IgA nephropathy (IgAN) is increasingly understood as a B-cell–driven disease. Class-switched B cells and the plasma cells they give rise to act as a kind of "B-cell factory," producing galactose-deficient IgA1, which forms circulating immune complexes that deposit in the glomeruli and drive kidney injury. As therapies targeting this pathway move into practice, many nephrologists are applying immunologic mechanisms outside their core training.

Samir Parikh, MD, of The Ohio State University Wexner Medical Center, discussed why B-cell biology warrants more attention in clinical education, why IgAN still lacks validated biomarkers, how he approaches treatment sequencing in the absence of combination-therapy data, and why earlier detection remains a central unmet need in IgAN care.

Q&A: Understanding the B-Cell Pathway in IgA Nephropathy, With Samir Parikh, MD

HCPLive: IgAN is increasingly understood as an immune-mediated disease involving multiple pathways. Which aspects of the disease biology do you think are most important for clinicians to understand today?

Parikh: I think one of the areas that is probably least well understood is the B-cell pathways that actually lead to the class switching and the production of galactose-deficient IgA1, and the plasma blasts and plasma cells that continue to produce them. Nephrologists by trade are not immunologists, but we are using immunologic drugs, and that pathway seems to be very key in the production of galactose-deficient IgA1 and then getting into circulation in the immune complexes. It's really important that we spend time focusing on educating on the B-cell factory, so to speak, that drives IgA production and the resulting IgA nephropathy.

HCPLive: As our understanding of the molecular drivers of IgAN becomes more refined, do you anticipate a shift toward more personalized treatment?

Parikh: I hope so. Right now, we don't have IgAN-specific biomarkers, and I think one of the hopes for the future—in the next five to ten years—is that we're able to identify specific biologic markers that can help inform disease. We have a lot of tools in the toolkit, but we don't know how to stratify who needs what. Having markers available that can potentially guide treatment decisions and explain the heterogeneity a little bit will be better for patients. That will allow us to say, based on your profile, these therapies will work best for you, and hopefully optimize outcomes—stabilizing or even improving kidney function over time.

With so many new therapeutic modalities emerging, how are you thinking about sequencing treatment for patients?

Parikh: We don't have all the answers to that because we don't have data on combination therapies yet. But we understand the mechanisms of disease, so you use the data available to you—biopsy, proteinuria, hematuria, GFR, patient factors—and ask what therapies would benefit this particular patient most, based on their overall profile. In most cases, that's going to begin with hitting the immunologic drivers of disease. You need to turn off that inflammation, but you also need to do things that are protective to the kidney and help slow the maladaptive changes that are happening. You can think about a profile where you're using endothelin receptor antagonists and RAS blockers to help control things in the kidney, but then also looking proximal to turn off the disease so we can arrest the process driving the damage in the first place. Our thoughts on this are going to evolve as more data come out and we get real-world experience with these combination therapies.

HCPLive: What is one change you hope to see in IgAN care over the next few years?

Parikh: In the short term, the biggest push we have to make is to recognize the disease earlier. We have to get in front of our primary care colleagues, our urologists, OB/GYNs, ER physicians, even our nephrology colleagues, to say hematuria is not benign—especially if it's glomerular hematuria. We need to evaluate that. I would love to see urinalysis become part of routine screening on physical exams. I would love to educate primary care that hypertension is not usually essential or primary, and we have to look for other causes when we see it, especially in younger populations. The workup is not expensive or extraordinary—it's very basic, it's just forgotten. Right now we're seeing patients way too late, coming to clinical attention at chronic kidney disease stage three or four. We want to recognize and see the disease sooner, because a lot of these patients are asymptomatic and may not present until they've accumulated a lot of chronic damage. So that's what I hope to see.

Reference

1. Barratt J, Floege J, Rovin BH, et al. Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV). Kidney Int. 2025. https://www.kidney-international.org/article/S0085-2538(25)00278-9/fulltext

2. Suzuki H, Kiryluk K, Novak J, et al. IgA Nephropathy: Core Curriculum 2021. Am J Kidney Dis. 2021. https://www.ajkd.org/article/S0272-6386(21)00598-9/fulltext