New Delhi: According to a study conducted by The George Institute for Global Health and published in the JAMA, the treatment with pills of the steroid methylprednisolone was associated with an unexpectedly large increase in the risk of serious adverse events, primarily infections among patients with IgA nephropathy and excess protein in their urine.
The IgA nephropathy is a kidney disease that occurs when the antibody immunoglobulin A (IgA) lodges in the kidneys. It is one of the commonest glomerular diseases in India. “Up to 30 percent of all people with IgA nephropathy will eventually develop end-stage kidney disease. Decreased kidney function, persistent proteinuria, and hypertension are the strongest risk factors,” says Dr. Vivekanand Jha, Executive Director of the George Institute for Global Health, India, and one of the authors associated with the study.
Guidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, and they are widely used in these patients, but the benefits and risks have not been clearly established. In the study, participants with IgA nephropathy and proteinuria were randomly assigned to oral methylprednisolone (n = 136) or placebo (n = 126) for 2 months, with subsequent weaning over 4 to 6 months.
Recruitment was planned in several countries including China and India but after 2.1 years’ median follow-up, recruitment was discontinued because of an unexpectedly high rate of serious adverse events (including infections, gastrointestinal, and bone disorders). Serious events occurred in 20 participants (14.7 percent) in the methylprednisolone group vs 4 (3.2 percent) in the placebo group, mostly due to excess serious infections (8.1 percent vs 0), including two deaths. The primary renal outcome (end-stage kidney disease, death due to kidney failure, or a 40 percent decrease in estimated glomerular filtration rate [a measure of substantial loss of kidney function) occurred in 8 participants (5.9 percent) in the methylprednisolone group vs 20 (15.9 percent) in the placebo group.
“Although the results were consistent with potential renal benefit, definitive conclusions about treatment benefit cannot be made, owing to early termination of the trial,” says Vlado Perkovic of the George Institute for Global Health Sydney and a lead author of the study.
India is currently leading global recruitment in the follow up Low dose testing trial which will investigate how the benefit of treatment will be available to the patients without the risk. Eight Indian centres are participating.