Unlocking Early Detection of IgA Nephropathy: The Critical Role of Timely Diagnosis 

Announcer:
You’re listening to On the Frontlines of IgA Nephropathy on ReachMD. On this episode, we’ll discuss the importance of diagnosing IgA Nephropathy early with Dr. Suneel Udani, who's a consulting physician with NANI, Nephrology Associates of Northern Illinois and Indiana and the Medical Director of NANI Research.

Here’s Dr. Udani now.

Dr. Udani:
We’re learning much more about the importance of early identification of IgA nephropathy, specifically because we have a better understanding of what the long-term prognosis looks like. And specifically, we have data from a study called RaDaR, the Rare Disease Registry out of the UK, and in that registry, we are seeing what the outcome for many patients with IgA nephropathy is. First is, they’re diagnosed in their second, third, or fourth decade of life, and with current interventions at the degree of proteinuria that many of them have, that their prognosis, unfortunately, is not very good long-term, meaning that most of them, if not all of them, will develop end-stage kidney disease and require dialysis and/or transplantation. That’s one aspect of it.

So the goal, of course, is to say, “Okay, can we then identify them at an earlier state?” because the manifestation that we’re seeing—the urine protein increase, their proteinuria,  as we call it—is partially reflective of active inflammation, which, of course, is treatable, and we’re hoping to find better treatments for that. But it also represents some degree of irreversible injury: scar tissue formation. So we’re oftentimes surprised by kidney biopsies in individuals who are young where their blood test and laboratory testing indicate that their kidney function is so well reserved. Their serum creatinine is in the normal range, and their EGFR is in the normal range, but on kidney biopsy, they actually have a fair amount of glomerulosclerosis and tubulointerstitial fibrosis and atrophy, which suggests that there is some irreversible injury. And that is, of course, manifesting as the things that we’re seeing: urine blood, urine protein, etc. So that tells us that we’ve missed part of the window in terms of when we should be identifying these folks because there’s already been injury occurring. So that, paired with the idea that their long-term outlook isn’t very good at the current state of care, tells us that there’s a good possibility we’ve missed an opportunity to identify and intervene early.

As we identify individuals early on, we are then forced to think, “What do we do with them?” And that is also a challenge because up to this point, we have had limited therapeutics particularly to change the inflammatory part of IgA nephropathy. I refer to the two ways we treat IgA nephropathy as disease-modifying, which potentially targets the actual inflammatory process and IgA molecules and their process of injuring the kidney versus supportive care or foundational care, which is where we use agents that are generally kidney-protective but are going to be particularly helpful for patients with IgA nephropathy because of the scarring injury that I alluded to before. And so those interventions help protect the healthy kidney from additional strain and damage.

So as we identify individuals earlier on, we hope that there is less scar and there is more injury that we can target. If we see that, it doesn’t mean we don’t still utilize those supportive measures, like RAS inhibition, endothelin receptor antagonist, sodium-glucose transport inhibitors, etc., but it means that perhaps the need for that will be less over the long term and that as we treat the inflammation, there may be less injury and scar tissue that ultimately develops.

We’re still far from a perfect approach though. We’ve had one drug receive full FDA approval that we think is immunomodulatory, i.e. a targeted budesonide. We’ve had another drug that has received accelerated approval, iptacopan, which targets the alternative complement pathway, which may also reduce inflammation. But there are also many other therapies that are currently in trial. And so some of this is going to be just ongoing evolution of how we approach this, but we still believe that early identification can at least provide us a better road map of how to approach each patient in a more individualized and personalized way.

Announcer:
That was Dr. Suneel Udani talking about the importance of an early IgA Nephropathy diagnosis. To access this and other episodes in our series, visit On the Frontlines of IgA Nephropathy on ReachMD.com, where you can Be Part of the Knowledge. Thanks for listening!