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

Objective: 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.

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

Setting: Outpatients included at the University Hospital Basel.

Participants: Patients with AVP-D and PP.

Interventions: Copeptin stimulation tests with hypertonic saline and arginine infusion.

Outcomes And Measures: 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.

Results: 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).

Conclusions And Relevance: 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.