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IgAN and New Treatments
A Healthcare Professional’s Perspective on the Evolving Understanding of IgA Nephropathy and New Treatments

Released: November 02, 2023

Expiration: November 02, 2024

Silvia Titan
Silvia Titan, MD, PhD
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Key Takeaways
  • Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis in the world.
  • We now can identify those at risk of CKD progression, and all patients with IgA at risk of CKD progression should receive conservative treatment.
  • More recently, SGLT2, endothelin inhibitors, and targeted-release budesonide (Nefecon) have been added to the menu of treatment options for those with residual proteinuria.

Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis in the world. It is estimated that approximately 30% to 40% of those with IgAN are at risk of chronic kidney disease (CKD) progression. Treatment for those at risk initially is based on conservative treatment, which is characterized by controlling hypertension, use of RAS blockade, and lifestyle modifications. Immunosupressive treatment is offered for those not responding to conservative treatment. More recently, SGLT2, endothelin inhibitors, and targeted-release budesonide have been added to the menu of treatment options for those with residual proteinuria. Expanded understanding of pathophysiology has led to the development of novel therapeutic agents for the management of IgAN, which has a high economic burden and impact on quality of life for patients. Based on their roles, managed care pharmacists are well positioned to enhance patient access to novel therapies for IgAN, facilitate communication with other healthcare professionals on the management of IgAN, and improve adherence to treatments.

This expert commentary, provided by Silvia Titan, MD, PhD, expands on answers to questions that learners submitted during the satellite symposium at AMCP Nexus 2023 on new and emerging IgAN treatments.

Is it an oversimplification to say that IgAN is an autoimmune disorder?
I think it is an oversimplification in the sense that although there is an autoimmune component to the disease, the occurrence of the disease is dependent on other steps that are not autoimmune. Once the IgA deposits occur in the kidney, there are very specific mechanisms that trigger inflammation and changes in the phenotypic architecture of the glomeruli that mediate disease progression and CKD. We need to understand all the steps and figure out where exactly we should target treatments to have a true impact in the disease. For example, we think that dysregulation of the intestinal microbiome may affect IgAN progression. However, even if we successfully regulate the microbiome, we may not considerably change the disease outcome if the IgA deposits still happen and all the other processes are still free to go. You will still have progression to CKD.

Is there any reason to consider IgAN treatments for other causes of proteinuria?
Yes, that is important. Glomerulonephritis can have many different causes, but treatment for CKD across different etiologies shares similarities. Let’s start by saying that every time I see hematuria and proteinuria, I have a differential diagnosis in mind. IgAN is always going to be one of the top candidates because we know that it is one of the most common causes of primary glomerulonephritis. When I see signs of glomerulonephritis in a patient, I will do a workup and will likely end up doing a kidney biopsy. Once I have the diagnosis, I can offer treatment options for my patients.

When treating IgAN, we typically start with conservative treatment. The rationale for that comes from what we know about mechanisms of progression and treatment for CKD in general: RAS blockade, blood pressure control, salt restriction, etc; these are all fundamental for CKD treatment in general. Other agents being added to conservative treatment—SGLT2, endothelin inhibitors, and other medications currently being tested in clinical trials—also work in CKD of different etiologies.

What biomarkers should be added in 2024 for better identification of IgAN that currently are not included?
Several candidates are being researched—including urinary biomarkers related to inflammation, biomarkers of complement activation, and assays on Gd-IgA—but more research is needed before those are implemented in clinical practice.

What differentiates the targeted-release budesonide (Nefecon) from other formulations?
Because of chemical properties of the capsule, the drug will not release until it is in the distal ileum area.

Have there been any head-to-head studies of targeted budesonide compared with methylprednisolone?
No, although a study like that would be very useful for healthcare professionals. The problem when you have several options but no head-to-head comparisons is, “Which one do I pick first?”

Would an endothelin receptor antagonist such as bosentan have any utility as an adjunctive therapy?
The only endothelin inhibitor currently approved for IgAN is sparsentan. It is possible that other endothelin inhibitors that are selective for receptor A have a similar effect, but these studies need to be done.

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