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A New Paradigm in IgAN
A New Paradigm in IgAN Management: Expert Insights to Your Commonly Asked Questions

Released: December 18, 2025

Duvuru Geetha
Duvuru Geetha, MD
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Key Takeaways
  • Novel IgAN therapies were not studied in patients with an eGFR below 30 mL/min/1.73m2, a history of transplant, or secondary IgAN, so they cannot be used in these patient populations.
  • Despite the latest advances in treating IgAN, many questions remain unanswered, including guidance on tapering treatment, therapy duration, combination therapy use, and treatment sequencing.
  • All patients with IgAN should be referred to nephrology to confirm their diagnosis and ensure proper, guideline-directed treatment.

In this commentary, Duvuru Geetha, MD, answers questions posed by healthcare professionals (HCPs) during a live symposium titled “A New Paradigm in IgAN Management—Advancing Clinical Practice in the Era of Therapeutic Expansion.” Learn about the latest advances in managing patients with IgA nephropathy (IgAN), strategies to determine when to refer to nephrology or clinical trials, and what questions remain unanswered.

Many clinical trials include patients on optimized renin–angiotensin system (RAS) or sodium-glucose cotransporter 2 (SGLT2) inhibition. How does this influence the interpretation of the reported treatment benefit?
Any clinical trial evaluating new therapies must demonstrate benefit beyond these measures, only enrolling patients who are at risk for progressive disease (ie, persistent proteinuria) despite use of supportive care. Current clinical trials for IgAN, therefore, incorporate a run-in phase, during which patients receive optimized supportive care for approximately 12 weeks. Then they are rescreened to confirm eligibility based on the presence of persistent proteinuria prior to initiating the trial agent. These trials, whether they are placebo- or active-controlled, offer a glimpse into the decline in kidney function experienced by patients with IgAN who are receiving optimized supportive care and have residual proteinuria.

These trials have taught us some lessons. First, at least 66% of patients may not see a reduction in proteinuria below 0.75 g/day despite prolonged and intense RAS inhibition. Second, those with persistent proteinuria (ie, > 0.75-1.0 g/day) after adequate RAS inhibition see their estimated glomerular filtration rate (eGFR) decline sufficiently to cause kidney failure within their lifetime even after continuing RAS inhibition. Third, trials use the maximum tolerated, not maximum recommended, dose when requiring the control group to be treated with a specific angiotensin receptor blocker. Patients see less eGFR loss annually with the maximum tolerated dose. Although there are many lessons that we have learned, it is critical to compare novel therapies with the standard of care. That is how we will truly understand the benefits of new therapies.

What does the current evidence suggest about combination therapy or treatment sequencing in patients with IgAN?
There is not a clear answer to this question, but the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines recommend simultaneously addressing both the IgAN-specific drivers of nephron loss via immune-mediated immunomodulatory therapy as well as the generic responses to this nephron loss. At the same time, HCPs should begin supportive and immunomodulatory therapy. What we do not yet know is how to use the immunomodulatory therapies in combination either simultaneously or sequentially. Several are now FDA-approved, but the question remains regarding combination therapy and treatment sequencing in patients with IgAN.

How should HCPs approach therapy duration and tapering? Is there evidence for sustained remission after discontinuation?
This is another excellent question for which there currently is no answer. That is because patients’ IgAN can relapse after they discontinue treatment. The guidance on treatment duration is unclear, but it appears that repeat courses may be necessary for some. Again, we do not have evidence for tapering because no IgAN trial used a tapering regimen. I have a feeling that because IgAN is an immune-mediated disease like lupus nephritis or ANCA-associated vasculitis, we may need to approach treatment with remission induction and maintenance phases. This includes the use of  intensive immunosuppression to induce remission, followed by low-dose immunosuppression to keep patients in remission.

What are the limitations of the available trial data in terms of population diversity and comorbidities?
When you look at the baseline characteristics of the patients enrolled in the NefIgArd and PROTECT trials, approximately 64% to 76% of patients were White and only 22% to 33% were Asian. Yet it is well known that IgAN is common among Asian populations. Later trials like ORIGIN 3 and VISIONARY enrolled a higher proportion of Asian patients, so there are differences in that aspect.

Next, if you look at the trials’ inclusion criteria regarding biopsy, they did not require patients to complete a newer biopsy. For example, NefIgArd required patients to have biopsy verification within 10 years prior to screening. That is a problem when you are using immunomodulator therapy. Patients may have had a fresh lesion 10 years ago, but a repeat biopsy can show much chronicity with their disease. The trials also enrolled patients with persistent proteinuria of 1 g/day or a urine–protein-to-creatinine ratio (UPCR) of 0.8 g/day or higher. Therefore, in patients with a lesser degree of proteinuria, the efficacy and safety of these therapies are not known. Finally, each trial had a specific eGFR exclusion criterion. Most excluded patients with an eGFR less than 30 mL/min/1.73m2. Those of us in nephrology see a fair number of patients with an eGFR less than 30 mL/min/1.73m2, and we should be looking at treatment options for them as well. It is important to note that those patients were not included in the clinical trials and present a treatment gap. In addition, IgAN can recur in patients after kidney transplant, yet these patients were also excluded from clinical trials. So we do not have any data on using the new therapies in patients after kidney transplant either.

What are the most important patient-reported outcomes (PROs) or quality of life (QoL) measures that should be incorporated into both clinical trials and practice?
For IgAN, I do not think there are any specific PROs or QoL tools that are validated for this disease. Most HCPs use generic PRO tools like the SF-36, which covers the physical, psychological, and social aspects of life, as well as the PROMIS. There is a cross-sectional survey that was conducted in the US among adults with IgAN and their caregivers to evaluate the humanistic burden of this disease. It identified mental and physical health-related QoL impairments as well as increased levels of depression and anxiety as burdens of disease.

Trials should begin using the KDQOL-36 as well as some PROs from PROMIS, if possible. The PROTECT trial, for example, used the KDQOL-36, which showed that patients treated with sparsentan reported a lesser disease burden over time and trended toward improved health-related QoL vs those treated with irbesartan.

How can HCPs better identify and refer eligible patients for clinical trials?
This is important because of many ongoing trials in IgAN. Beginning with primary care, HCPs should educate patients about the recognition of proteinuria and hematuria and refer them to nephrology early. That is number 1. Next, nephrology HCPs should consider biopsy early. The KDIGO guidelines recommend kidney biopsy in patients with proteinuria at 0.5 g/day or more. Then there certainly are clinical trial databases like ClinicalTrials.gov that you can use to determine which clinical trials are ongoing or actively enrolling in IgAN.

Referral to academic centers with IgAN expertise is critical because of all the new therapies that we have. There is a lot to learn within a short period of time for community-based nephrology HCPs; it will be hard. Therefore, referrals to academic centers with glomerular disease expertise is important. If HCPs work for an institution that is actively enrolling patients in clinical trials, you should be able to use your electronic health record system for patient-specific matching based on the trial’s inclusion/exclusion criteria.

What practical barriers should HCPs anticipate when adopting new IgAN therapies in their practice?
Cost is always an issue, especially as new therapies enter the market. Sometimes there are resource limitations, especially in low- and middle-income countries. How do we make these expensive therapies available to these patients?

In addition, HCP unawareness of newly approved therapies or how to monitor for adverse events always presents as an issue. There is patient denial that HCPs must overcome with the use of any new therapy that may come to the market. For us, as HCPs, the real challenge is lack of real, validated biomarkers and personalized treatment for patients with IgAN.

Should primary care treat patients with IgAN or should patients always be referred to nephrology?
These patients should always be referred to nephrology because there is much need beyond supportive care that is required. The KDIGO guidelines recommend using both supportive care and immunomodulatory therapy simultaneously. I think nephrology should be the HCP to treat these patients’ IgAN.

A patient with a history of IgAN and renal transplant presents with proteinuria and hematuria. Does this mean that their IgAN has relapsed and what is their prognosis at this point?
IgAN can recur in patients after kidney transplant, but the only way to confirm that is by doing a biopsy on the transplanted kidney. That must be done to ensure you are dealing with recurrent IgAN and not another cause of proteinuria or hematuria. Indeed, if the patient has relapsed IgAN, they should be treated. But again, the new therapies were not tested in patients with a history of transplant. Therefore, you would treat this patient with corticosteroids, which we have been using for many years now.

If IgAN is on the differential, are there certain labs primary care should complete to get patients ready during the referral process?
Yes, primary care should order a urine analysis with microscopy because that will request dipstick proteinuria and hematuria on microscopy as well as a urine–albumin-to-creatinine ratio (UACR) and urine–protein-to-creatinine ratio (UPCR). Finally we need the measurement of serum creatinine and cystatin C, which allows us to estimate the GFR. Those 4 labs are required. Afterward, nephrology will order the biopsy and any additional tests to ensure nothing else (ie, secondary causes) is missing.

Your Thoughts
Have you kept up with the latest KDIGO guidelines for diagnosing and managing patients with IgAN? You can get involved in the conversation by answering the poll question and posting a comment below.

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