Ask AI
Back Back
Questions on Treating IgAN

CE / CME

Ask the Expert: Your Questions on Treating IgAN in Clinic Today (Part 1)

ABIM MOC: maximum of 0.25 Medical Knowledge MOC point

Physician Assistants/Physician Associates: 0.25 AAPA Category 1 CME credit

Physicians: maximum of 0.25 AMA PRA Category 1 Credit™

Nurse Practitioners/Nurses: 0.25 Nursing contact hour

Released: December 21, 2023

Expiration: December 20, 2024

Pietro Canetta
Pietro Canetta, MD, MS
Richard Lafayette
Richard Lafayette, MD, FACP
CME/CE Information

Activity

Progress
1
Course Completed
Continue
Key Takeaways
  • In treating patients with immunoglobulin A nephropathy, Nefecon or targeted-release budesonide should be considered in those with features of substantial inflammatory disease and without rapidly progressive glomerulonephritis.
  • Targeted-release budesonide has a better safety profile than systemic glucocorticoids, even though neither have been directly compared with one another in a clinical trial.
  • Patients with stable creatinine and moderate proteinuria should receive 3 to 6 months of maximal supportive therapy.

Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis in the world. Further, it is estimated that approximately 30% to 40% of those with IgAN will progress to end-stage renal disease within 20 years. The initial treatment for patients at risk of progression is conservative treatment that is characterized by controlling blood pressure, using renin-angiotensin system (RAS) blockers, and prescribing lifestyle modifications like sodium restriction and exercise. Immunosuppressive treatment is often offered to those who do not respond to conservative treatment. More recently, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sparsentan (a dual endothelin and angiotensin 2 receptor antagonist), and Nefecon (targeted-release budesonide) have been added to the menu of treatment options and show promise in slowing IgAN disease progression.

In this expert commentary, I expand on answers to questions submitted by learners who viewed the “Experts on the Ground: Data Updated on Emerging Therapies for IgAN” learning module. Be sure to view part 2, as my colleague, Dr Pietro Canetta, provides answers to learner questions as well.

How frequently do you prescribe Nefecon (targeted-release budesonide)?

Richard Lafayette, MD, FACP:
My use of Nefecon is growing. I find it especially important to consider this agent for patients with features of substantial inflammatory disease who do not have rapidly progressive glomerulonephritis. These features include persistent hematuria with heavy (>1.5 g/day) proteinuria; M1, E1, and C1 lesions; and small increases in creatinine early in the disease course. In essence, I prescribe this therapy as a substitute where others would routinely use systemic steroids or other immunosuppressives.

Pietro Canetta, MD, MS :
I prescribe targeted-release budesonide to patients whose IgAN is more than mild but not severe and rapidly progressing. Historically, for those with aggressive disease (elevated proteinuria and active biopsies) and after maximizing the use of antihypertensives and RAS inhibitors, I prescribe systemic glucocorticoids. This requires thorough assessment of the risks associated with glucocorticoids and careful counseling with patients. Despite this proactive effort, many patients may still experience side effects from glucocorticoids, which are unpleasant at best and morbid (eg, infections, striae, and bone loss) at worst. 

In my clinical experience, targeted-release budesonide has a much more tolerable side effect profile than systemic glucocorticoids, even though neither have been directly compared in a clinical trial. Therefore, targeted-release budesonide is a good option for those who are concerned about the side effects of or may not be a good candidate for glucocorticoids (ie, diabetic or prediabetic, prone to infection). For very aggressive disease (high proteinuria, very aggressive features on biopsy, rapidly worsening estimated glomerular filtration rate [eGFR]), I lean toward prescribing systemic glucocorticoids, yet there is little evidence for making direct comparisons between these agents.

Can you discuss the timing of IgAN treatment in more detail?

Richard Lafayette, MD, FACP:
I remain traditional in that patients with stable creatinine and moderate proteinuria should receive 3 to 6 months of maximal supportive therapy, including a RAS inhibitor like sparsentan if they can tolerate it and an SGLT2 inhibitor if they have a reduced eGFR and ongoing proteinuria. You can then add agents like targeted-release budesonide if the RAS and SGLT2 inhibitor combination do not bring the patient into a low-risk setting. Earlier use of budesonide would be determined by the features previously mentioned: dropping creatinine that is associated with heavier proteinuria, active biopsy lesions, and perhaps influenced in the setting of ongoing hematuria.

Pietro Canetta, MD, MS :
I always start patients on an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker to get their systolic blood pressure under 120 mm Hg and then apply supportive measures (ie, smoking cessation, weight loss, and dietary counseling) to optimize their kidney health as needed. The length of time to determine response before escalating therapy depends on the patient. For example, many of my patients are otherwise young and healthy, and there is not much to optimize as far as supportive care. In these patients, the proteinuria response to blood pressure control and RAS inhibition might reach a nadir within 6 weeks, while in others there may be steady improvement with cumulative supportive care over 6 to 12 months.  

Regardless, if patients continue to have heavy proteinuria and other high-risk features despite this period of supportive care, I will typically offer a choice of systemic glucocorticoids, targeted-release budesonide, or clinical trial enrollment. If they are uninterested in or poor candidates for any of these choices, SGLT2 inhibitor to their treatment regimen. I differ from some colleagues here. Studies of SGLT2 inhibitors show that these agents are wonderfully safe and effective at reducing progression of kidney disease—but have only done so in patients who were not on immunosuppression therapy. I am not certain that these agents will be just as safe if used concomitantly with immunosuppression agents. If a patient opts for targeted-release budesonide or systemic glucocorticoids, they are only committing to a 6- to 9-month course of immunosuppression, so I will usually wait to introduce an SGLT2 inhibitor. Following another 6 months of treatment with an SGLT2 inhibitor, if patients continue to have substantial proteinuria and remain unenthusiastic about or ineligible for immunosuppression therapy, I may suggest treatment with sparsentan.

Is there a role for follow-up biopsy ?

Richard Lafayette, MD, FACP:
This is uncertain; however, it would be valuable to know in which setting each of the approved or upcoming novel agents are most effective. For example, are agents like Nefecon and B-cell inhibitors more effective in patients with more active inflammatory lesions than absent lesions and increased fibrosis? Will endothelin blockers work throughout the disease state of IgAN? Follow-up biopsies may be helpful in answering these questions and making treatment-related decisions. 


Your Thoughts?
What are your challenges in the management of patients with IgAN? Answer the polling question and get involved in the discussion by posting a comment below.

Continue

Poll

1.

What are your challenges in the management of patients with IgAN?

Submit