Correlation of plasma copeptin and vasopressin concentrations in hypo-, iso-, and hyperosmolar states

Background: Copeptin, the C-terminal moiety of provasopressin, is cosecreted with vasopressin. Copeptin may be a useful parameter to characterize disorders of water homeostasis and can be readily measured in plasma or serum. However, it is unknown to date how circulating copeptin and vasopressin levels correlate at different plasma osmolalites. Objective: To correlate plasma copeptin with plasma osmolality and vasopressin concentrations in healthy subjects during iso-, hypo-, and hyperosmolar states. Methods: Plasma osmolalities, copeptin, and vasopressin levels were measured in 20 volunteers at baseline, after an oral water load, and during and after iv infusion of 3% saline. Correlation coefficients were determined between plasma osmolalites and copeptin and vasopressin concentrations, as well as between vasopressin and copeptin concentrations. Results: Median plasma osmolalities decreased from 290 mOsm/kg (range, 284-302) at baseline to 281 (273-288) mOsm/kg after water load and rose to 301 (298-307) mOsm/kg after hypertonic saline. Median plasma copeptin concentrations decreased from 3.3 (1.1-36.4) pm at baseline to 2.0 (0.9-10.4) pm after water load and increased to 13.6 (3.7-43.3) pm after hypertonic saline. Vasopressin and copeptin concentrations correlated with plasma osmolality (Spearman's rank correlation coefficient 0.49 and 0.77, respectively). There was a close correlation of vasopressin and copeptin concentrations (Spearman's rank correlation coefficient 0.8). Conclusion: Plasma vasopressin and copeptin correlate strongly over a wide range of osmolalities in healthy individuals. Therefore, the measurement of copeptin, which remains stable for several days, is a useful alternative to vasopressin measurements and will likely facilitate the differential diagnosis of disorders of water metabolism