Abdallah Geara, MD, is an Associate Professor of Clinical Medicine at the University of Pennsylvania.

Abdallah Geara, MD

2 IgA Nephropathy Experts Explain Clues For Early Intervention and Diagnosis

Two experts in nephrology are emphasizing the importance of identifying early clinical signs of IgA nephropathy (IgAN), often described as a silent disease.

“Clinicians should pay close attention to hypertension—especially in younger patients—and microscopic hematuria, again particularly in younger individuals,” said Corey Cavanaugh, DO, an academic nephrologist at the Cleveland Clinic, in an interview with HCPLive. “This is largely a young person’s disease, and it can be easy to explain these findings away or attribute them to something other than IgA nephropathy, since they’re relatively nonspecific. That’s why it requires a high index of suspicion and an astute clinician, particularly among non-nephrologists. It can be very subtle.”

Since these early findings are often attributed to benign or transient causes, diagnosis can often wind up delayed. By the time a majority of patients are diagnosed with IgAN, 50% to 75% have already progressed to chronic kidney disease (CKD) stage 3. At this point, eGFR falls below 60 mL/min/1.73 m² and structural kidney damage becomes irreversible, underscoring a need for earlier intervention. 

IgAN’s symptoms can be clinically silent before they progress to worsened stages, including non-visible hematuria, proteinuria, impaired kidney function, or hypertension. In one recent analysis, approximately 60% of IgAN cases were detected incidentally through hematuria or proteinuria identified on routine urinalysis. As a result, clinicians must rely heavily on measurable markers to assess disease activity and progression risk, with proteinuria remaining one of the most important indicators of long-term outcomes.

“When it comes to prognostication, we have to integrate clinical markers—serum creatinine, proteinuria, and hypertension—with demographic factors, including age and ethnicity, as well as histologic markers,” said Abdallah Geara, MD, Associate Professor of Clinical Medicine at the University of Pennsylvania, in an interview with HCPLive. “Bringing these together allows us to create a risk assessment for each patient, which then guides the next step in treatment. As therapies continue to evolve, the treatment algorithm has changed quite a bit over the last few years and will likely keep evolving.”

As the IgAN treatment landscape is experiencing a therapeutic revolution, this approach to risk stratification is becoming increasingly important. With 5 recently approved agents across distinct mechanistic pathways, therapeutic options are no longer the primary limitation. Instead, the focus is shifting toward earlier identification and precise risk assessment to ensure these therapies are deployed at a stage when they can have the greatest impact.

Editor’s Note: Abdallah reports relevant disclosures with Amgen, GlaxoSmithKline, Novartis, and others. Cavanaugh reports relevant disclosures with Otsuka Pharmaceutical Co, Novartis Pharmaceutical Corporation, Travere Therapeutics, and Vera Therapeutics.

Stoneman S, Teh JW, O’Shaughnessy MM. IgA nephropathy in adults. 

. Published online January 26, 2026. doi:10.1001/jama.2025.25020

Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. 

. 2021;100(4S):S1-S276. doi:10.1016/j.kint.2021.05.021

Videos

Corey Cavanaugh, DO, and Abdallah Geara, MD, separately share their perspectives on the clinical clues for IgAN diagnosis, including hypertension and microscopic hematuria.

Recent approval of 5 agents across distinct mechanistic pathways has redefined the 

treatment landscape, therapeutic options no longer remain the limiting factor, but the earlier identification and risk stratification needed to deploy them effectively.

In a majority of patients first presenting with IgAN, 50% to 75% have already progressed to 

 stage 3, signaling the unmet need for earlier identification before eGFR falls below 60 mL/min/1.73m² and structural kidney damage becomes irreversible. This same threshold marks the point at which the therapeutic window for emerging targeted agents narrows, and the opportunity for meaningful nephron preservation diminishes.

HCPLive spoke with Abdallah Geara, MD, an Associate Professor of Clinical Medicine at the University of Pennsylvania, to delve deeper into the current clinical landscape for IgAN.

: IgA nephropathy is often called a silent disease in its early stages, but are there subtle signs that clinicians might be overlooking, and what early clinical clues should prompt a closer look?

From the physician’s perspective, patients may not have many symptoms, if any. Hematuria is a big one; a young patient with hematuria is usually sent to urology for initial evaluation, which could be appropriate in some cases, but in the majority of young patients with hematuria, a nephrology pathology is responsible, IgA nephropathy, or membranous disease. So if a urology evaluation is negative, a nephrology evaluation would be an appropriate next step.

: Delayed diagnosis remains a challenge in IgAN. Where does the diagnostic process tend to break down, and what practical steps can help clinicians recognize and refer patients sooner?

The second question ties into the first; hematuria, with or without proteinuria, needs an explanation. If there is no good urological explanation, a nephrology evaluation might get us closer to a diagnosis. We know that 75% of patients with IgA nephropathy, when biopsied, already have established CKD stage 3 in the United States. Early diagnosis is something we still need to work on. We do not have any screening measures for IgA nephropathy, and urinalysis is not part of screening or health maintenance for the majority of patients. All of these steps, if implemented, can improve early diagnosis.

: Once IgAN is confirmed, how do you approach risk stratification? Which clinical features or biomarkers carry the most weight in shaping your management strategy?

When it comes to prognostication, we have to integrate clinical markers, serum creatinine, proteinuria, and hypertension with demographic markers, including age and ethnicity, and histologic markers. All three together allow you to create a risk assessment for the patient, and based on that risk assessment, you can decide what the next step of treatment should be. As therapy is evolving, the treatment algorithm has changed quite a bit over the last few years and continues to evolve.

 The treatment landscape has evolved significantly. Can you give an overview of the major therapeutic classes now available and what distinguishes them mechanistically?

The recently updated guidelines give a broad framework on how to treat IgA nephropathy, putting therapy into two big categories: therapy that addresses the chronic disease component, and therapy that addresses the inflammation caused by IgA nephropathy.

For the chronic disease component, we have RAAS blockade and SGLT2 inhibitors, as well as newer agents addressing the endothelin pathway, including sparsentan and atrasentan.

For the inflammatory or IgA-driven pathway, we have traditional therapies including corticosteroids, hydroxychloroquine, and newer, more targeted therapies including targeted-release formulations of budesonide, complement inhibitors like iptacopan, and, more recently, zigakibart, an anti-APRIL monoclonal antibody. Additional medications are expected to be approved to address this inflammatory component.

: How have you been deciding between newer targeted agents and traditional approaches? What about a patient's profile has been tipping the scale?

As we see more and more data, I'm more convinced that IgA nephropathy does require some level of IgA modulation. Using a complement blocker, targeted-release corticosteroid, MMF, or anti-APRIL will be required in the majority of patients. How to sequence these agents and which to start with is more based on the patient's profile and their tolerance. I try to shy away from corticosteroids, and all these other agents do carry some level of immune modulation that needs to be considered. Safety is very important when comparing these agents, as we do not have head-to-head comparisons. From an efficacy perspective, while proteinuria improvement is roughly similar across agents, there are also differences in eGFR slope that must be considered.

: Some therapies act on systemic immune pathways while others target mucosal immunity or downstream inflammation. How should clinicians think about these mechanistic distinctions when building a treatment strategy?

I do not have a unified treatment strategy as of now. I combine the immunosuppressive/modulator approach with the chronic disease approach. In general, the more targeted, the better. Even the more systemic approaches are relatively targeted; complement inhibitors and anti-APRIL therapy are directed at specific pathways, and clinical trials have shown these did not lead to many adverse effects, particularly around infections. Targeted release at the mucosal level might be ideal for someone at high risk of infection or corticosteroid side effects, though some systemic absorption does occur. This needs to be balanced against the more systemic immune modulation seen with complement inhibitors or anti-APRIL approaches.

: Looking ahead, where do you see the biggest gaps remaining in IgAN , whether in diagnosis, predicting disease course, or developing new therapies?

There is room for improvement across all of these areas. For diagnosis, we still rely on a kidney biopsy to confirm IgA nephropathy; we do not have a biomarker that helps with diagnosis, assesses response to treatment, or predicts long-term prognosis. For therapy, the newer treatments do offer improvement compared to where we were before, but we still need to understand how to use them, for how long, and what the clinical course will look like when therapies are combined or used sequentially. There is still a lot to figure out. The data we are generating is very exciting for both patients and physicians dealing with IgA nephropathy, but there is still a lot to learn.

Editor’s Note: Abdallah reports relevant disclosures with Amgen, GlaxoSmithKline, Novartis, and others.

Sharma I, Panta R. Emerging Therapies in IgA Nephropathy: From A Proliferation-Inducing Ligand (APRIL) and B-cell Activating Factor (BAFF) Inhibitors to Precision Medicine. 

. Published online December 22, 2025. doi:

Caster DJ, Abner CW, Walker PD, et al. Clinicopathological Characteristics of Adult IgA Nephropathy in the United States. Published online June 1, 2023. doi:

https://doi.org/10.1016/j.ekir.2023.06.016

Articles

Five recently approved agents spanning distinct mechanistic pathways have expanded IgA nephropathy (IgAN) therapy, shifting the primary unmet need toward earlier detection and risk stratification. Many patients are first diagnosed after substantial progression, with 50%–75% already at CKD stage 3, where eGFR <60 mL/min/1.73 m² limits nephron preservation potential. Persistent hematuria, with or without proteinuria, warrants nephrology evaluation when urologic workup is unrevealing. Treatment increasingly integrates chronic kidney protection with targeted IgA-driven immunomodulation.

Geara breaks down the clinical framework for the modern era of IgA nephropathy. 
