Identifying urosepsis risk in diabetic patients with renal and ureteral calculi: Key predictors and clinical implications

Abstract

In their retrospective study of 298 diabetic patients with renal/ureteral calculi, Zhou et al identified critical predictors for urosepsis using multivariate logistic regression. Key findings revealed female gender (OR = 2.237, P = 0.03), advanced age (OR = 1.05/year, P = 0.002), fever (OR = 2.999, P = 0.015), severe hydronephrosis (OR = 6.129, P = 0.011), and elevated urinary markers-particularly urine leukocytes (U-LEU+++: OR = 66.0, P < 0.001) and glucose (U-GLU+++: OR = 7.248, P = 0.005) as independent risk factors. These readily accessible clinical parameters offer significant potential for early risk stratification in high-risk populations. While this STROBE-adherent study provides actionable insights, limitations include its single-center design and unaddressed antibiotic protocols. Future multicenter validation should assess residual stone impacts and optimize intervention thresholds. This work establishes a foundation for targeted surveillance protocols in diabetic urolithiasis management.

Key Words: Urosepsis; Diabetes mellitus; Renal calculi; Hydronephrosis; Urine leukocytes

Core Tip: This letter synthesizes pivotal insights from Zhou et al's landmark investigation (n = 298) examining urosepsis predictors in diabetic urolithiasis. Crucially, bedside-accessible metrics-severe hydronephrosis (OR = 6.129), pyuria (U-LEU+++: OR = 66.0), and glycosuria (U-GLU+++: OR = 7.248)-demonstrably outstrip demographic factors in risk stratification efficacy. Our analysis underscores the necessity for urinalysis-guided triage protocols in acute care settings, while advocating multicenter validation of residual stone burden implications and antimicrobial strategies. Collectively, this work establishes a low-resource surveillance framework applicable to global diabetic populations.

TO THE EDITOR

We read with interest Zhou et al's retrospective study examining risk factors for urosepsis in diabetic patients with renal or ureteral calculi[1]. Their rigorous analysis of 298 diabetes mellitus patients with renal/ureteral calculi identified critical predictors for urosepsis-a life-threatening complication associated with substantial mortality in high-risk populations[2]. By highlighting readily accessible markers for early intervention, their work addresses an urgent clinical need. We commend the investigators' comprehensive methodology and seek to contextualize these findings while proposing strategies to enhance their translational impact.

Study overview and discussion

Zhou et al's analysis delivers clinically actionable insights for urosepsis risk stratification in this population[1]. Their identification of key predictors-female sex (aOR = 2.237, P = 0.03), advanced age (OR = 1.05/year, P = 0.002), fever (OR = 3.00, P = 0.015), severe hydronephrosis (OR = 6.129, P = 0.011), and critical urinalysis markers including elevated urine leukocytes (U-LEU+++: OR = 66.0, P < 0.001) and urine glucose (U-GLU+++: OR = 7.248, P = 0.005)-aligns with established pathophysiology[3,4]. Urinary obstruction potentiates bacterial colonization, while diabetes-mediated immune dysfunction amplifies infectious sequelae[5]. The exceptional risk conferred by severe pyuria (U-LEU+++) underscores its role as a biomarker of uncontrolled inflammation, consistent with Chen et al's findings on IL-17A–driven urinary tract inflammation in urolithiasis via gut dysbiosis[6].

Three nuanced observations warrant particular attention: (1) The dose-dependent escalation of risk with U-GLU severity (OR: 4.617 for ++ → 7.248 for +++) highlights hyperglycemia’s dual pathology-impairing neutrophil function while fueling bacterial proliferation; (2) The threshold effect of hydronephrosis, where only severe obstruction predicted sepsis (OR = 6.129); and (3) The paradoxical inverse association between flank pain and urosepsis (OR = 0.51, P = 0.078), potentially reflecting neuropathic symptom masking in diabetics[7]. Clinically, these parameters enable resource-efficient triage. As rapid, low-cost assays feasible in primary care, U-LEU and U-GLU demonstrate superior predictive value over isolated imaging findings (e.g., hydronephrosis OR = 6.129 vs U-LEU OR = 66.0), advocating for urinalysis-driven escalation protocols.

Strengths and clinical relevance

The study exemplifies methodologically rigorous observational research, complying with STROBE guidelines and employing Firth’s penalized logistic regression to address small-sample bias. Severe hydronephrosis (OR = 6.129) and marked leukocyturia (U-LEU+++; OR = 66.0) emerged as paramount predictors, congruent with pathophysiology wherein obstruction facilitates bacterial colonization and leukocyturia signifies dysregulated immunity[8]. The inclusion of U-GLU (OR = 7.248 for +++) underscores diabetes-specific vulnerability, where hyperglycemia compromises neutrophil function and glycosuria provides substrate for bacterial growth[9-11]. These insights allow clinicians to prioritize high-risk patients (e.g., febrile elderly women with abnormal urinalysis) for intensive monitoring, potentially reducing sepsis-related mortality.

Limitations and future directions

Nevertheless, limitations constrain immediate generalization. The single-center retrospective design inherently limits generalizability, compounded by demographic imbalances wherein controls exhibited male predominance (53% vs 31.3% in urosepsis cases). This imbalance may have attenuated the observed effect size of female sex (aOR = 2.237) through selection bias[12]. Single-center investigations cannot account for regional variations in pathogen epidemiology, stone composition, management protocols, or demographics. Retrospective methodology risks unmeasured confounding, omitting critical factors like comprehensive glycemic metrics beyond HbA1c and detailed antibiotic histories. Importantly, the designation 'severe hydronephrosis' lacked explicit grading criteria. Clinical implementation requires standardized systems like the Society of Fetal Urology classification[13], as subjective assessments undermine risk stratification reliability. The absence of antibiotic data obscures prophylaxis impacts, while unaddressed residual stone burden-a known sepsis trigger[14]-precludes evidence-based surveillance protocols. These gaps impede clinical algorithm development.

Future investigations should prioritize three objectives: Validating predictors in multiethnic cohorts using standardized sepsis criteria (e.g., Sepsis-3); quantifying residual stones’ impact on urosepsis recurrence through longitudinal studies; and establishing evidence-based intervention thresholds to determine when severe hydronephrosis or U-LEU (+++) necessitates immediate decompression. We advocate for prospective multicenter designs incorporating predefined protocols for antibiotic utilization and residual stone assessment via computed tomography within 48 hours postoperatively. Machine learning models could enhance predictive accuracy by leveraging diverse datasets. Crucially, unresolved questions regarding targeted prophylaxis efficacy demand analysis of antibiotic interventions.

Conclusion

In conclusion, Zhou et al[1] establish a pragmatic framework for stratifying urosepsis risk in diabetic urolithiasis. Their identification of readily measurable predictors-U-LEU, U-GLU, and severe hydronephrosis-enables resource-efficient triage where advanced diagnostics are limited. Future research integrating antibiotic stewardship protocols, residual stone quantification, and evidence-based intervention thresholds will transform these insights into optimized clinical algorithms.