Copeptin kinetics in healthy aging

Abstract Context The risk for disturbances in water homeostasis—resulting in hypo- or hypernatremia—increases with age. Age-related changes in arginine vasopressin (AVP) kinetics have been suggested, but findings are inconclusive due to challenges in quantifying AVP. Copeptin is a stable surrogate marker for AVP secretion, yet no data on age-related changes of copeptin kinetics are available. Objective We investigated copeptin kinetics in healthy ageing, hypothesizing a reduced within-subject range of copeptin in older individuals. Methods For this randomized controlled cross-over trial, 16 healthy older adults aged ≥60 years and 16 healthy younger adults aged 18-30 years were recruited. Participants underwent 1 copeptin stimulation test (infusion of 10 mL/kg of 3% saline in 60 minutes) and 1 copeptin suppression test (ingestion of 20 mL/kg tap water in 60 minutes) in randomized order. During both tests, copeptin was measured at baseline and at 15, 30, 45, 60, and 120 minutes. The primary outcome was the within-subject copeptin range in older adults compared with younger controls. Results Median (interquartile range) age of older adults was 67 (64, 72) years and 26 (23, 28) years in younger controls. In both groups, 50% were female. The within-subject copeptin range in older adults was 12.6 (8.5, 18.7) pmol/L and comparable with that of younger controls with 14.2 (8.5, 16.6) pmol/L (P = .867). While the copeptin response to stimulation was comparable between groups (β = +3.9 95% CI: −2.9, +10.7; P = .020 pmol·h/L for older adults), older adults exhibited a smaller decrease than younger controls during suppression (β = + .8 95% CI: +0.3, +1.3; P = .005 pmol·h/L). Conclusion Copeptin kinetics are mostly preserved in healthy older adults, yet the ability to suppress copeptin after hydration is diminished. This may contribute to the higher prevalence of hyponatremia in older individuals and should be considered in future fluid intake guidelines.