Copeptin Measurement After Mannitol and Hypertonic Saline for the Diagnosis of Polyuria-polydipsia Syndrome

Copeptin Measurement After Mannitol and Hypertonic Saline for the Diagnosis of Polyuria-polydipsia Syndrome

The aim of this study is to evaluate whether a new test using mannitol infusion can diagnose the cause of polyuria-polydipsia syndrome as accurately as the current standard test (hypertonic saline infusion) and to compare which test patients prefer. The goal is to identify a simpler and more patient-friendly diagnostic approach.

Polyuria-polydipsia syndrome (PPS), characterized by excessive urination and fluid intake, can have different underlying causes, including a deficiency of the hormone vasopressin (AVP-D) or excessive fluid intake without AVP-D (primary polydipsia). Correctly identifying the cause is essential, as the treatments differ and an incorrect diagnosis can negatively impact patient care.

A blood marker called copeptin is used to support the diagnosis, as it reflects vasopressin levels in the body. Currently, the most accurate method involves measuring copeptin after stimulation with hypertonic saline. However, this test is complex, requires close medical monitoring, and can be uncomfortable for patients.

Mannitol is a substance already used in routine clinical care and may offer a simpler way to stimulate copeptin release. Early results suggest that it could provide similar diagnostic accuracy with fewer side effects and better patient comfort.

This study is a randomized, cross-over, multicenter trial in which participants undergo both tests (mannitol and hypertonic saline) in random order. The study compares the diagnostic accuracy and patient preference for both methods, as well as safety and tolerability. In addition, it explores whether other clinical and laboratory measures can further improve the diagnosis of PPS.

Inclusion Criteria:

1. Age ≥ 18 years
2. Hypotonic polyuria/polydipsia syndrome defined as polyuria >40ml/kg body weight/24h and polydipsia >3l/24h; and urine osmolality <800mOsm/L or known AVP-D based on accepted criteria

Exclusion Criteria:

1. Polyuria/polydipsia secondary to diabetes mellitus, hypercalcemia, or hypokalemia
2. Diagnosis of AVP-R (Copeptin > 21.4 pmol/L)
3. Evidence of acute illness
4. Epilepsy requiring treatment
5. Uncontrolled arterial hypertension (blood pressure >160/100mmHg at baseline
6. eGFR < 60 ml/min/1,73 m2
7. Cardiac failure (NYHA III-IV)
8. Diagnosis of liver cirrhosis, Child-Pugh Class C
9. Uncorrected adrenal or thyroidal deficiency
10. Pregnancy or breastfeeding
11. Current or unresolved urinary obstruction
12. Enrollment in a clinical trial within the last 30 days
13. Patients refusing or unable to give written informed consent
14. Inability to follow study procedures