Salt Use Before Copeptin Testing
Patients should avoid salt intake before copeptin testing, as salt loading increases plasma osmolality and copeptin levels, which would interfere with accurate diagnostic interpretation of polyuria-polydipsia syndrome.
Why Salt Matters for Copeptin Testing
Copeptin is released in response to osmotic stimuli, and salt intake directly raises serum osmolality, which in turn stimulates copeptin secretion 1, 2. When evaluating patients for diabetes insipidus or primary polydipsia, the goal is to measure baseline or appropriately stimulated copeptin levels under controlled conditions—not levels artificially elevated by dietary salt 3, 4.
- Salt increases osmolality acutely: A 3g salt load can increase plasma osmolality by 6 mOsm/L within 2 hours, which is sufficient to stimulate copeptin release 5
- Copeptin responds rapidly to osmotic changes: The peptide exhibits a rapid response comparable to arginine vasopressin when plasma osmolality rises 1
- Small fluid changes affect copeptin: Even small amounts of oral fluid intake can significantly decrease copeptin levels, demonstrating how sensitive the marker is to osmotic shifts 1
Specific Testing Protocols
For Baseline Copeptin Measurement
When measuring baseline copeptin to differentiate nephrogenic diabetes insipidus from other causes, patients should present in their usual state without deliberate salt loading 6. A baseline copeptin >21.4 pmol/L identifies nephrogenic diabetes insipidus with 100% sensitivity and specificity, but this threshold assumes normal dietary conditions—not salt-loaded states 3, 4.
For Stimulated Copeptin Testing
When performing hypertonic saline infusion tests (the gold standard for differentiating central diabetes insipidus from primary polydipsia), the osmotic stimulus must be controlled and standardized 3:
- The test protocol itself uses hypertonic saline infusion to raise plasma sodium to ≥150 mmol/L in a controlled manner 6
- Pre-test salt loading would confound results by pre-elevating osmolality and copeptin before the standardized stimulus is applied 3
- A stimulated copeptin >4.9 pmol/L (after controlled saline infusion) differentiates primary polydipsia from partial central diabetes insipidus with 94-96% accuracy 3, 4
Practical Patient Instructions
Patients should:
- Maintain their usual diet without deliberate salt restriction or loading 6
- Avoid high-salt meals or snacks on the day of testing 5
- Have ad libitum access to fluids before testing to prevent dehydration 6
- Present in a normally hydrated state without forced water loading 1, 2
Critical Pitfall to Avoid
The most important error would be allowing patients to consume high-salt foods or supplements before testing, as this creates an uncontrolled osmotic stimulus that elevates copeptin independently of the underlying disorder being investigated 5. This would render baseline measurements uninterpretable and interfere with the standardized osmotic challenge used in diagnostic protocols 3, 4.
For patients with conditions like ADPKD where low-osmolar diets (including low sodium) have been studied to decrease copeptin levels, the principle remains: dietary sodium directly influences copeptin through osmotic mechanisms 6. Therefore, standardized conditions without salt loading are essential for accurate diagnostic testing.