Abstract
Tolvaptan is an orally active antagonist of vasopressin (antidiuretic hormone [ADH]) V2 receptors. By blocking water reabsorption in kidney collecting ducts, it prompts renal free-water excretion and has been used for the treatment of hyponatremia, both euvolemic due to the syndrome of inappropriate ADH secretion, and hypervolemic due to liver cirrhosis and congestive heart failure. In the past few years, it has been shown that vasopressin and its second messenger cyclic adenosine monophosphate (cAMP) play an important role in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). This has been the rationale for the use of tolvaptan to halt the progression of ADPKD, mainly through slowing kidney growth and decline in renal function. Two major randomized clinical trials have demonstrated the benefits of tolvaptan in slowing the progression of ADPKD in terms of kidney growth and decline in renal function at 1 and 3 years (REPRISE and TEMPO). However, the long-term effectiveness of treatment with tolvaptan remains to be determined.
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