Apelin levels in patients with polyuria-polydipsia syndrome upon copeptin stimulation tests

Differentiating between arginine vasopressin deficiency (AVP-D) and primary polydipsia (PP) requires a copeptin stimulation test. We aimed to characterize changes in apelin, an endogenous hormone antagonizing AVP, upon copeptin stimulation tests.

Post hoc secondary analysis of a multi-centric cross-over diagnostic study (NCT03572166).

Outpatients included at the University Hospital Basel.

Patients with AVP-D and PP.

Copeptin stimulation tests with hypertonic saline and arginine infusion.

The primary outcome was the absolute difference in apelin between baseline and peak of copeptin stimulation tests. Secondary objectives included the diagnostic ability of apelin.

Thirty-eight patients were analysed, 23 (60%) had PP and 15 (40%) had AVP-D. No difference was seen between baseline median (IQR) apelin levels in PP and AVP-D (1079 [912, 1225] and 910 [756, 1039] pmol/L, respectively). Upon hypertonic saline, apelin decreased by -241 (-326, -124) pmol/L in PP and -47.2 (-198, 5.86) pmol/L in AVP-D (P = .022). The area under the curve (AUC) to differentiate PP from AVP-D was 97.1% (95% CI, 90.5-100) for copeptin and 49.3% (95% CI, 30.4-68.1) for apelin (P < .001). Upon arginine, apelin decreased by -39.2 (-96.4, 39.8) pmol/L in PP and increased by 25.8 (2.8, 113.0) pmol/L in AVP-D (P = .1). The AUC was 97.1% (95% CI: 79.6-98.0) for copeptin and 60.5% (95% CI: 39.8-80.0) for apelin (P = .007).

Our findings suggest that apelin decreases to a greater extent in PP compared with AVP-D upon copeptin stimulation tests. However, copeptin remains the best marker to differentiate AVP-D from PP.