John: There is considerable interest in innovative treatments for adult polycystic kidney disease, in particular those treatments that might interrupt the biological processes that lead to cyst formation and kidney failure. It is important, therefore, to have good evidence of the effects of these treatments and, in a July 2015 Cochrane Review, Davide Bolignano from Reggio Calabria in Italy and colleagues examined the relevant studies to assess the effects on patient outcomes. Here’s Davide to tell us more.

Davide: Autosomal dominant polycystic kidney disease is the most common inherited kidney disease and a leading cause of end-stage kidney disease. Patients suffer from the uncontrolled growth of cysts in kidney tissue, which cause bleeding, infection, pain, and high blood pressure. Progressive kidney failure results from the compression of healthy kidney by the cysts and tissue scarring.
Recent scientific advances have provided us with better understanding of the molecular pathways involved in kidney cyst growth but treatments for polycystic kidney disease remain non-specific. They seek to control symptoms, lower blood pressure, and prevent urine infections and flank pain. Several more specific treatments that target the biological events occurring during cyst formation have been proposed and are in early phases of testing, but have not reached use in clinical practice.
The clinical trials that have been done have generally been small and have tested such a wide range of treatments that it has been difficult to use the individual trials to guide clinical care. We have tried to help resolve this uncertainty by bringing all the trials together in our review, to look at the accumulating evidence comparing different treatments for adults with polycystic kidney disease on clinical outcomes, such as the need for dialysis and kidney failure. We included information from about 2000 patients with polycystic kidney disease, in 30 trials.
Eleven different treatments, lasting from a few days to five years have been tested and most trials did not have enough information to draw meaningful conclusions. The trials generally measured surrogate outcomes such as change in kidney or cyst size, blood pressure control, and the amount of protein in the urine; and we could not determine whether treatments had any impact on patient quality of life, kidney failure, or mortality. However, the trials did report on side-effects and these, such as thirst, dry mouth, diarrhea, infections, and mouth ulceration, were found for many treatments. The trials also had limitations in their methods which lowered our confidence in the findings and it’s possible that the true effects of treatment might be substantially different than those that have been reported.
Working through our findings, ACE inhibitors were not better than other treatments, such as angiotensin-receptor blockers or beta-blockers in protecting kidney function.
A single study was inconclusive about the effects of vasopressin receptor 2 antagonists on kidney function and cyst volumes, but did show that these drugs lead to thirst and dry mouth.
mTOR inhibitors had inconclusive effects on kidney function but led to soft tissue swelling, mouth ulcers, infections and diarrhoea.
And, finally, somatostatin analogues slightly improved kidney function in the short term but had uncertain long term impact on kidney function and caused diarrhoea.
In summary, the main message from our review is that there is a lack of evidence of any impact of the available therapies on the risks of kidney failure, but clear evidence that they cause specific side-effects. Overall, there is no good evidence to support the use of pharmacological treatment to protect kidney function in adults with polycystic kidney disease.
These findings have important implications for future research. Trials need to measure long-term outcomes such as dialysis or kidney transplantation, death, and quality of life. Highly pragmatic trials are required because polycystic kidney disease can be slowly progressive and the research will need to last several years. However, it would also be helpful if adults with polycystic kidney disease who have the highest risk of kidney failure and who might especially benefit from early intervention could be identified and included in these future trials.”

John: If you would like to find out more about the trials that have already been done, and watch for future updates of this review if new studies become available, visit Cochrane Library dot com and search for ‘polycystic kidney disease'.