Multimodal neuroimmune diagnostic profiling for pediatric lower urinary tract dysfunction associated with occult sacral nerve abnormalities

Background 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. Objective To develop, internally validate, and externally validate a multimodal diagnostic model integrating ultrasound, urodynamics, neuroelectrophysiology, and urinary biomarkers. Methods 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. Results 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%. Conclusion 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.