This transcript has been edited for clarity.
Andrew S. Bomback, MD, MPH: Hi. My name is Andrew Bomback. I'm an associate professor of medicine at Columbia University Irving Medical Center and also the co-director of the Center for Glomerular Diseases at Columbia. It's really exciting today to talk to you about IgA nephropathy.
The most common question I get when someone is referred to me with IgA nephropathy is whether the patient should be treated with immunosuppression. Every nephrologist who sees a lot of IgA nephropathy has their own system in terms of deciding when to use immunosuppression. This is an increasingly important question because we're seeing more and more available medications to use that can suppress the immune system in IgA nephropathy. We no longer just are using corticosteroids. We have some newer therapies that have been approved by the US Food and Drug Administration, and we have a number of therapies in clinical trials that we're optimistic will be approved and will be able to use in the future.
So when to use those immunosuppressants is an important question. Some people rely on clinical parameters, and they specifically look at proteinuria. The proteinuria target has changed over the years. Ten or 15 years ago, I think most people would have said their threshold to use immunosuppression in IgA nephropathy was at about 1000 mg/d of proteinuria; that was mostly based on natural history studies as well as clinical trials that enrolled patients who had ≥ 1 g of proteinuria.
That threshold for proteinuria initiation has lowered, however. Many people have lowered it to 750 mg/d as the threshold to start immunosuppression, and the most recent data in IgA nephropathy from the RaDaR study suggest that you can even go down to 450 mg/d as your threshold, based on where they started to look at high risk for progression. So if you're going to use proteinuria, that's been a moving target.
There is, of course, the International IgAN Prediction Tool, which factors in proteinuria as well as other clinical parameters and biopsy parameters and can give you an estimate of your patient's risk for progression to end-stage kidney disease over a prespecified period of time. Many people use that risk prediction tool in practice while they're discussing the prognosis with their patient to justify using immunosuppression to modulate that risk.
For me, in 2024, the best way for me to decide on when to use immunosuppression remains the kidney biopsy itself. As you know, a kidney biopsy with IgA nephropathy undergoes what's called the Oxford Classification of IgA Nephropathy for each biopsy, where we get scores on mesangial proliferation, endocapillary proliferation, segmental sclerosis, tubulointerstitial scarring, and crescents (MEST-C). I look very closely at the MEST-C score to make a decision on who to immunosuppress and who should remain only on conservative therapy.
The presence of mesangial hypercellularity and M1 by itself does not tip me over to using immunosuppression, but if I see endocapillary proliferation, if the patient has an E1 score, that is very indicative to me that this patient should be immunosuppressed and has a good chance of responding to immunosuppression. The presence of crescents also would tip me over to using immunosuppression. A C1 score or a C2 score, which varies in terms of how many of the glomeruli have crescents, would also tip me over to using immunosuppression.
Conversely, too much scarring on a biopsy, regardless of the degree of inflammation, could push me away from using immunosuppression. So just having segmental sclerosis and S1 wouldn't, but if there was a T2 lesion, where there's more than 50% interstitial fibrosis, that makes me think very hard about whether I should be putting this patient on immunosuppression. Because what we know about those T2 lesions is that they almost invariably will progress to end-stage kidney disease.
Do I want to put this patient on immunosuppression to slow down what still appears to be an inevitable progression? Sometimes I do, but in many cases, if I see a T2 lesion, the decision on immunosuppression is made by that lesion, and the decision is made to not use immunosuppression.
To summarize, the way I use that Oxford score, the presence of an E1 lesion, a C1 lesion, or a C2 lesion is always pushing me toward using immunosuppression in my patients pretty much regardless of what the clinical parameters are.
Most of those patients will have significant proteinuria, which makes the decision easier. But if I see a tremendous amount of interstitial fibrosis, those T2 lesions, I have to think a little bit harder about whether to use immunosuppression in those patients. For those in whom I'm not using immunosuppression, I'm maxing out my conservative therapy with as high a dose of renin-angiotensin-aldosterone system inhibition as the patient can tolerate and typically adding on top of that an E2 inhibitor, which has been shown to slow progression in the chronic kidney disease caused by IgA nephropathy.
Thank you very much for taking a few minutes with me to talk about IgA nephropathy and a crucial question in terms of managing IgA nephropathy patients.
Medscape Nephrology © 2024 WebMD, LLC
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: A Common Question in Treating IgA Nephropathy: When to Use Immunosuppression - Medscape - Apr 18, 2024.
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