Letter: Sex-Specific Urosepsis Prediction after Obstructive Ureteral Stones: SOFA Scoring Artifacts and Clinical Threshold Pitfalls

To the Editor,

We read with great interest the retrospective study by Basadonna et al. ¹ evaluating predictors of sepsis after urinary decompression for obstructive uropathy. While titled “gender-based,” the findings likely reflect biological “sex” differences. The central finding—that women face higher sepsis risk despite smaller stones and lower inflammatory markers—is compelling, aligning with previous evidence ² and European Association of Urology guidelines. ³ However, we must consider whether women truly possess a higher biological risk or if scoring artifacts play a role.

Women generally possess lower baseline serum creatinine; thus, identical absolute modest increases might disproportionately trigger a ≥2-point acute Sequential Organ Failure Assessment (SOFA) score increase. While these elevations reflect real acute kidney injury, a component-level SOFA analysis would clarify whether renal criterion disproportionately drove the observed sex differences. This phenomenon could partially account for an over-ascertainment of sepsis in women compared to men with similar illness severity.

A second issue concerns endpoint purity. Sepsis was defined by SOFA increases plus positive cultures. Crucially, bladder urine was sampled in all patients, whereas blood was cultured only upon fever or chills. As Mariappan and Loong demonstrated, midstream bladder cultures poorly predict infected urine proximal to an obstructing stone. ⁴ Without standardizing blood cultures or sampling renal pelvic urine during decompression, differential lower-tract colonization could bias case ascertainment, blurring the line between decompression-related transient bacteremia and true sepsis progression.

Statistically, the signal demands restraint before adoption as a clinical triage rule. The overall cohort had 64 sepsis events, but the male subgroup contained only 20. Multivariable modeling with so few events risks model instability and potential overfitting. ⁵ Furthermore, while deriving sex-specific cutoffs (e.g., C-reactive protein 6.2 mg/dL in women vs 7.1 mg/dL in men) is statistically feasible, a 0.9 mg/dL difference lacks practical bedside utility. Without bootstrap optimism correction, calibration plots, or decision-curve analysis, these thresholds should be treated as hypothesis-generating.

Future prospective studies should incorporate computed tomography-derived stone volume, record antibiotic timing as a time-dependent confounder, and utilize standardized pelvic cultures. Consideration of sex-adjusted SOFA thresholds or relative creatinine changes may help mitigate potential ascertainment bias. Despite these methodological limitations, Basadonna et al. have identified an important clinical signal worthy of further investigation, laying the necessary groundwork for sex-aware, calibrated emergency algorithms.