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 an algorithm to determine approaches to treatment of IgA nephropathy:

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

"I will, before getting to this algorithm comment that KDIGO has published the 2021 guidelines on glomerular disease, including a chapter on IgA nephropathy and as many who are listening to this probably realize that there is an update to that IgA chapter under creation. Just last month it was sent for public review and based on the feedback that the guideline organization likely will be updated to some degree and presumably published in early 2025. In the interim, several major thought leaders in the field have published really nice algorithms. Although, I will confess with the issue that everyone's struggling with, sort of which treatment to recommend in which situation. So let me just go through one of these from AJKD in 2024.

So beginning here with the diagnosis of primary IgA nephropathy, this excludes all the secondary causes of IgA nephropathy, as well as some of the rare manifestations like RPGN or minimal change disease from IgA. But in general, primary IgA, we use factors to assess the risk of progression and the most important of these factors is what's called the international IgA prediction tool, which I'll show you in the next slide. Patients are divided roughly into those at low risk, moderate, or high risk of progression. Those with low risk are people who would benefit more from supportive therapies and by supportive, what we're talking about here is intensive blood pressure control, maximization of RAS-Blockade, diet, lifestyle modifications, including smoking cessation.

In the individuals where the proteinuria declines and many authors differ at what level we should be aiming for, but let's say roughly 0.5 grams per day, that's considered an adequate response. And in those circumstances, we can continue maximal supportive care, possibly with the addition of an SGLT2 inhibitor to those with modest but not severe decline in GFR. You could see here recommended between 20 and 90. In people with more severe disease based on this risk prediction score or by assessment of proteinuria, individuals with either moderate or high risk of progression initially get treated with the same approach of RAS-Blockade, blood pressure control, et cetera. And those who have an inadequate response defined as not enough decline in proteinuria, then patients are first really encouraged to enroll in clinical trials. And I want to emphasize this point that we got to where we are in 2024 through clinical trials. Right now we have a lot of new agents that we're trying to tease apart which ones should be used in which circumstances and which patients. And the only way to get there is to get clinical trial data from our patients.

Additionally, there are a lot of new novel pathways and other exciting ways we may be able to treat IgA. So if we don't have our patients enroll in trials, we may have a difficulty knowing what the next step to take. And of course the challenge, and we'll see this with the patient that I discussed earlier, is convincing people to enroll in trials when there's already existing FDA approved treatments. So assuming someone is not interested in the trial or not eligible, if their GFR is less than 30, we want to continue the ACE inhibitor, perhaps introduce an SGLT2 inhibitor, if not present already. And we're really focusing on this hemodynamic side of things. And those with more preserved GFR, now we're thinking about the risk and benefit of different steroid therapies. Those who have not very severe inflammation findings on the biopsy and a lot of chronic damage, those people were probably going to cause more harm than good by treating them with steroids. And so that's a group where maybe no steroids is the right path to take. Additionally, we're all very familiar with the risks of steroids ranging from people with pre-diabetes becoming overtly diabetic, people with osteoporosis, having that get worse, infectious risks, obviously, are a big one. And so some of these factors might lead us to decide, no, this patient is not a good candidate for steroids.

And at that point we should consider sparsentan (Filspari, Travere Therapeutics), which is the dual endothelium angiotensin receptor antagonist and or SGLT2 inhibitors with the only caveat there that I don't believe there's much evidence of studying the combination in great detail. And individuals for steroids might be a good idea, these are those such as our patient with a relatively low risk of toxicity. And additionally in individuals with more severe levels of inflammation present on the biopsy, those are individuals where we can think about either the targeted release budesonide or Nefecon (Tarpeyo, Calliditas Therapeutics) as I'll describe in the next few slides, or reduced dose of corticosteroids."