Autosomal Dominant Polycystic Kidney Disease is a genetic condition effecting more than 1 in 1000 people.

It also called Polycystic kidney disease, or PKD. Effected individuals are born with numerous very tiny kidney cysts, which then progressively enlarge throughout life. This causes kidney damage, and often leads to end stage renal failure, with some people going on to receive dialysis or a kidney transplant. Over 90% have a mutation on chromosome 16 (PKD1) or chromosome 4 (PKD2). Patients with PKD1 experience a faster rate of decline in kidney function, and may face end stage renal failure before the age 60. Patients with PKD2 deteriorate more slowly, with some patients living well into their 70’s with good kidney function.


How is it treated?

From observational and animal studies a number of life style and other factors appear to influence cyst growth rate, and rate of decline of renal function. In addition, the drug Tolvaptan (Jinarc) is now available in Australia for selected patients.

Calorie restriction:
In animal studies, calorie restriction is associated with a slower rate of decline. In one large study in humans, it was shown that obesity was associated with faster rate of cyst growth

Salt intake:
Low salt diet in animals is associated with a slower rate of progression. This may be of benefit in humans. In human studies people with higher rates of salt excretion in their urine were shown to have faster rate of cyst growth. Sodium restriction reduces urine salt excretion, and may also help blood pressure control.

Blood pressure:
High blood pressure is common in PKD. Good blood pressure control influences PKD, and is important for overall health.

High fluid intake:
As a result of the drug Tolvaptan (Jinarc), we know suppression of antidiuretic hormone (ADH) slows the growth of kidney cysts and slows the decline of kidney function. ADH is naturally suppressed by drinking a lot of fluid, and this may slow cyst growth but it is not yet proven.

This is discussed elsewhere on our website, but it has been shown to slow cyst growth and help preserve renal function, and is now available in Australia.


Past and future Clinical trials

Laboratory research over recent years have revealed a number of pathways that are either up or down regulated in PKD. We are now seeing a number of existing as well as new treatments being trialled to target these pathways.

mTOR inhibitors:
These have been of benefit in animals, but the studies in humans have to date been limited by issues of toxicity and side effects from the treatment.

This common treatment for diabetes has the potential to suppress one of the key steps in the pathway that leads to cyst proliferation. In animal models there has been some efficacy. There may be a trial of this in Australia soon.

A pilot study of approximately 30 PKD patients showed this drug improved kidney function. The numbers are too small to draw significant conclusions. There is a global study of this new treatment (Bardoxolone) which will commence soon, with Australian patients being included. Our site will be one of the Australian centres and recruitment will hopefully commence later this year.

PPAR-alpha activators:
PPAR-alpha activators, which are currently used to treat Type 2 diabetes, have been trialled in mice models of PKD. In these studies cyst growth was slowed. There is currently a trial of one these agents, piolitazone, being conducted outside Australia.

Glucosylceramide synthase inhibitors (GCS inhibitors):
The cells in PKD cysts have been shown to accumulate glycosyphingolipids. GCS inhibitors interrupt that process, and animal studies of one of these compounds, have been shown to slow cyst growth. There is currently a trial of one these agents, venglustat, being conducted  http://clinicaltrials.gov/show/NCT03523728.

It is likely that drugs or treatments that alter the calcium level with the cells that line the cysts in PKD will be trialled in the future.