John: Renal vasculitis causes damage to the small blood vessels inside the kidneys and – when untreated – leads to a rapid loss of kidney function. Therapies that block the immune system to switch off the vasculitis process are available but can lead to serious infections and other long term complications. As vasculitis is uncommon, it has been difficult to establish the most effective and safest treatment, because studies have often been too small to detect these effects reliably. One way to try to overcome this, is to combine the results of similar studies and, in September 2015, Giles Walters and his colleagues in Australia did this by updating the Cochrane Review of studies of treatments to induce and maintain disease remission for renal vasculitis. Giles tells us what they found in this podcast.

Giles: As John said, renal vasculitis leads to inflammation of small blood vessels and can cause permanent kidney failure and death. Before effective treatments, mortality from renal vasculitis was often 80%. Now, with modern therapies, 80% of affected people survive beyond 5 years. As renal vasculitis is caused by an immune reaction to blood vessels, most treatments act to suppress the immune system. Historically, treatment has centered around steroids and cyclophosphamide with plasma exchange added when severe kidney failure is present. More recently, more targeted drugs have been used, because the immune cells producing antibodies (B cells) that have what’s called the CD20 signature may have a central role in the disease process. Once treatment induces disease remission, the intensity of treatment is scaled back – and longer-term, less potent therapies are used to maintain the remission.
Despite recent developments in treatment, more than one in ten people with severe renal vasculitis still die in the first year after their diagnosis, and half of these deaths are caused by treatment side-effects. In the 2008 Cochrane Review, 13 studies were available involving 700 adults. These earlier studies were generally of low quality but plasma exchange added to other treatments seemed to provide some protection against end-stage kidney disease and continuous use of cyclophosphamide instead of monthly pulsed therapy prevented the disease from relapsing. However, whether treatments had important differences in side-effects was not clear from the available evidence.
By 2015, many more studies were available. Our updated reviewnow includes 31 studies involving over 2200 adults. The more recent studies tended to be bigger and more rigorous and used stricter disease definitions, aided by the activities of trans-national research groups. However, despite this progress, the studies collectively still had important design limitations which continue to give us low confidence in some results.
Plasma exchange was studied in about 200 people. When added to usual therapies, it may reduce the risk of developing total kidney failure with the need for dialysis at 12 months being halved, but there is no evidence that it affects mortality or the incidence of serious infections. Other studies, involving nearly 300 people, found that intravenous pulse cyclophosphamide may lead to disease relapse more often than continuous oral cyclophosphamide, but whether pulse or continuous cyclophosphamide had different impacts on death, need for dialysis or severe infection was very uncertain.
Evidence for the CD-20 monoclonal antibody, rituximab, was of higher quality. This drug was probably equivalent to cyclophosphamide, leading to most patients achieving disease remission by 6 months, without evidence that serious infection rates were increased. Mycophenolate is similar to cyclophosphamide as a therapy for inducing remission, but whether remission is sustained and relapse can be avoided by mycophenolate is still unclear.
Finally, when considering the maintenance of disease remission, azathioprine was as effective as cyclophosphamide, but mycophenolate mofetil is still not proven as effective when compared with azathioprine, and should be considered third line therapy.
To sum up, adults with renal vasculitis and severe kidney failure are less likely to need dialysis when plasma exchange is added, but there is little information about the impacts on death or infection. Continuous cyclophosphamide reduces disease relapse, and azathioprine is equivalent to cyclophosphamide for maintaining remission. Looking to the future, studies are now needed that focus on treatment toxicities and therapies for patients with milder forms of vasculitis.

John: You can find full details of this review, including all the included studies, online in the Cochrane Library. Simply go to Cochrane library dot com, and type in a search for 'renal vasculitis'.