Immunoglobulin A nephropathy (IgAN) is the leading cause of chronic kidney disease (CKD) and kidney failure. The epidemiology, presentation, progression, and long term outcomes of IgAN vary greatly depending on patient ethnicity. For most patients significant nephron loss has already occurred by the time they are diagnosed making it important that therapy to preserve remaining nephrons be initiated as soon as possible.
Kidney Disease Improving Global Outcomes (KDIGO) systematically updates their guidelines in an effort to provide clinicians with the most current evidence based recommendations for the treatment of kidney disease worldwide.
Since their last update, there has been significant change in treatment recommendations for IgAN. Treatment can now target both of the drivers of nephron loss — the pathways leading to production of pathogenic forms of IgA and the intrarenal response to IgAN nephron loss, including the development of hypertension and proteinuria.
Let's review the major changes and key takeaways between the 2021 and 2025 guidelines regarding the treatment of IgAN.
Guidelines Referenced:
- KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases
- Chapter 2 IgAN/IgAV
- Publication: October 2021
- KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV) - Kidney International
- Publication: September 2025
Major Changes and Key Takeaways (2021-2025)
Angiotensin-converting enzyme inhibitor (ACEi)/ angiotensin receptor blocker (ARB):
- In 2021, recommendations for treatment of IgAN consisted primarily of supportive care aimed at managing high blood pressure and treatment of elevated proteinuria with an ACEi or ARB.
- Now, it is recommended that all patients with IgAN be treated with an optimized maximally tolerated dose of either an ACEi or ARB.
Glucocorticoids:
- In 2021, a six-month course of glucocorticoids was suggested for patients at increased risk of progressive CKD despite maximal support.
- Now, a reduced dose glucocorticoid regimen is suggested in settings where Nefecon is not available.
New Treatment Recommendations:
- Nefacon
- A nine-month treatment course is suggested for patients at risk for progressive loss of kidney function with IgAN.
- Nefecon suppresses mucosal IgA synthesis, and received approval from the U.S. Food and Drug Administration (FDA) in 2023.
- A nine-month treatment course showed significant reduction in proteinuria.
- Global approval and availability may vary.
- Sparsentan
- Sparsentan is a dual endothelin angiotensin receptor antagonist (DEARA). It combines a renin-angiotensin system inhibitor (RASi) with an endothelin antagonist in a single medication.
- Sparsentan received FDA approval for use in 2023.
- It can be used in patients with progressive loss of kidney function despite optimized maximally tolerated RASi.
- Sparsanten showed greater sustained reduction of proteinuria than with an ARB alone.
- Sodium-glucose cotransporter 2 inhibitor (SGLT2i)
- Use of a SGLT2i is difficult to generalize to patients with IgAN because trials included mostly older individuals with more advanced kidney disease, but may be considered for kidney disease with or without diabetes due to large scale trials showing good results for SGLT2i in CKD.
Other Therapies
- Another change since the 2021 guideline involved only Japanese IgAN, recommending tonsillectomy either alone or with pulsed glucocorticoids.
Pharmacologic Treatment of IgAN
| Agent | 2021 | 2025 |
|---|---|---|
| Nefecon | Not addressed. | We suggest treatment with a nine-month course of Nefecon for patients who are at risk of progressive loss of kidney function with IgAN. |
| Glucocorticoids | We suggest that patients who remain at high risk of progressive CKD despite maximal supportive care be considered for a six-month course of glucocorticoid therapy. The important risk of treatment-emergent toxicity must be discussed with patients, particularly those who have an eGFR <50 ml/min per 1.73 m2. | In settings where Nefecon is not available, we suggest that patients who are at risk of progressive loss of kidney function with IgAN be treated with a reduced-dose systemic glucocorticoid regimen combined with antimicrobial prophylaxis. |
| ACEi/ARB | We recommend that all patients have their blood pressure managed, as described in Chapter 1. If the patient has proteinuria >0.5 g/d, we recommend that initial therapy be with either an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB). | We recommend that all patients with IgAN be treated with an optimized maximally tolerated dose of either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB). |
| We recommend that all patients with proteinuria >0.5 g/d, irrespective of whether they have hypertension, be treated with either an ACEi or ARB. | ||
| Sparsentan | Not addressed. | We suggest that patients who are at risk of progressive loss of kidney function with IgAN be treated with sparsentan. |
| SGLT2i | Not addressed. | We suggest that patients who are at risk of progressive loss of kidney function with IgAN be treated with an SGLT2i. |
Other Therapies Evaluated in IgAN
| Agent | Suggested Usage 2021 | Suggested Usage 2025 |
|---|---|---|
| Antiplatelet Agents | Not recommended. | Not recommended. |
| Anticoagulants | Not recommended. | Not recommended. |
| Azathioprine | Not recommended. | Not recommended. |
| Cyclophosphamide | Not recommended. | Not recommended. |
| Calcineurin inhibitors | Not recommended. | Not recommended. |
| Rituximab | Not recommended. | Not recommended. |
| Fish Oil | Not recommended. | Not recommended. |
| Mycophenolate mofetil (MMF) | Chinese Patients: may be used as a glucocorticoid-sparing agent. Non-Chinese patients: Insufficient evidence to support use of MM. | Chinese Patients: may be used as a glucocorticoid-sparing agent. Non-Chinese patients: Insufficient evidence to support use of MMF. |
| Hydroxychloroquine | Chinese patients: In those who remain at high risk of progression in spite of optimized supportive care. Non-Chinese patients: there is insufficient evidence to support use. | Chinese patients: In those who remain at high risk of progression in spite of optimized supportive care. Non-Chinese patients: there is insufficient evidence to support use. |
| Tonsilectomy | Japanese IgAN: performed routinely (often with pulsed glucocorticoids). Chinese IgAN: Not routinely performed. Caucasian IgAN: Not performed. | Japanese IgAN: Tonsillectomy alone or with pulsed glucocorticoids is recommended in the Japanese Society of Nephrology guidelines for the treatment of patients with IgAN. Non-Japanese IgAN: Tonsillectomy should not be performed. |
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