What is the effect of vasopressin (Antidiuretic Hormone (ADH)) on the kidneys?

Vasopressin Effects on the Kidney

Vasopressin (ADH) primarily increases water reabsorption in the kidney collecting ducts by triggering the insertion of aquaporin water channels into the luminal membrane, allowing water to flow from the tubule lumen to the hypertonic medullary interstitium, resulting in concentrated urine. 1, 2, 3

Primary Mechanisms of Action

Water Reabsorption

• Vasopressin binds to V2 receptors on the basolateral membrane of collecting duct cells 1, 2
• This binding initiates a cascade involving:
  • G-protein activation
  • Adenylyl cyclase activation
  • cAMP production
  • Protein kinase A stimulation
• The final result is exocytic insertion of aquaporin-2 (AQP2) water channels into the luminal membrane 1, 3
• Water then flows through AQP2 in the apical membrane and through constitutive water channels (AQP3 and AQP4) in the basolateral membrane 1
• This process enables the formation of concentrated urine with osmolality typically >300 mOsm/kg H₂O 1

Sodium Handling

• Vasopressin has a significant V2 receptor-dependent antinatriuretic effect 4, 5
• It increases sodium reabsorption in the collecting duct by:
  • Increasing the activity of the epithelial sodium channel (ENaC) 2, 5
  • Increasing the abundance of the beta and gamma subunits of ENaC 6
  • Enhancing sodium reabsorption in the thick ascending limb via the Na-K-2Cl cotransporter (NKCC2) 6
• This sodium reabsorption is critical for maintaining the corticomedullary osmotic gradient necessary for maximal water reabsorption 5

Pharmacological Properties

• Vasopressin stimulates antidiuresis via V2 receptors coupled to adenyl cyclase 7
• At lower concentrations typical for the antidiuretic hormone, vasopressin inhibits water diuresis via renal V2 receptors 7
• The volume of distribution is approximately 140 mL/kg 7
• Clearance of vasopressin is 9-25 mL/min/kg in patients with vasodilatory shock 7
• The apparent half-life at clinical levels is ≤10 minutes 7

Clinical Implications

Pathophysiology

• In congenital nephrogenic diabetes insipidus, there is resistance to vasopressin action due to mutations in either the V2 receptor (AVPR2) or the AQP2 gene 1, 4
• This results in inability to concentrate urine, with urine osmolality usually <200 mOsm/kg H₂O 1
• Patients present with polyuria, polydipsia, and risk of dehydration 1

Therapeutic Considerations

• Vasopressin analogues (dDAVP) are used as replacement therapy for central diabetes insipidus 2
• V2 receptor antagonists like tolvaptan are used for treating hyponatremia in heart failure and SIADH 2
• Vasopressin analogues should be avoided in patients with ADPKD as they may accelerate cyst growth 1

Important Caveats

• Overdosage of vasopressin can lead to water retention and hyponatremia 2
• Elderly patients and those with renal impairment require careful dosing and monitoring 2
• Vasopressin is contraindicated in moderate to severe renal impairment (creatinine clearance <50 mL/min) 2
• Vasopressin may contribute to chronic kidney disease progression through effects on mesangial cell proliferation, renin secretion, and renal hemodynamics 2, 8
• In heart failure, vasopressin activation contributes to salt and water retention, potentially worsening congestion 1

Understanding the renal effects of vasopressin is crucial for managing fluid and electrolyte disorders, particularly in conditions like diabetes insipidus, heart failure, and hyponatremia.