Steroid treatment may lead to high risks for kidney disease associated with excess protein in urine
According to our new study published in the JAMA today, treatment with pills of the steroid methylprednisolone has been associated with an unexpectedly large increase in the risk of serious adverse events, primary infections among patients with IgA nephropathy and excess protein in their urine.
IgA nephropathy is a kidney disease that occurs when the antibody immunoglobulin A (IgA) lodges in the kidneys. It is one of the most common glomerular diseases in India. 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
Dr Vivekanand Jha, our Executive Director and one of the authors associated with the study says that:
”Up to 30 % 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”
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.
Vlado Perkovic, Executive Director of George Institute Australia and a lead author of the study says that:
“Although the results were consistent with potential renal benefit, definitive conclusions about treatment benefit cannot be made, owing to early termination of the trial”
A limitation of the study was that the recruitment was stopped earlier than planned because of excess adverse events and so the power of the study was less than predicted, and both risks and benefits might be overestimated. 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.
Our effort is to see that the treatment should produce benefit, but with no side effect or risk as was seen in the first phase. A series of steps are being taken to mitigate this risk in the second phase – this includes reducing the dose and giving it for a slightly longer duration, and use of prophylaxis against the common infections like TB, and lung infections.