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We are studying a condition called Autosomal Dominant Polycystic Kidney Disease (ADPKD). It is the most common inherited kidney disorder and affects 1 in every 800 people in the United Kingdom (12.5 billion people worldwide). The faulty gene that causes the condition is passed down between generations, with an affected parent having a 50% chance of passing on the gene to their child. Commonly people with ADPKD have multiple affected family members. In ADPKD cysts develop in both kidneys at a very early age. They are essentially non-cancerous fluid filled sacs. Over time the cysts grow in size and number, compressing much of the normal healthy kidney tissue. To put this into perspective, a normal kidney is roughly the size of your fist, however a polycystic kidney can be as large as a rugby ball. The resultant kidney damage progresses over the years and by the age of 60 years old, more than half of those affected develop kidney failure and require kidney replacement therapy in the form of dialysis or a kidney transplant. VASOPRESSIN Vasopressin is a hormone produced by the brain. Its role is to maintain the body’s water balance. In states of dehydration it acts on the kidneys to conserve water and produce concentrated urine. If the body is well hydrated, the body stops making vasopressin and dilute urine is produced. Research has shown that in polycystic kidney disease, the vasopressin hormone acts in an abnormal way. It drives the cysts to grow, so there are many more cysts and causes more fluid to collect inside them so they grow even bigger. We think that by getting people with ADPKD to drink large quantities of water, they can produce dilute enough urine to stop the body making vasopressin. By switching off the vasopressin signal in the body, this may slow down the progression of the kidney damage in ADPKD in the long term (see diagram). So far this theory has been shown to be true in rats with polycystic kidney disease, where getting them to drink three times their normal daily amount slows down the growth of cysts and kidney damage. However, until now there have been no research studies to prove whether this is also true in humans.

High water intake sends a signal to the brain that the body is well hydrated. In response to this the brain stops making vasopressin. The result of less vasopressin in the body is that the kidneys produce lot of dilute urine, and more importantly cysts growth may slow down which will slow progression of ADPKD to kidney failure.