Treatment for autosomal dominant PKD

Do we have any effective treatment options for patients with autosomal dominant polycystic kidney disease?

Runólfur Pálsson, MD: We have treatment options but they are not very effective. We do not have a proven treatment that can prevent kidney failure—we do not have studies that have end-stage renal disease as an endpoint.

However, we have studies that show that hypertension is an important factor influencing the progression of the disease. So the treatment of hypertension is important. Again, the target blood pressure is somewhat debated, but there are studies that show that lowering the blood pressure way below 140/90 mm Hg, below 130/80 mm Hg or even lower may be important. The focus should be on the treatment of hypertension, because most patients with autosomal dominant polycystic kidney disease have hypertension. It has been shown that using renin-angiotensin system (RAS) blockers, like angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), is beneficial. So that is something very important.

There are recent developments suggesting that treatments that reduce the growth of cysts or kidney volume may be important, particularly using vasopressin type 2 receptor antagonists such as vaptans, tolvaptan. This has been recommended in recent guidelines. I am not a strong believer in this treatment: we are talking about a long-standing treatment where the risk-benefit ratio is not that great because there are adverse effects of vaptans. Water loss because of excessive urination can result in dehydration. There are also adverse effects such as hepatic toxicity. The benefit does not appear to be that great with only surrogate markers being used in the trials that are being performed. But if you have a relatively young person with early chronic kidney disease that appears to be rapidly progressing, then there might be an option to try this treatment at least for some time in order to try to slow the progression of the disease.

The options in autosomal dominant polycystic kidney disease are unfortunately limited, but there is some exciting work going on in terms of trials at the moment.