Multimodal neuroimmune diagnostic profiling for pediatric lower urinary tract dysfunction associated with occult...

Persistent pediatric lower urinary tract dysfunction (LUTD) may be associated with occult sacral neural impairment, a clinically challenging condition characterized by subtle sacral pathway dysfunction without overt spinal dysraphism.

To develop, internally validate, and externally validate a multimodal diagnostic model integrating ultrasound, urodynamics, neuroelectrophysiology, and urinary biomarkers.

The development dataset comprised 120 records (45 occult sacral neuropathy-related LUTD, 45 functional non-neurogenic LUTD, and 30 controls). The target-condition label followed a prespecified multidisciplinary composite reference standard based on clinical phenotype, neurological examination, spinal/pelvic MRI when available, conventional urodynamic interpretation, and longitudinal course; biomarker values and model probabilities were not components of that label. Preanalytical metadata included pre-catheterization collection, centrifugation at 3000 or 5000 x g for 10 minutes, 1.0- 1.5 mL aliquots, storage at -80 °C, limited freeze-thaw exposure, and creatinine normalization. We internally validated a six-predictor logistic model with 1,000 bootstrap repetitions. We assessed a separate 90-record, two-site dataset without refitting or threshold optimization.

The locked model had an apparent AUC of 0.937 and Brier score of 0.099; optimism-corrected values were 0.920 and 0.116, respectively. The bootstrap mean calibration intercept was -0.065, and the slope was 1.032. In the external transportability analysis, the AUC was 0.928 (95% CI, 0.861-0.977), the Brier score was 0.098, the calibration intercept was -0.400, the calibration slope was 0.887, sensitivity was 80.0%, and specificity was 88.3%.

Multimodal neuroimmune profiling demonstrated strong discrimination and acceptable calibration after optimism correction and external validation in an independent two-site cohort. Prospective multicenter validation is required before clinical implementation.