Vasopressin in the Elderly: Physiological Changes in Neuroendocrine Function and Urinary Secretion in Healthy Aging

Vasopressin in the Elderly: Physiological Changes in Neuroendocrine Function and Urinary Secretion in Healthy Aging

Elderly people are at a high risk for disturbances in water homeostasis, with both hypo- and hypernatremia being more common with increasing age. Several changes in the physiology of the ageing body are responsible for this predisposition towards hypo- and hypernatremia, including diminished thirst perception, decreasing kidney function, and altered body composition. In addition, age-related changes in AVP secretion have been suggested, but findings remain inconclusive. Possibly, this controversy is due to measurement challenges of AVP.

Copeptin, a surrogate marker of AVP-release, is more stable and a reliable assay is commercially available. While copeptin stimulation and suppression has been studied in healthy volunteers, no study assessed possible changes in copeptin dynamics occurring with ageing.

Therefore, the aim of this study is to investigate copeptin levels in hypo- and hyperosmolar states in generally healthy elderly adults compared to young controls. The investigators hypothesize that both the suppression and stimulation of copeptin is impaired and that the overall range of variation is diminished with increasing age.

This is a monocentric open-labeled randomized controlled trial conducted at the university hospital Basel. All participants will be scheduled for a copeptin stimulation test using hypertonic saline infusion and a copeptin suppression test using water ingestion. The order of the two study visits will be randomized at study inclusion.

Inclusion Criteria:

• Age 18-30 years or ≥ 60 years
• Normonatremia (135-145 mmol/L)
• Plasma osmolality 280-300 mOsm/kg
• BMI ≥18 and ≤ 30 kg/m2

Exclusion Criteria:

• Regular use of medication with effects on water homeostasis (e.g. blood pressure medication, neuroleptics, desmopressin, etc.)
• Any severe disease requiring frequent medical care, except physiotherapy and/or psychotherapy
• Pacemaker or ICD
• History of thrombosis
• Active oncologic disease
• Heart failure
• Liver cirrhosis
• Estimated glomerular filtration rate (eGFR) < 60 ml/kg/1.73 m2
• Uncontrolled hypertension >160 mmHg systolic or >100 mmHg diastolic
• Polydipsia (ingestion of >3L fluids per day) and polyuria (>50 ml/kg urine production within 24 hours)
• Pregnancy or breastfeeding
• Participation in a study with investigational drugs within 30 days
• Acute illness
• Inability to follow study procedures