As the treatment landscape for IgAN continues to expand, clinicians are increasingly focused on identifying patients earlier, accurately assessing progression risk, and intervening before irreversible kidney damage develops.

In this Q&A, Ramy Hanna, MD, associate professor, disease expert, and clinical trial principal investigator in nephrology, discusses the challenges of early recognition in glomerular disease, evolving approaches to IgA nephropathy (IgAN) management, and the importance of timely evaluation to preserve kidney function.

Q&A: Early Detection and Treatment Advances in IgA Nephropathy, With Ramy Hanna, MD

HCPLive: What are some of the biggest challenges with recognizing glomerular diseases early, including IgAN?

Hanna: The problem with most glomerular diseases is that the only signs that you're going to have initially, and even into the medium term, are laboratory signs. You're going to have hematuria and proteinuria as the 2 cardinal signs, and that's early on.

Then, if you wait a little bit longer, you start to see a decline of kidney function. We call that GFR. We usually measure that through one of several measures, whether it be creatinine or cystatin C.

The problem is by the time that you actually have the decline in kidney function, it has been a long time — decades often — and when you look at biopsies, you see irreversible tissue death and fibrosis. So you're dealing with tissue that is no longer viable.

There are people walking around with 1000 mg of protein, 500 mg of protein. Those are significant biopsy thresholds. If they're not going to see a doctor, their doctor is not well informed, or they are not willing to undergo an invasive procedure for diagnosis, those patients are going to be missed.

The gold standard for glomerular diseases, most of them — not all of them at this point; there are a couple exceptions — would be kidney biopsy. It is an invasive procedure that does come with some risks. However, it is the only way to actually detect the immune involvement, and then in doing so, triage it, stage it, and plan treatment.

That's the problem. You have to catch people early. Patients have to go to the doctor. Their doctor has to be well informed. After that, they have to get a proper biopsy, and that's a lot of ducks to line up in a row. Sometimes those ducks don't line up perfectly.

HCPLive: What early warning signs should clinicians and patients be watching for, and when should a patient be referred to a nephrologist?

Hanna: There are 2 different sets of things you have to worry about as a patient.

I think patients need to look out for blood in the urine. That could actually be tiny little drops that we catch on a laboratory test. We catch 2 to 3 RBCs, or 4 RBCs, in a urinalysis, and that needs to be looked into.

In many cases, though, the urine will just turn bright red, and that obviously brings people in quickly. I imagine especially as a man, you see that and think, "Whoa, okay."

The other thing you look for is foam or protein in the urine. Now, I have to be careful because I have a couple cases in my mind of people who had organic acids, who were producing what looked like foam, or where the actual stream of urine was disrupting the water and CO₂ was mixing in and creating a panic.

I don't want to create a mass panic for everybody who generates foam in the toilet bowl. But if you are urinating into a steady collecting surface, like a cup when you provide a sample, or you're pretty sure you are not agitating the water as much and you are seeing lots of foam — almost like the head on a beer — realize that is what happens to protein when this process occurs.

It precipitates, and when it precipitates, it creates that head. That is when you think, "Okay, this is actually protein coming out of solution."

When you get that foam, or when you get blood in the urine, those are immediate warning signs.

Also, if you have chronic kidney disease and nobody knows why, that should prompt curiosity. I have a very high bar for physicians personally. We should be able to diagnose almost everything at this point. Not everything — there are always things beyond our ability to figure out — but we should make an effort to diagnose everything.

We can't cure everything. We should certainly try. And as physicians, we need to have the mindset of kidney success rather than kidney failure.

Editor’s Note: Hanna reports relevant disclosures with Alexion Pharmaceuticals, Novartis, AstraZeneca, and others.

References

1. Stamellou E, Seikrit C, Tang SCW, et al. IgA nephropathy. Nat Rev Dis Primers. 2023;9(1):67. doi:10.1038/s41572-023-00476-9.

2. Lee M, Suzuki H, Nihei Y, Matsuzaki K, Suzuki Y. Ethnicity and IgA nephropathy: worldwide differences in epidemiology, timing of diagnosis, clinical manifestations, management and prognosis. Clin Kidney J. 2023;16(suppl 2):ii1-ii8. doi:10.1093/ckj/sfad199.