Glomerular Disease Clinical Case Review

In this video, Craig Gordon, MD, nephrologist at Tufts Medical Center and associate professor of medicine at Tufts University School of Medicine, discusses treatment options in this case of IgA nephropathy:

Editor’s note: The following is an automatically generated transcript of the above video.

"Here are the four hits. Hit 1, hit 2, hit 3, and hit 4. And represented in the various colors are treatments that are either FDA approved in green, those that are approved for other conditions, but could theoretically be used in IgA nephropathy in this yellow-orange color. And those that are under active investigation in the light blue color. So let me start by taking these in turn, it's never quite clear where to present the agents that have a renal protective effect. But for sure, individuals diagnosed with IgA nephropathy should be treated with maximal RAAS inhibition. And based on data from the DAPA-CKD study and the EMPA-KIDNEY study, a lot of these individuals with modest reductions in GFR should receive SGLT-2 inhibitors. But recently data has come to existence to show a benefit of endothelial receptor antagonists, including dual endothelium angiotensin receptor antagonists being beneficial as far as lowering proteinuria and potentially slowing the rate of decline in GFR in IgA nephropathy. So these are agents that we should think about in many of our patients, but if we're focusing on an immunological approach to trying to stop the disease process, we're going to start thinking about how to handle these various hits in the mechanism.

So I want to begin with hit 1, which is the production of the galactose-deficient IgA1 molecule, often in the terminal ileum. And a exciting advance has been the development of a time-released formulation of budesonide, which appears to impact the production and release of this galactose-deficient IgA1. And I'll show in a few slides, some data on the benefit of these agents on proteinuria and GFR. Should also emphasize that agents that impact B-cell pathways, including those that inhibit the APRIL and BAFF molecules, BAFF is B-cell activating factor, might also have a role in lowering the effect of this hit 1. And in fact, in phase II trials, there have been some encouraging data on these agents, both mechanistically as well as in reduction in proteinuria.

When one turns to later hits, hits 3 and 4, now we're talking about agents trying to reduce inflammation. The well-described agent that we've been studying for decades now are the use of systemically active corticosteroids with their sort of double-edged sword of pros and cons as far as, perhaps some treatment efficacy, but also some potential harms. But there's been exciting data being developed, looking at complement inhibition through various pathways, including the alternative pathway, the mannose and lectin binding pathway, and sort of terminal complement. And these are all under active investigation right now with a recent accelerated approval of iptacopan (Fabhalta, Novartis) as one of these potential treatments inhibiting complement factor B. So there's a lot of choices and one really needs to discuss with the patient and weigh the risks and benefits of these different approaches. And I'll come to this in one of a number of recent publications proposing different treatment algorithms."