MON-042 Intravenous [pyr1]apelin-13 Increases Sodium Levels In Healthy Volunteers With Artificially Induced Syndrome Of Inappropriate Antidiuresis

Abstract Disclosure: S. Lustenberger: None. S. Monnerat: None. C.A. Bizzozero: None. F.A. Chapman: None. J. Santos de Jesus: None. E. Kustos-Toth: None. N. Schärer: None. J.J. Maguire: None. A.P. Davenport: None. J. Refardt: None. N. Dhaun: None. M. Christ-Crain: None. Introduction: Most cases of hyponatremia result from inappropriate arginine vasopressin (AVP) activity, leading to free water retention. The hormone apelin, secreted by the posterior pituitary, antagonizes AVP in salt and water homeostasis. Observational data in hyponatremic patients have not only shown an elevation in copeptin, a surrogate marker for AVP, but also a relative apelin deficit. The subcutaneous administration of apelin analogs in hyponatremic rodent models led to an increase in urine output and sodium levels, but data in humans are lacking. We hypothesized that restoring a physiological AVP/apelin ratio by intravenously administering exogenous [Pyr1]apelin-13 would increase urinary excretion in healthy in healthy participants with artificially-induced syndrome of inappropriate antidiuresis (SIAD). Methods: This is a double-blind randomized placebo controlled cross-over study involving 15 healthy adults who presented for a total of three visits. SIAD was induced with intravenous 4 µg desmopressin, oral water intake of 30 ml/kg body weight and subsequent infusion of 300 ml hypotonic (0.45%) saline. Thereafter, the study infusion with [Pyr1]apelin-13 in a concentration of 10 nmol/ml (high dose) or 1 nmol/ml (low dose) or placebo was administered during three hours in random order. Blood samples were taken every 30 minutes during the study infusion and every 60 minutes thereafter. Urine output was assessed every 60 minutes. The primary endpoint was the total urinary volume excreted from start to one hour after the end of infusion (4 hours in total). Secondary endpoints were changes in plasma sodium during the observation period of 9 hours. The analysis was conducted by fitting mixed effect models. Results: Seven of 15 participants were female (47%). Median [IQR] age was 26 years [24, 29] and median [IQR] body mass index was 23.2 kg/m2 [20.6, 27.5]. The primary analysis showed no difference in 4-hour urine output after infusion of either dose of apelin compared to placebo, i.e. mean 4-hour urine output was the highest during infusion of placebo with 173 ml (95% CI: 136 - 209) and 17 ml lower (95% CI: -52 - 19; p = 0.36) during low dose apelin and 15 ml lower (95% CI: -51 - 20; p = 0.40) during high dose apelin. In contrast, plasma sodium adjusted for sodium levels at the start of infusion significantly increased upon infusion of high dose apelin with +0.7 mmol/L (95% CI: 0.2 - 1.1, p < 0.01) over 4 hours and +1 mmol/L (95% CI: 0.5 - 1.4, p < 0.01) over the entire observation period. No differences in sodium were observed between placebo and low dose apelin. Conclusion: Intravenous apelin increases sodium levels in healthy volunteers with artificially induced SIAD, establishing it as a potential novel therapeutic option for SIAD. Presentation: Monday, July 14, 2025