It has long been uncertain whether the benefits of treating IgA nephropathy, an immune-related form of kidney disease, with steroids outweigh the risks. However, a recent, large-scale study published last May with JAMA finally offers more definitive evidence. The results suggest that treating IgA nephropathy with a six-month course of low- to moderate-dose steroids can safely reduce the amounts of permanent kidney damage patients will experience.
IgA nephropathy is a form of kidney disease that’s caused when an antibody called immunoglobulin A (IgA) builds up in the kidneys, causing damage. Steroids are a form of medication that can reduce immune activity, and therefore mitigate some of the damage that IgA nephropathy causes in the kidneys.
However, most studies of steroids in IgA nephropathy to date have been relatively small and were completed before more conventional treatments for kidney disease – such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers or blood pressure control measures – became standards of care. As well, steroids can involve difficult and sometimes harmful side effects.
“Importantly, those previous studies did not as rigorously capture side effects, so there remained this huge uncertainty around whether the risk of steroids is worth the potential benefits when you add them to conventional therapies,” explains Sean Barbour, an Assistant Professor at the University of British Columbia’s Division of Nephrology who specializes in IgA nephropathy research and is also chair of the BC Renal provincial Glomerulonephritis (GN) Committee.
To gain more clarity on the issue, Barbour, in collaboration with researchers around the world – including in Australia, India, China and Malaysia – conducted a more large-scale, multi-centre investigation into benefits and risks of steroids as part of the TESTING trial. A total of 503 patients with IgA nephropathy at high risk of kidney function decline were given the treatment with methylprednisolone or a placebo.
At the beginning of the study, patients in the treatment group were given higher doses of methylprednisolone, but the study was temporarily halted due to safety concerns reported in a similar study being done in Germany at the time. The TESTING trial then resumed, but patients entering the study at this later point were given lower doses of methylprednisolone.
The results show that people receiving the lower dose benefited from the treatment just as much as those who received higher doses, but experienced significantly fewer side effects. Barbour notes that these results could open the door to a more effective treatment for patients earlier on in the course of their disease, reducing the amount of damage to their kidneys.
He also notes that IgA nephropathy is known to vary greatly across ethnic populations, and so Barbour and his colleagues wondered if patients’ responses to steroids would also vary by ethnic population. However, this multi-centre, multi-ethnic study showed that methylprednisolone was beneficial for all patients, irrespective of their ethnicity.
“That’s a very important finding because if you’re working somewhere like here in Vancouver, which is more multi-ethnic, it’s good to know that steroids will likely be just as beneficial for all of your patients,” notes Barbour.