The prognostic value of the neutrophil‑to‑platelet ratio for predicting postoperative sepsis complications after ureteroscopic lithotripsy

Introduction

Sepsis is one of the most severe complications following ureteroscopic lithotripsy (URSL), characterized by a high clinical incidence (5–10%), rapid progression, and significant mortality rates (20–40%), making it a leading cause of perioperative death (1-3). The pathogenesis involves bacterial endotoxin release during lithotripsy, with entry into the bloodstream via surgical surfaces, potentially leading to systemic inflammatory response and organ dysfunction (4-6). According to the sepsis-3 criteria, diagnosis requires a confirmed infection source and an increase in the Sequential Organ Failure Assessment (SOFA) score ≥2 points (7,8). However, the SOFA score, while comprehensive, relies on markers of established organ dysfunction, often resulting in a diagnostic delay until patients are already critically ill (7,9,10). This delay underscores the critical unmet need for biomarkers capable of predicting sepsis in the asymptomatic window prior to the fulfillment of these formal criteria (1,6,11). Such a biomarker would enable pre-emptive therapeutic interventions, potentially altering the disease course and improving patient outcomes.

Previous studies have established that hematological changes, notably a significant rise in neutrophils and a fall in platelets, are established hallmarks of sepsis (12,13). We therefore hypothesized that the neutrophil-to-platelet ratio (NPR), integrating these two pathological axes, could serve as a novel composite biomarker for early prediction. While existing multivariable models [e.g., SOFA, quick SOFA (qSOFA)] are not tailored to URSL-specific risks (7-9), a rapidly accessible biomarker like NPR could bridge this gap. This study is the first to rigorously evaluate the predictive value of NPR, measured at the specific 3-hour postoperative time point, in an independent cohort of patients undergoing URSL. We aimed to validate NPR’s early predictive accuracy as a critical step towards developing enhanced risk-stratification models. We present this article in accordance with the TRIPOD reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-380/rc).

Methods

Study design and population

This study was registered at the Chinese Clinical Trial Registry (Registration number: ChiCTR2400092429). Clinical data from 674 patients undergoing URSL in the Department of Urology at Shanghai Tenth People’s Hospital (January 2024 to December 2024) were retrospectively collected. After screening based on inclusion/exclusion criteria, 385 patients were enrolled. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Shanghai Tenth People’s Hospital Ethics Committee (Project identification number: SHSY-IEC-5.0/24K100/P01). Informed consent was waived in this retrospective study.

Based on postoperative outcomes, patients were categorized into a sepsis group (n=40) and a control group (n=345). Laboratory data for all patients were collected at 3-hour postoperatively, prior to the manifestation of any clinical signs of sepsis. Subsequently, patients were monitored for the development of sepsis until 72 hours post-surgery. Patients who exhibited signs of sepsis before or at the 3-hour blood collection were excluded. Inclusion in the sepsis group was limited to those who developed sepsis strictly after the 3-hour time point.

Diagnosis required: (I) positive urine culture (≥10⁵ CFU/mL); (II) SOFA score increase ≥2 points from baseline; (III) meeting criteria within the 72-hour observation window.

Although urine culture results may not be available within 72 hours in routine practice, we used it as a definitive microbiological criterion to confirm urinary tract infection. In cases where culture results were pending beyond 72 hours, clinical progression and SOFA score were primarily used for initial assessment, but only patients with confirmed positive culture were included in the sepsis group to ensure specificity.

Rationale for postoperative sampling timepoint

The 3-hour postoperative blood sampling was a component of our institution’s standard clinical protocol for all patients undergoing URSL, ensuring the practicality and uniformity of data collection. The 3-hour postoperative time point was selected for blood sampling based on a critical pathophysiological window. It allows sufficient time for the initial surgical inflammatory response to manifest in the peripheral blood, yet precedes the typical clinical onset of sepsis, aligning with the study’s goal of prediction rather than diagnosis. This timing also minimizes the confounding influence of immediate anesthesia and fluid shifts, providing a more stable reflection of the patient’s homeostatic response.

Inclusion and exclusion criteria

Inclusion criteria:

• Patients undergoing initial URSL at our department between January 2024 and December 2024;
• Complete laboratory results with all tests performed at our hospital;
• Subsequent treatment, observation, and follow-up visits conducted at our hospital;
• No underlying systemic diseases.

Exclusion criteria:

• Incomplete laboratory data: excluded per pre-defined protocol for complete-case analysis to ensure data integrity for multivariate modeling.
• History of prior stone-related treatments before admission: excluded to eliminate confounding effects of previous interventions on surgical outcomes and inflammatory response.
• Patients with evidence of active or recent infection (within 4 weeks prior to surgery), including sepsis, at any time prior to or at the 3-hour postoperative blood draw.
  • Preoperative infection: defined as the presence of fever (body temperature >38.0 °C), positive urine culture (≥10⁵ CFU/mL), elevated white blood cell count (WBC) (>10×10⁹/L) with clinical signs of infection (e.g., chills, dysuria, flank pain), or any other diagnosed active infection at the time of hospital admission;
  • Perioperative sepsis: defined as meeting the sepsis-3 criteria (suspected infection + an increase in SOFA score ≥2 points) before or at the exact time of the 3-hour postoperative blood sampling.
• Severe underlying diseases or immunocompromised status: (e.g., advanced heart/liver/renal failure, active cancer chemotherapy, steroid use). Excluded as their altered immune and inflammatory responses could confound the interpretation of sepsis biomarkers (Figure 1).

Figure 1 Study flow diagram in the present study. ROC, receiver operating characteristic; SOFA, Sequential Organ Failure Assessment.

Clinical data collection

Laboratory data, including C-reactive protein (CRP), WBC, creatinine, platelet count, neutrophil count, lymphocyte count, and monocyte count, were collected from venous blood samples drawn 3-hour postoperatively (T0 defined as the end of surgery).

Ratios were calculated as:

• NPR = neutrophil count/platelet count;
• NLR (neutrophil-to-lymphocyte ratio) = neutrophil count/lymphocyte count;
• MLR (monocyte-to-lymphocyte ratio) = monocyte count/lymphocyte count;
• PLR (platelet-to-lymphocyte ratio) = platelet count/lymphocyte count.

All hematological parameters were measured using Sysmex XN-9000 automated analyzer (Sysmex Corporation, Japan) within 30 minutes of sample collection.

Complete-case analysis was employed for all statistical modeling. Handling of missing data: patients with any missing laboratory variables (n=29, 4.3% of screened cohort) were excluded per predefined criteria; no imputation methods were applied, as missingness was minimal (<5%) according to standard practice for low missingness rates.

Surgical and perioperative management

All patients underwent URSL utilizing a 200 µm holmium laser (Lumenis Pulse 120H) with energy settings ranging from 0.8 to 1.2 Joules and a frequency of 10 to 15 Hertz. Intraoperative irrigation pressure was strictly maintained below 40 cmH₂O using a gravity-fed irrigation system. Antibiotic prophylaxis followed institutional guidelines. For patients without a history of multidrug-resistant organisms or recent positive urine cultures, intravenous cefuroxime (1.5 g) was administered 30 minutes before the commencement of the URSL procedure, with an additional dose given if the procedure duration exceeded 3-hour. In the event of suspected sepsis, empirical intravenous piperacillin-tazobactam (4.5 g every 8 hours) was initiated. For patients with known resistance or prior infections, prophylaxis was tailored according to prior antimicrobial susceptibility testing results.

Statistical analysis

To mitigate assessment bias, the study implemented a blinding protocol: microbiologists processing cultures were blinded to NPR values, and SOFA score assessors were blinded to laboratory results. Statistical analyses were performed using SPSS 27.0. Continuous variables were expressed as mean ± standard deviation or median (interquartile range) based on distribution, and compared using Student’s t-test or Mann-Whitney U test. Categorical variables were compared using the Chi-squared or Fisher’s exact test.

To address potential multicollinearity among highly correlated hematological parameters (e.g., between NPR and its components), we employed a two-model multivariable logistic regression approach:

• Model A (Clinical Parameters Model) included: CRP, Plt, Neu, Lym, Mon, Cr, age, and gender.
• Model B (Inflammatory Ratios Model) included: NLR, MLR, PLR, and NPR.

Variables with a P value <0.05 in univariate analysis were entered into their respective models via backward stepwise selection. The diagnostic performance of significant predictors was evaluated using receiver operating characteristic (ROC) curve analysis, with the area under the curve (AUC) reported.

Results

Baseline characteristics

After applying the pre-defined inclusion and exclusion criteria, 385 patients were enrolled. All patients completed 72-hour postoperative monitoring with no loss to follow-up, of whom 40 (10.4%) developed sepsis (sepsis group) and 345 (89.6%) served as controls (control group). None of the patients included in the sepsis group exhibited signs of sepsis at the time of blood collection. All sepsis cases developed thereafter, within the 72-hour monitoring window.

Comparative analysis of baseline characteristics is detailed in Table 1. Briefly, the sepsis group was significantly older and had a higher proportion of female patients compared to the control group (P<0.001). As expected, the sepsis group presented with significantly elevated levels of inflammatory markers, including CRP, WBC, neutrophil count, monocyte count, NLR, NPR, and MLR (P<0.001), alongside significantly lower lymphocyte and platelet counts (P<0.001). No significant differences were observed in stone location (P=0.95), serum uric acid levels (P=0.70), or PLR (P=0.43) between the two groups (P>0.05).

Microbiological characteristics

Postoperative urine cultures were positive in all 40 patients in the sepsis group. The most frequently isolated pathogen was Escherichia coli (45.0%), followed by Enterococcus faecalis (27.5%) and Klebsiella pneumoniae (15.0%). Blood cultures were positive in 18 patients (45.0%), with a similar distribution of pathogens, predominantly E. coli (55.5% of positive cultures). The detailed results are presented in Table 2.

Independent risk factors

To identify independent predictors, variables significant in univariate analysis (P<0.05) were advanced to multivariable logistic regression. As pre-specified in the statistical analysis plan to mitigate multicollinearity, two separate models were constructed.

Model A (Clinical Parameters Model) confirmed female gender as an independent risk factor for sepsis (P=0.04). Although CRP and lymphocyte count showed strong trends, they did not reach statistical significance in the multivariate model (P=0.053 and P=0.054, respectively). The results of Model A are presented in Table 3.

Model B (Inflammatory Ratios Model) demonstrated that both NPR (P<0.001) and MLR (P=0.03) were powerful and independent predictors of postoperative sepsis. In contrast, NLR did not retain independent predictive value in this model. The results of Model B are summarized in Table 3.

Diagnostic performance of biomarkers

The diagnostic performance of the significant predictors was evaluated using ROC curve analysis (Figure 2). NPR demonstrated the highest diagnostic efficacy among all biomarkers, with an AUC of 0.896 (95% CI: 0.838–0.955). The optimal cutoff value for NPR was >2.77×10⁻², yielding a sensitivity of 80.0% and a specificity of 88.4%. For comparison, the AUC for CRP was 0.825 (95% CI: 0.744–0.906), while the AUC values for NLR, MLR, PLR and gender were 0.814, 0.774, 0.493 and 0.638, respectively. The comprehensive results of the ROC analysis are provided in Table 4.

Figure 2 ROC curve for NPR, NLR, MLR, PLR, CRP, gender. CRP, C-reactive protein; MLR, monocyte-to-lymphocyte ratio; NLR, neutrophil-to-lymphocyte ratio; NPR, neutrophil-to-platelet ratio; PLR, platelet-to-lymphocyte ratio; ROC, receiver operating characteristic.

Based on these findings, an NPR value exceeding 2.77×10⁻² at 3-hour postoperatively signifies a significantly increased risk of sepsis, underscoring its value as an early predictive biomarker.

To use NPR for individual sepsis risk prediction:

• Timing: obtain complete blood count (CBC) at 3-hour post-URSL.
• Calculation: NPR = [Neutrophil count (×10⁹/L)]/[Platelet count (×10⁹/L)].
  • NPR ≤2.77×10⁻² → Low risk (routine monitoring).
  • NPR >2.77×10⁻² → High risk (initiate sepsis protocol: blood culture, antibiotics, hemodynamic support).

A benchmark analysis comparing the prognostic value of NPR across various clinical contexts is provided in Table S1.

Discussion

Sepsis remains a severe complication following URSL, driven by a complex interplay of infection, dysregulated inflammation, and coagulopathy (14-16). This study demonstrates that the NPR, calculated from a routine CBC obtained just 3-hour postoperatively, serves as a powerful and independent early predictor of this complication. We identified NPR, MLR, and female gender as independent risk factors. Crucially, NPR emerged as the superior biomarker, achieving an AUC of 0.896, significantly outperforming MLR (AUC =0.774) and other established ratios, underscoring its paramount utility for early risk stratification. Although CRP showed notable discriminative ability (AUC =0.825), it was not retained as an independent predictor in the multivariate model (P=0.053). An NPR threshold of >2.77×10⁻² at 3-hour post-URSL provides a valuable early warning signal.

The superior predictive performance of NPR stems from its unique capacity to concurrently reflect the dual pathological pillars of early sepsis: hyperinflammation and emerging coagulopathy (17-19). The procedural release of endotoxins and bacteria during URSL triggers a rapid systemic inflammatory response, characterized by pronounced neutrophilia (20-22). Concurrently, the incipient cytokine storm can induce endothelial injury and microvascular thrombosis, initiating platelet consumption. The NPR elegantly captures this interplay—the rise in neutrophils and the beginning of a relative platelet decline—often before overt thrombocytopenia manifests due to compensatory mechanisms, thus providing a more sensitive composite signal than its individual components (23-27). The microbiological profile of our sepsis cohort, dominated by Gram-negative uropathogens such as Escherichia coli and Klebsiella pneumoniae, is consistent with the typical pathophysiology of urosepsis and reinforces that NPR elevation signifies a response to a systemic inflammatory cascade triggered by these common pathogens (28,29).

Despite its notable predictive capacity (AUC =0.825), the significant elevation of CRP at the 3-hour postoperative mark warrants specific discussion given its atypical early kinetics. This can be explained by a ‘two-hit’ model of hepatic priming. Patients with obstructive urolithiasis often experience a first hit of subclinical, chronic inflammation from bacterial colonization, pre-sensitizing hepatocytes. The surgical trauma of URSL then serves as a second hit, triggering an accelerated, explosive CRP synthesis response that bypasses the typical 4–6-hour lag phase (30-32). However, the predictive information of CRP, which reflects the magnitude of the inflammatory burden, may be subordinate to the more immediate pathophysiological interplay between hyperinflammation and coagulopathy directly reflected by NPR. The inclusion of MLR and female gender as independent risk factors further enriches the risk profile. An elevated MLR may signify increased monocyte activation coupled with relative lymphopenia, both of which are recognized features of the immune dysregulation characteristic of sepsis (33,34). The association with female gender, consistent with broader epidemiological trends in urinary tract infections, may be attributable to anatomical factors or sex-based differences in immune response, underscoring the importance of considering patient demographics in risk assessment (35,36). These findings suggest the potential for future multi-factorial models that combine NPR with these additional variables.

When considering the clinical implementation of our findings, it is essential to align them with the current trend towards outpatient URSL management. The utility of the 3-hour NPR is not to justify routine hospitalization for all patients, which would be neither cost-effective nor patient-centric, but to enable risk-adapted stratification. A paramount advantage of NPR is its seamless, zero-cost integration into the standard postoperative workflow. The 3-hour postoperative blood sampling was part of our institution’s routine clinical protocol for URSL patients, ensuring the practicality of this approach. Since NPR is derived from the differential white blood cell count and platelet count within a standard CBC, its calculation imposes no additional blood draw, no extra cost, and no delay in obtaining results. Therefore, we propose that NPR functions not as a replacement for clinical judgment or established markers, but as an early warning system within a selective monitoring strategy. In the evolving landscape of outpatient URSL, an elevated NPR (>2.77×10⁻²) in an otherwise asymptomatic patient at 3-hour should prompt intensified monitoring, lower the threshold for initiating blood cultures, and justify mandatory inpatient observation for high-risk individuals. Conversely, a low NPR value could provide objective reassurance to support the safe discharge of low-risk patients with standard precautions, thereby optimizing healthcare resource allocation and enhancing patient safety through pre-emptive intervention.

The diagnostic accuracy of NPR for post-URSL sepsis in our cohort (AUC =0.896) stands in stark contrast to its more modest performance across a spectrum of other conditions, as detailed in our benchmark analysis (Table S1). While NPR demonstrates utility in general sepsis (AUC =0.628) (37,38), acute myocardial infarction (AUC =0.755) (39), and even chronic conditions like osteoarthritis (AUC =0.62–0.69), its predictive power in our setting is unparalleled (40-43). This suggests that the violent hematological shift within 3 hours post-URSL is both quantitatively and qualitatively distinct. The clinical implication is profound: such a high AUC indicates that NPR possesses the discriminatory capacity to be a cornerstone for early warning systems in post-urological surgery care, potentially enabling interventions hours before fulminant sepsis develops.

Despite these promising findings, our study has limitations that must be acknowledged. Its retrospective, single-center design carries an inherent risk of selection bias and potential information bias. Moreover, our study design incorporates specific choices regarding infection diagnosis and patient selection that warrant consideration as limitations. Specifically, our diagnostic criterion for postoperative sepsis mandated a positive urine culture, which may not fully capture all cases of urosepsis occurring within the 72-hour follow-up period, potentially leading to an underestimation of the true sepsis rate. Similarly, the exclusion of patients with preoperative positive urine cultures or recent urinary tract infections, while methodologically necessary to isolate the postoperative event, limits the generalizability of our findings to these common and clinically important high-risk subgroups. Additionally, the absence of preoperative hematological baselines, while mitigated by strict exclusion criteria, precludes an analysis of dynamic changes (ΔNPR), which might have offered even greater predictive power. Furthermore, the exclusion of patients with significant comorbidities enhances internal validity but may limit the generalizability of our findings to a broader, more representative urolithiasis population. It should also be noted that detailed procedural metrics such as operative time were not analyzed, and their potential confounding influence cannot be excluded. Most critically, the reported diagnostic performance stems from the development cohort alone. External validation in prospective, multicenter cohorts is therefore an essential next step before widespread clinical implementation can be recommended. Future research should also focus on integrating NPR with clinical variables (including preoperative urine culture status) into multimodal predictive models and exploring the pathophysiological mechanisms of neutrophil-platelet interactions in sepsis pathogenesis. Furthermore, acknowledging that baseline adjustment would strengthen our findings, we have reframed our conclusion to highlight the absolute 3-hour NPR and will prospectively collect preoperative baselines in our planned validation cohort.

Conclusions

This study identified NPR as the most powerful independent predictor of sepsis following URSL, demonstrating superior diagnostic accuracy (AUC =0.89) at a critical 3-hour postoperative window. The predictive value of MLR and female gender further enriches the risk profile. Although not an independent predictor in the multivariate model, the considerable discriminative ability of CRP (AUC =0.82) should not be overlooked, suggesting its potential role as a valuable adjunctive marker alongside NPR.

The paramount clinical utility of NPR lies in its derivation from a routine postoperative CBC, offering a rapid, cost-free tool for early risk stratification. An elevated NPR (>2.77×10⁻²) in an asymptomatic patient warrants intensified monitoring and a lower threshold for pre-emptive intervention.

This study’s limitations, including its retrospective single-center design and the lack of preoperative hematological baselines, necessitate caution in generalizing the findings and highlight the potential for unmeasured confounding. Consequently, the imperative next step is the external validation of NPR in prospective, multicenter cohorts. Future research should prioritize the development of integrated models combining NPR with clinical variables and explore its precise pathophysiological role to refine perioperative management.

Acknowledgments

The authors sincerely appreciate the assistance of Jingyi Wu (University of Chinese Academy of Sciences) for his significant contribution to the analysis. The authors also appreciate the assistance of Wenyu Gu for review and editing. The authors sincerely appreciate the assistance of Heng Cao for his significant contribution.

Footnote

Reporting Checklist: The authors have completed the TRIPOD reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-380/rc

Data Sharing Statement: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-380/dss

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-380/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-380/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 Shanghai Tenth People’s Hospital Ethics Committee (Project identification number: SHSY-IEC-5.0/24K100/P01). Informed consent was waived in this retrospective study.

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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