hematuria, and urinary tract infections (UTIs). Currently, minimally invasive procedures are the primary treatment approach. With advancements in technology, the efficacy of minimally invasive surgery for urolithiasis has been widely recognized, demonstrating fewer complications and high stone clearance rates. However, as its application increases, the incidence of postoperative complications has also risen. Common complications include fever, hematuria, and infection, while more severe but rare complications encompass obstruction and urosepsis. Recent data have shown that postoperative UTI is influenced by multiple peri-operative factors, including operative time, stone burden and ureterorenoscope type (2). FUTI is one of the most frequent postoperative complications of urolithiasis. FUTI was defined as fever (>38 °C) accompanied by pyuria within one week postoperatively, after excluding other infectious etiologies. It may lead to severe conditions such as sepsis, septic shock, and even life-threatening outcomes (3, 4). Identifying risk factors is crucial for preventing infectious complications and mitigating associated risks. Although several studies have sought to identify risk factors for postoperative infectious complications in patients with urolithiasis, the evidence remains inconsistent (5–7). For instance, Cagdas Sene et al. (8) identified hydronephrosis, a history of UTIs, and elevated urinary white blood cell counts as significant independent predictors of FUTI, whereas Shigeki Koterazawa et al. (9) reported female sex, diabetes mellitus, and prolonged operative time as risk factors. Due to the variability and specificity among studies, systematic evidence regarding FUTI risk factors remains insufficient. This study employs a systematic review and meta-analysis to comprehensively evaluate the major factors influencing the occurrence of FUTI following minimally invasive surgery for urolithiasis. The findings aim to provide clinicians with valuable insights for risk stratification, personalized perioperative management, and targeted interventions to reduce the incidence of UTIs and improve patient outcomes.

This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (10). The study was registered on the PROSPERO platform (Registration No: CRD420251060966).

Urinary tract calculi are a common condition in urology. Minimally invasive surgery is a safe and effective treatment for urinary tract calculi. Although minimally invasive techniques achieve high stone-free rates with low morbidity, the overall complication rate ranges from 5% to 25%, with infections representing the most frequent complications (25). Postoperative FUTI is one of the most frequently considered significant complications and may even progress to sepsis. This study revealed that the overall prevalence of FUTI following urinary stone surgery was 17%, although this result exhibited substantial heterogeneity (I² > 97%). Such a degree of heterogeneity is not uncommon in this field and is consistent with previous research contexts (8, 26). The marked heterogeneity primarily stems from considerable variations across clinical centers in terms of patient demographic characteristics, surgical techniques, perioperative management, and most critically, the diagnostic criteria for FUTI—such as the fever threshold (>38 °C vs. >38.5 °C), the requirement for confirmatory urine culture results, and the time window for symptom onset (within 24 h vs. within 1 week postoperatively). The lack of standardization in these diagnostic criteria undoubtedly influences the pooled estimate, representing a key aspect that requires standardization in future research in this field. Sensitivity analysis conducted in this study confirmed the robustness of the pooled results, thereby enhancing the credibility of the main findings.

Sensitivity analysis (Table 4) was crucial for evaluating the reliability of the study findings. The analysis revealed that factors including diabetes, renal insufficiency, preoperative pyuria, preoperative bacteriuria, perinephric fat stranding, tissue rim sign, and stone size exhibited consistent results between the fixed-effect and random-effect models, indicating that these associations were robust and reliable. In contrast, the pooled results for factors such as stone location, preoperative hydronephrosis, preoperative procalcitonin, operative time, urinary white blood cell count, and gender demonstrated significant alterations between different models, suggesting that the reliability of these findings is limited and that caution should be exercised in their clinical interpretation.

The systematically extracted study characteristics (Supplementary Tables 4, 5) provide crucial context for interpreting the considerable heterogeneity observed in this meta-analysis. Notable variability existed in perioperative antibiotic protocols. Only one study (Group A) detailed a guideline-adherent approach involving routine preoperative urine culture with targeted antibiotic therapy. The qualitative comparison suggested a lower FUTI incidence in this study compared to the median incidence among studies with less clearly defined protocols (Group B), highlighting the potentially modifiable role of standardized antibiotic prophylaxis in infection-related outcomes. Although the included studies primarily involved ureteroscopic lithotripsy (URS) or retrograde intrarenal surgery (RIRS) for ureteral or renal stones, meaningful subgroup analysis by surgical technique was precluded due to frequent lack of specific technical parameters. This reporting inconsistency itself constitutes a key finding and underscores that these methodological and clinical variables are likely major contributors to unexplained heterogeneity.

The results of this study indicate that diabetes is a strong predictor of FUTI (OR = 2.18). The underlying mechanisms involve impaired immune function due to hyperglycemia—such as suppressed T-cell response and decreased complement activity—microcirculatory disturbances, and an environment conducive to bacterial proliferation. The European Association of Urology (EAU) guidelines also emphasize the importance of enhanced perioperative glycemic control and infection prevention in diabetic patients (27). Renal insufficiency (OR = 3.19) represents another robust predictive factor, the pathological mechanism of which may be associated with decreased tubular clearance leading to prolonged retention of calculi and pathogens, thereby facilitating the formation of biofilm-related infections (18). Therefore, preoperative assessment and optimization of renal function are crucial.

Preoperative bacteriuria (OR = 2.45) was identified as a key modifiable risk factor. Kutchukian et al. (28) demonstrated that a positive urine culture is an independent correlate of postoperative febrile infections. These findings support the practice of performing preoperative urine cultures and administering targeted antibiotic therapy, which aligns with the EAU guidelines recommending the management of asymptomatic bacteriuria before surgery to reduce postoperative infection risk (27, 29). Similarly, preoperative pyuria (OR = 4.05) was also significantly associated with an increased incidence of postoperative FUTI. Although the definition threshold (e.g., ≥5 WBC/HPF vs. ≥10 WBC/HPF) (30) remains controversial across studies (13, 18, 29), its value as a marker of infection and inflammation is well established.

Perirenal space alterations result from fluid release within the bridging septa of perirenal fat, caused by increased lymphatic pressure, inflammation, and edema in the ureteral wall surrounding a renal calculus. The perirenal fat stranding sign is observed in 36%–82% of adult patients with ureteral stones (14). The tissue rim sign arises as a consequence of inflammatory and edematous changes in the ureteral wall, induced by contact with an obstructing ureteral stone; its presence often indicates ureteral wall inflammation and edema (22). According to a study by Jin Woo Kim et al. (14), the tissue rim sign has been reported in 34%–76% of ureteral stone cases and serves as a useful indicator for distinguishing ureteral stones from phleboliths. Therefore, both the perirenal fat stranding and tissue rim signs on non-contrast helical computed tomography reflect inflammatory changes secondary to urinary tract obstruction by calculi. These CT signs provide an objective basis for non-invasive preoperative risk assessment.

Although operative time (OR = 1.05) and stone size (OR = 1.29) emerged as significant factors in the primary analysis, their high heterogeneity (I² > 90%) and instability during model transformation suggest that their effects may be moderated by various factors such as surgical technique, stone composition, and irrigation pressure (12, 24). Therefore, they should be regarded as potential risk indicators rather than independent strong determinants for decision-making. Although preoperative procalcitonin (PCT) was statistically significant (OR = 1.08, P = 0.003), its odds ratio was close to 1.0, indicating a limited absolute effect size and clinical predictive value. Therefore, PCT may be more suitable as a reference indicator in comprehensive assessments rather than serving as an independent decision-making basis.

Based on the robust predictors identified in this study, we propose a targeted perioperative management framework for risk stratification and outcome optimization. First, for patients with diabetes mellitus, strict perioperative blood glucose monitoring and management should be implemented. Urologists should collaborate closely with endocrinologists or primary care physicians to achieve optimal glycemic control (e.g., preoperative HbA1c < 7% as recommended by EAU guidelines) before elective surgery, in order to improve immune function and reduce the risk of infection (27). Such multidisciplinary preoperative optimization is crucial for reducing infection risk in these high-risk patients. Second, for patients with preoperative bacteriuria or pyuria, targeted antibiotic therapy based on preoperative urine culture and sensitivity results is strongly recommended, rather than relying solely on empirical treatment. Even asymptomatic bacteriuria should be considered for eradication prior to surgery, in accordance with EAU guidelines on infection prevention (27). Third, operative time (OR = 1.05), as a modifiable surgical factor, warrants particular attention. Although stone size and complexity partially determine the required operative duration, our findings support the implementation of stricter time-consciousness in surgical planning and quality control. The surgical team should be aware that the risk of FUTI increases continuously with prolonged operative time, particularly beyond 75 min (12). This underscores the importance of optimizing surgical efficiency and workflow through adequate preoperative planning (e.g., detailed imaging review), the use of modern high-energy devices and lasers, and consideration of staged procedures or suitable alternatives (such as PCNL) for particularly complex or large stones. Proactive management of operative time is a key component in achieving high-quality surgical outcomes. Fourth, in patients with imaging findings such as perinephric fat stranding or tissue rim sign on CT, which indicate more severe local inflammation and obstruction, surgeons should adjust their surgical strategy accordingly. For instance, anticipating increased surgical difficulty, an experienced surgeon should be assigned, and efforts should be made to minimize operative time and reduce irrigation pressure and duration. Finally, a risk stratification model should be established: a simple preoperative risk assessment tool based on the robust potential factors derived from this meta-analysis (e.g., diabetes, renal insufficiency, bacteriuria, CT findings) could be developed in the future to identify high-risk patients and implement more aggressive preventive measures, such as extended prophylactic antibiotic use or intensified postoperative monitoring.

This study has several limitations: (1) The inclusion was restricted to Chinese and English publications, potentially introducing language bias; (2) Some included single-center studies from China may exhibit temporal and geographical overlaps, raising the risk of duplicate inclusion of the same patient population in the pooled analysis; (3) All included literature originated from published studies, which may be subject to selective publication bias (e.g., unpublished negative results); (4) A relatively high proportion of the included studies employed retrospective case-control designs, and the number of studies available for the analysis of each risk factor was limited, which may affect the robustness of our findings and hinder definitive causal inferences; (5) There was substantial unexplained heterogeneity among the included studies, strongly suggesting the presence of numerous study-level or patient-level confounding factors beyond the macro-level factor of language or region. Although we extracted detailed data on antibiotic management and surgical characteristics, the reporting of these parameters was highly inconsistent and often incomplete across studies (Supplementary Tables 4, 5). This precluded meaningful subgroup or sensitivity analyses based on surgical technique or specific antibiotic protocols, which are important potential sources of the substantial unexplained heterogeneity. Furthermore, the definitions of FUTI varied considerably among studies (Supplementary Table 5), which is a major contributor to heterogeneity and a key area for standardization in future research.

Based on the above analysis, the synthesis of diabetes mellitus, renal insufficiency, preoperative hydronephrosis, elevated preoperative procalcitonin levels, preoperative pyuria, preoperative bacteriuria, perinephric fat stranding, tissue margin sign, operative duration, and stone size constitutes potential independent predictors for FUTI following surgery in patients with urinary calculi. These factors provide an evidence base for developing a preoperative risk stratification model. Future studies should focus on developing and validating clinical tools to identify high-risk patients and guide individualized perioperative management.