Ask AI
Back Back
Expert guidance in IgAN management
Expert Guidance in IgAN Management: Risk Stratification and Treatment Pearls

Released: June 24, 2025

Expiration: June 25, 2026

Pietro Canetta
Pietro Canetta, MD, MS
Activity Information

Activity

Continue to Activity
Key Takeaways
  • Proteinuria has become an important biomarker in the management of IgA nephropathy (IgAN), for determining progression risk and as a treatment goal, but research for other biomarkers continues.
  • Anticipated changes in IgAN management recommendations include lower proteinuria treatment goals and combined use of standard supportive care approaches with therapies that target immunological aspects of IgAN pathophysiology.
  • As key members on care teams for patients with IgAN, advanced practice providers (APPs) may have a range of responsibilities, such as follow-up visits to monitor treatment response, identification and management of adverse effects, and patient education.

In this commentary, Pietro Canetta, MD, MS, addresses questions posed by healthcare professionals (HCPs) during a live event titled, “A Shared Vision: Aligning Care at the Local Level to Improve Patient Outcomes in IgAN.” These questions highlight the need for expert guidance on matters related to managing patients with IgA nephropathy (IgAN), including use of biomarkers for risk stratification, comprehensive treatment strategies for integrating new and emerging therapies, and roles of APPs.

What biomarker(s) can be used to predict the risk of IgAN progression?
There are a few biomarkers that are clearly associated with disease progression. One is estimated glomerular filtration rate (eGFR), and that is kind of obvious, right? If a patient’s eGFR is low and the outcome of interest is low eGFR, then you are already there. However, it is important to educate patients that an initially low eGFR suggests that they have kidney disease that is already significant, and there is urgency in receiving treatment.

Hematuria is another biomarker in IgAN. Research has demonstrated an association between increased amounts of microhematuria and disease progression, but it is hard to quantify in practice. Conversely, intermittent gross hematuria has been associated with better outcomes. That may be because of the earlier identification of patients with IgAN. If patients are diagnosed earlier because of gross hematuria, they may have a lead time bias.

Proteinuria is a very important biomarker because it is predictive of IgAN progression, and it correlates with response to treatment. More specifically, changes in proteinuria in response to treatment tend to correlate with changes in outcome. Notably, because studies of different treatments have shown that, across study interventions, decreases in proteinuria are associated with improved outcomes, proteinuria reduction has also become important in the context of treatment goals. In fact, the FDA has allowed proteinuria to be used as a surrogate outcome in drug development. This has led to faster completion of clinical trials and accelerated approvals because, instead of waiting 5-15 years for kidney failure outcomes, proteinuria results are available more quickly. This change has helped move the field forward in developing new therapies that have a strong likelihood of benefit and in getting those therapies to patients.

Other markers, like tubular and serum biomarkers, are being studied. One example is neutrophil gelatinase-associated lipocalin (NGAL). None are ready for clinical usage in IgAN, but I look forward to having more biomarkers available in the future.

The International IgAN Prediction Tool is a good way to estimate IgAN prognosis. An HCP enters values for disease-related clinical criteria—including eGFR, proteinuria, and biopsy results—and the tool provides an estimated risk of 50% decline in eGFR or progression to end-stage renal disease over a specified time (eg, 5-7 years). It is freely available online and as an application. I find this to be a useful tool in helping patients understand what to expect with IgAN. I can use it in the office to show patients their estimated 5- to 7-year risk.

How do you approach patient care when there are discordant responses to treatment, specifically decreased proteinuria with increased creatinine?
The key is where the eGFR goes. The goal is to avoid a decrease in eGFR that leads to kidney failure. We know, though, that there can still be eGFR loss over time, even when proteinuria is low. In patients with decreased proteinuria but increased creatine, there is partial success because the proteinuria is being reduced. However, just because it is trending downward does not mean that the destruction has stopped. If you have a fire, and you put out 80% of the fire, the fire is still burning and doing damage.

In a case like this, I may consider another biopsy to get a better sense of disease activity, or I may consider switching or adding therapy. If I think the patient is already receiving a good treatment, I may add something that can help stabilize the disease. The challenge with eGFR is that it takes time to see it change, whereas proteinuria can increase or decrease quickly. That is why proteinuria is more useful as an immediate marker, while eGFR is the endpoint that we are working toward.

Does combining treatments that target different pathways improve outcomes or does it increase risk of overtreatment? How do you approach this issue?
The current Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for IgAN were published in 2021, and they are obsolete, in part because the FDA has approved several drugs for IgAN since 2021. Updated guidelines are expected to be finalized late in 2025, and it is useful to consider concepts from the 2021 guidelines and how they may be changing.

The 2021 guidelines focused on supportive care: managing blood pressure, implementing lifestyle modifications, and treating with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). Those approaches continue to be important components of IgAN management. The 2021 guidelines also recommend a proteinuria target of <1 g/day. I think we have realized that this is not low enough, and a careful reading of the literature supports reducing proteinuria as much as possible. Experts currently suggest a proteinuria goal of ≤0.3 g/day, and I think this will be reflected in the new KDIGO guidelines.

Even with the changing treatment landscape, managing IgAN as a chronic kidney disease is still very important and includes: addressing decreased GFR, proteinuria, edema, and high blood pressure; ensuring adequate diuresis and stable volume status; and focusing on beneficial lifestyle changes such as smoking cessation, weight management, and dietary sodium restriction.

However, in IgAN in particular, these treatment strategies must be paired with approaches that address the immunological aspect of the disease. I anticipate that the new guidelines will consider these approaches in parallel. This is where many of the new and emerging therapies will have a role. To tailor treatment to individual patient needs, multiple targeted treatments with different actions may be used together, some agents may be used temporarily, and others may be used in the long term.

A 2023 review on IgAN management, by Gleeson et al, proposed a treatment algorithm that outlines an approach to individualized patient care. Regimens start with supportive care, including lifestyle modifications (low-sodium diet, regular exercise, weight management), cardiovascular risk management (smoking cessation, lipid control), treatment with renin–angiotensin–aldosterone system (RAAS) inhibitors, and blood pressure control. The addition of an SGLT2 inhibitor is also suggested for patients with persistent proteinuria >0.5 g/day, which is lower than the treatment goal recommended in the 2021 KDIGO guidelines. Enrollment in a clinical trial is recommended for patients who have proteinuria ≥0.75-1 g/day after 3 months of optimized supportive care and are at high risk of progression. If clinical trial participation is not possible, the algorithm suggests other interventions, based on eGFR and risk assessment, including agents approved by the FDA since 2021. I think this algorithm is useful because it provides an updated way of thinking about IgAN management that addresses supportive care and immunological aspects of disease pathology and offers a framework that can help HCPs talk with their patients about benefit–risk profiles and individual tolerance for different treatment options.

How do you approach tapering of corticosteroids when switching patients to newer agents?
If I use systemic corticosteroids, I use them in a way that is very like the regimen used in the TESTING study. I use them for 6 months with 2 months up front at a higher dose and tapering off over the subsequent 4 months. At 6 months, I plan for patients to be done with the corticosteroid treatment, no matter what. If I use targeted budesonide, it is 9 months; at the end of 9 months, there is a 2-week taper, and then the course is done. This way, I do not worry about the need to taper because it is included in the regimen. If the patient and I decide to use a corticosteroid, the patient will complete the 6- or 9-month treatment course unless the steroid needs to be tapered off sooner because of tolerability or adverse effect considerations. In that case, a typical regimen for tapering corticosteroids should be used. But if the patient tolerates the corticosteroid, I will wait until the full course is completed to assess the effect on proteinuria before I consider another medication. At the end of the regimen, if proteinuria is insufficiently reduced, the decision may be made to switch to another medication. In that situation I do not spend more than 1-2 months before switching to or adding another agent.

It is worth noting that the risk of adverse events should be considered when deciding whether to use corticosteroid therapy. In the TESTING study the risk of the primary composite outcome (40% decrease in eGFR, kidney failure, or death due to kidney disease) was significantly reduced with methylprednisolone vs placebo, but the incidence of serious adverse events was greater with methylprednisolone, even when the maximum dose was reduced from 48 mg/day to 32 mg/day.

In a busy clinic, how do you decide when patients see a nephrologist vs an APP?
My clinic has APPs on staff, including a nurse practitioner who has extensive experience in caring for patients with glomerular diseases. We generally alternate visits. For a given patient, a decision about immunosuppression would be made with a nephrologist. Then once the treatment strategy has been identified, the nurse practitioner may see the patient for the next 1-3 visits to monitor how they are doing on therapy. When it is time to reassess and make another treatment decision, the patient will see a nephrologist again. I think APPs are very helpful with essential follow-through, such as managing patients’ symptoms, ensuring that their blood pressure is being controlled, supporting treatment approaches (eg, lifestyle modifications), and providing patient education.

Your Thoughts
Do you combine therapies that target immunological pathophysiology with supportive care in treating patients with IgAN? You can get involved in the conversation by answering the poll question and posting a comment below.

Continue to Activity

Poll

1.

Do you combine therapies that target immunological pathophysiology with supportive care in treating patients with IgAN?

Submit