A phase 3 trial studying the effects of the vasopressin V2-receptor antagonist tolvaptan has found that the drug slowed the rate of decline in kidney function in patients with later stages of the most common form of polycystic kidney disease, a condition with no cure. The results were published online today (November 4, 2017) in the New England Journal of Medicine. The article is titled “Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease.” Autosomal dominant polycystic kidney disease (ADPKD) is an inherited condition that affects 1 in every 500 to 1,000 individuals in the U.S. This disease is found in all races and sexes. ADPDK, which is the fourth most common cause of end-stage kidney disease, ultimately requires dialysis or kidney transplant in many cases. The disease causes a slow but relentless growth of cysts that damage the kidneys. In addition to negatively affecting quality of life, the condition also causes hypertension and painful complications. The cysts, which can damage kidneys with their size, can also develop in other organs, especially the liver. Approximately half of individuals with ADPKD will eventually require dialysis or kidney transplant by age 60. The results of the trial demonstrated tolvaptan's ability to intervene in a way that slows kidney function decline in this population. Vasopressin promotes kidney-cyst cell proliferation and fluid secretion by means of up-regulation of adenosine-3′,5′-cyclic monophosphate (cAMP). The suppression of vasopressin production, release, or action by means of hydration, V2-receptor blockade, or genetic mutation has previously been shown to reduce cyst burden, protect kidney function, and prolong survival in rodent models.
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