Antidiuretic Hormone and Serum Osmolarity Physiology and Related Outcomes: What Is Old, What Is New, and What Is Unknown?

Abstract

AbstractContextAlthough the physiology of sodium, water, and arginine vasopressin (AVP), also known as antidiuretic hormone, has long been known, accumulating data suggest that this system operates as a more complex network than previously thought.Evidence AcquisitionEnglish-language basic science and clinical studies of AVP and osmolarity on the development of kidney and cardiovascular disease and overall outcomes.Evidence SynthesisApart from osmoreceptors and hypovolemia, AVP secretion is modified by novel factors such as tongue acid-sensing taste receptor cells and brain median preoptic nucleus neurons. Moreover, pharyngeal, esophageal, and/or gastric sensors and gut microbiota modulate AVP secretion. Evidence is accumulating that increased osmolarity, AVP, copeptin, and dehydration are all associated with worse outcomes in chronic disease states such as chronic kidney disease (CKD), diabetes, and heart failure. On the basis of these pathophysiological relationships, an AVP receptor 2 blocker is now licensed for CKD related to polycystic kidney disease.ConclusionFrom a therapeutic perspective, fluid intake may be associated with increased AVP secretion if it is driven by loss of urine concentration capacity or with suppressed AVP if it is driven by voluntary fluid intake. In the current review, we summarize the literature on the relationship between elevated osmolarity, AVP, copeptin, and dehydration with renal and cardiovascular outcomes and underlying classical and novel pathophysiologic pathways. We also review recent unexpected and contrasting findings regarding AVP physiology in an attempt to explain and understand some of these relationships.