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Yet, the precise mechanism underlying the stimulatory effect of arginine on the vasopressinergic system remains elusive. Arginine plays a significant role in the urea cycle and increases the production of urea. An increase in plasma urea concentration raises blood osmolality, thereby possibly stimulating AVP release. We therefore hypothesized that the stimulatory effect of arginine on AVP may involve an increase in plasma urea levels.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>This analysis combined data from two prospective diagnostic studies. In total, 30 healthy adults (HA), 69 patients with AVP-D, and 89 patients with primary polydipsia (PP) underwent the arginine stimulation test. Infusion of arginine (L-\u00adarginine\u00ad-hydrochloride 21%) at a dose of 0.5\u00a0g\/kg body weight diluted in 500\u00a0mL of 0.9% normal saline was administered over 30\u00a0min. Blood was collected at baseline and 60, 90, and 120\u00a0min to analyze plasma copeptin and urea. The main objective was to investigate urea dynamics in response to arginine administration and its effect on copeptin release.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Plasma urea levels at baseline were comparable and increased 60\u00a0min after arginine infusion with a median (IQR) change of\u2009+\u20091.1\u00a0mmol\/L (+\u20090.8,\u2009+\u20091.5) in HA,\u2009+\u20091.4\u00a0mmol\/L (+\u20091.1,\u2009+\u20091.7) in patients with AVP-D and\u2009+\u20091.3\u00a0mmol\/L (+\u20090.9,\u2009+\u20091.5) in patients with PP. Concurrently, plasma copeptin levels substantially increased 60\u00a0min from baseline in HA (median change\u2009+\u20095.3\u00a0pmol\/L (+\u20093.2,\u2009+\u20098.8)) and in patients with PP (median change\u2009+\u20092.4\u00a0pmol\/L (+\u20091.2,\u2009+\u20093.8)), but remained stable in patients with AVP-D (median change\u2009+\u20090.3\u00a0pmol\/L (+\u20090.1,\u2009+\u20090.6)). Plasma urea and copeptin levels correlated the most in HA, with a Spearman\u2019s rho of 0.41 at baseline. Patients with AVP-D and PP showed only weak correlations of plasma urea and copeptin, with a correlation coefficient between 0.01 and 0.28.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>We demonstrate a slight increase in plasma urea levels in response to arginine, but plasma urea and copeptin levels were weakly correlated. Based on these findings, the stimulatory effect of arginine on AVP cannot be explained primarily by increasing urea levels.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11102-024-01489-7","type":"journal-article","created":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T18:33:14Z","timestamp":1737829994000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Relationship between plasma urea and copeptin in response to arginine stimulation in healthy adults, patients with vasopressin deficiency and primary polydipsia"],"prefix":"10.1007","volume":"28","author":[{"given":"Cihan","family":"Atila","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Lustenberger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irina","family":"Chifu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuele","family":"Ferrante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoran","family":"Erlic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana B.","family":"Drummond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Indirli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roosmarijn","family":"Drexhage","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew S.","family":"Powlson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Gurnell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Santana Soares","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes","family":"Hofland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Beuschlein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Fassnacht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Winzeler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie","family":"Refardt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirjam","family":"Christ-Crain","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,1,25]]},"reference":[{"key":"1489_CR1","volume-title":"Endotext","author":"M Christ-Crain","year":"2000","unstructured":"Christ-Crain M, Ball S (2000) The neurohypophysis: endocrinology of vasopressin and oxytocin. 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