Intravenous [Pyr¹]apelin-13 in Healthy Volunteers with Artificially-Induced Syndrome of Inappropriate Antidiuresis - a double-blind, randomised, placebo-controlled crossover study
Abstract Apelin, a hormone secreted by the posterior pituitary, antagonises arginine vasopressin in salt and water homoeostasis. Administration of apelin analogues increased urine output in hyponatremic rodent models, but corresponding human data are lacking. We therefore investigated intravenous [Pyr¹]apelin-13 in healthy participants with artificially induced syndrome of inappropriate antidiuresis. In this double-blind, randomised, placebo-controlled crossover study, 15 healthy adults (7 female; mean age, 28 years [SD, 8]) attended three study visits. Hyponatremia was induced using desmopressin, water loading, and hypotonic saline. Participants subsequently received high-dose [Pyr¹]apelin-13 (1800 nmol), low-dose [Pyr¹]apelin-13 (180 nmol), or placebo as a 3-hour infusion. The primary endpoint was cumulative urine output from infusion initiation until 1 hour after its completion. Neither apelin dose produced a clinically relevant difference in urine output compared with placebo. ClinicalTrials.gov: NCT06277336. Funded by the Swiss National Science Foundation. Registration number: NCT06277336 .
Authors
- Fiona A. Chapman (ORCID: https://orcid.org/0000-0002-9774-1643)
- Janet J. Maguire (ORCID: https://orcid.org/0000-0002-9254-7040)
- Robert Little (ORCID: https://orcid.org/0000-0003-1870-3241)
- Chiara Angela Bizzozero (ORCID: https://orcid.org/0009-0001-7042-4541)
- Martin Bidlingmaier (ORCID: https://orcid.org/0000-0002-4681-6668)
- D. Vogt (ORCID: https://orcid.org/0000-0002-0668-5675)
- Lorraine Bruce
- Anthony P. Davenport (ORCID: https://orcid.org/0000-0002-2096-3117)
- Mirjam Christ‐Crain (ORCID: https://orcid.org/0000-0002-6336-0965)
- Sven Lustenberger (ORCID: https://orcid.org/0009-0002-2091-8460)
- Neeraj Dhaun (ORCID: https://orcid.org/0000-0001-9128-6603)
- Sophie Monnerat (ORCID: https://orcid.org/0000-0002-0179-7889)
- Joyce Santos de Jesus (ORCID: https://orcid.org/0009-0000-9587-5421)
- Eszter Kustos-Toth (ORCID: https://orcid.org/0009-0005-7788-6158)
- Julie Refardt
Institutions
- University of Basel (CH)
- University of Cambridge (GB)
- Erasmus MC (NL)
- University Hospital of Basel (CH)
- Edinburgh Royal Infirmary (GB)
- LMU Klinikum (DE)
- The Queen's Medical Research Institute (GB)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-10-16
- DOI
- https://doi.org/10.1038/s41467-026-78333-y
- Primary Topic
- Apelin-related biomedical research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Universität Basel
- Universitätsspital Basel
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung