A new study suggests some drugs used to treat glomerular disease, such as calcium inhibitors and cyclophosphamide, are associated with an increased risk of cardiovascular complications. The results, published in
Kidney International, could help patients and doctors make more informed treatment decisions when taking long-term side effects into consideration.
Glomerular disease – also known as glomerulonephritis or GN – is a condition where abnormalities with the immune system damage the tiny filters in the kidneys that clean blood. Unfortunately, as the disease progresses and kidney function drops, this can lead to an increased risk of cardiovascular disease. However, some medications used to treat the disease – a class of drugs called immunosuppressants – are also associated with an increased risk of cardiovascular complications.
Dr. Sean Barbour, a researcher with the University of British Columbia’s Division of Nephrology, was interested in better understanding the influence of these immunosuppressants on cardiovascular outcomes in people with GN. He notes it’s a complex issue to disentangle.
“A drug may increase the risk of cardiovascular disease because it has some toxicity,” he says. “But due to its immunosuppressant properties, the same drug may also improve kidney function and reduce excessive amounts of protein in the urine (known as proteinuria), which in turn decreases the risk of cardiovascular disease.”
In their study, Barbour and colleagues analyzed data from more than 1,900 patients with GN living in British Columbia, taking into account which medications they took and their cardiovascular outcomes over an average period of seven years – for example if a patient experienced a heart attack or stroke. They looked at some of the common immunosuppressants used to treat GN, like prednisone, azathioprine, mycophenolate mofetil, calcineurin inhibitors and cyclophosphamide.
“Interestingly, we found that prednisone was not really associated with the risk of cardiovascular disease, despite the fact we thought it would be,” explains Barbour, noting this finding may be due to the fact that prednisone is usually only used for short-term treatment for the types of GN included in the study, and increased risk of cardiovascular events with this medication tend to occur with long-term use.
The results show that calcium inhibitors, such as tacrolimus and cyclosporine, were associated with up to a 3 times higher risk of cardiovascular disease, especially with long-term cumulative exposure. As well, each 10 grams of cumulative cyclophosphamide exposure was associated with 1.5 times higher risk of experiencing cardiovascular events.
Barbour cautions that while the risks associated with immunosuppressants may seem daunting, untreated GN will lead to kidney failure and the need for life-sustaining dialysis or a kidney transplant, resulting in worse outcomes and decreased survival rates.
Importantly, the study findings could help with selecting treatments. As Barbour notes, “If you have two equally effective therapies, you may want to pick the one that’s not associated with cardiovascular disease,” he explains. “Or, if you have to use one of the therapies associated with increased risk of cardiovascular disease, try to keep the exposure over time as low as possible – because the lower the exposure, the lower the risk.”
As a result of this study, Barbour says his team has received funding to develop a new prediction model that will help identify people with glomerular disease at high risk of cardiovascular complications.
