Comparative Diagnostic Performance of Copeptin After Hypertonic Saline Infusion Versus Water Deprivation Test in Pediatric Patients with Polyuria–Polydipsia Syndrome

Differentiating central diabetes insipidus (CDI), nephrogenic diabetes insipidus (NDI), and primary polydipsia (PP) in pediatric patients with polyuria-polydipsia syndrome (PPS) remains a clinical challenge. The water deprivation test (WDT) is the traditional gold standard; however, it is time-consuming, burdensome, and prone to equivocal results. Stimulated copeptin, a surrogate marker of vasopressin, has emerged as a promising diagnostic alternative. We conducted a prospective, observational, cross-sectional study involving 27 pediatric patients (ages 2-17) presenting with PPS. Each patient underwent a WDT with desmopressin and hypertonic saline infusion (3% NaCl) for stimulated copeptin testing. Diagnostic accuracy was assessed using clinical diagnoses as a reference. The WDT showed high accuracy with an area under the curve (AUC) of 0.97, and there was an increased optimal threshold of ≥14% urine osmolality after desmopressin acetate (1-deamino-8-D-arginine vasopressin, DDAVP) administration (sensitivity 88.9%, specificity 100%). Stimulated copeptin at a threshold of <6.5 pmol/L demonstrated 100% sensitivity and specificity (AUC = 1.00) for CDI versus PP. Basal copeptin ≥21.4 pmol/L accurately identified all NDI cases. The agreement between the WDT and copeptin was low (κ = 0.06, McNemar <i>p</i> = 0.021), suggesting that copeptin has greater specificity, particularly for borderline or partial CDI. These results support the use of stimulated copeptin as a first-line diagnostic tool in pediatric PPS, offering improved objectivity, tolerability, and diagnostic clarity compared with the WDT. Basal copeptin also demonstrated excellent performance in rapid noninvasive NDI identification.