Urea-stimulated copeptin: a novel diagnostic approach in polyuria polydipsia syndrome.

Summary

An oral urea challenge robustly increases copeptin in healthy adults and those with primary polydipsia but not in AVP deficiency. A 120-minute copeptin cut-off of 3.5 pmol/L yielded 93% sensitivity and specificity, establishing the first simple oral copeptin-based test to differentiate AVP deficiency from primary polydipsia.

Key Findings

• In healthy adults, oral urea increased copeptin from 4.6 to 10.1 pmol/L at 120 minutes, while placebo showed no change (P < .001).
• In AVP deficiency, copeptin remained below detection throughout; in primary polydipsia, copeptin peaked at 150 minutes (~7.4 pmol/L).
• A 120-minute copeptin cut-off of 3.5 pmol/L provided 93% sensitivity and 93% specificity in differentiating AVP deficiency from primary polydipsia.

Clinical Implications

Clinicians could adopt an oral urea copeptin test to triage suspected diabetes insipidus vs primary polydipsia in outpatient settings, reducing need for specialized hypertonic saline testing; external validation and safety protocols are required.

Limitations

• Small sample sizes in both healthy volunteers and patient cohorts
• Open-label design in the patient pilot without external validation

Future Directions

Multicenter validation with standardized protocols, assessment in partial AVP deficiency and nephrogenic DI, and evaluation of safety/tolerability across comorbidities.