Earlier this month, Kidney Disease: Improving Global Outcomes (KDIGO) released a clinical practice guideline regarding the management of immunoglobulin A nephropathy (IgAN) and immunoglobulin A vasculitis (IgAV). This 2025 version is a major update to the 2021 clinical practice guideline regarding the management of glomerular diseases. New insights and clinical trial results warranted this 2025 update, which is mostly relevant to IgAN.
The 2025 guideline encourages a more liberal kidney biopsy policy. It also suggests aiming for stricter proteinuria control, aiming for <0.5 g/d, ideally <0.3 g/d, and a stable estimated glomerular filtration rate. Additionally, a new concept to the 2025 update is to initiate treatment with therapies that prevent or reduce pathogenic IgA production and IgA/IgA and IgA/IgG immune complex formation along with therapies to manage the consequences of existing IgAN-induced nephron loss.
Today, we’re taking a look at a timeline of how the information in the 2021 guideline compares with the information in the newly released, 2025 guideline. The full text versions of each guideline can be found below.
Guidelines Referenced:
KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)
KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases
Major Changes and Key Takeaways (2021 – 2025)
Diagnosis of IgAN
Similar to the 2021 guideline, the 2025 update states that IgAN can only be diagnosed with a kidney biopsy. Additionally, there are no validated diagnostic serum or urine biomarkers for IgAN. The mesangial (M) and endocapillary (E) hypercellularity, segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T), and crescents (C) (MEST-C) score should be determined. Secondary causes should be excluded.
The 2025 update pushes for a more liberal biopsy policy, emphasizing the fact that to ensure early diagnosis and prompt treatment, a kidney biopsy should be considered in the case of every adult with proteinuria ≥0.5 g/d when IgAN is suspected.
Treatment of IgAN
For the 2025 update, the proteinuria goal was lowered to <0.5 g/d while on or off treatment of IgAN — ideally <0.3 g/d or equivalent. The 2021 goal was a reduction to <1 g/d.
Another major concept of the 2025 update is an emphasis on a dual and concordant focus on treatments that can prevent or reduce IgA-containing immune complex (IgA-IC) formation and IgA-IC-mediated glomerular injury, and manage the consequences of existing IgAN-induced nephron loss.
Targeted-release Budesonide (Nefecon) and Systemic Corticosteroid Therapy
A new recommendation supports the treatment of the immunologic aspect of IgAN to induce remission of the disease, with, where approved, a nine-month course of Nefecon for patients at risk of progressive loss of kidney function with IgAN with the caveat that data on the safety and efficacy of extended or additional courses are awaited.
Treating IgAN-Associated Chronic Kidney Disease
The 2025 guideline recommends that all patients with IgAN be treated with an optimized maximally tolerated dose of either an angiotensin II receptor blocker (ARB) or an angiotensin-converting enzyme inhibitor (ACEi). Exceptions to this recommendation include patients with contraindications such as low blood pressure, bilateral renal artery stenosis, or hyperkalemia, especially from advanced CKD.
Dual Endothelin-1 and Angiotensin II Receptor Blockade
Another recommendation new in the 2025 update suggests that where approved, patients at risk of progressive loss of kidney function with IgAN be treated with sparsentan, a dual endothelin angiotensin receptor antagonist. Sparsentan should replace a renin-angiotensin system (RAS) inhibitor (RASi), and not be prescribed together.
Sodium-Glucose Cotransporter-2 Inhibition
Another new recommendation suggests that, with a few caveats, patients at risk of progressive loss of kidney function with IgAN be treated with a sodium-glucose cotransporter-2 inhibitor (SGLT2i).
Pediatric IgAN
Following the 2025 International Pediatric Nephrology Association’s (IPNA) recommendations for the management of IgAN and IgAV in children, the 2025 KDIGO guideline mirrors its guidance, noting that more robust data in pediatric patients with IgAN and IgAV is needed.
Comparison of Recommendations
| Topic | 2021 | 2025 |
|---|---|---|
| Kidney Biopsy | The kidney biopsy is the “gold standard” for the diagnostic evaluation of glomerular diseases. However, under some circumstances, treatment may proceed without a kidney biopsy confirmation of diagnosis. | IgAN can be diagnosed only with a kidney biopsy, as there are no validated serum or urine biomarkers for the diagnosis of IgAN. |
| Diagnostic Serum and Biomarkers for IgAN | There are no validated diagnostic serum or urine biomarkers for IgAN. | There are no validated prognostic serum or urine biomarkers for IgAN other than estimated glomerular filtration rate (eGFR) and proteinuria. |
| Nefecon | Not addressed. | Nefecon is the only treatment to date proven to reduce the levels of pathogenic forms of IgA and IgA-containing immune complexes (IgA-ICs). We suggest treatment with a 9-month course of Nefecon for patients who are at risk of progressive loss of kidney function with IgAN |
| Proteinuria Goal | Therefore, reduction of proteinuria to <1 g/d is a reasonable target for interventions used in patients with IgAN who remain at high risk of progressive CKD despite maximal supportive care. | The only validated early biomarker to help guide clinical decision-making is urine protein excretion, which should be maintained at a minimum of <0.5 g/d (or equivalent), and ideally at <0.3 g/d (or equivalent), accepting that in some patients with extensive kidney scarring, this may not be possible and that multiple treatment strategies, including nonpharmacologic interventions, may be needed to achieve this. |
| Preventing/Reducing IgA-IC Formation | Not addressed. | Reduction or prevention of IgA-IC formation should incorporate treatments that have been proven to reduce pathogenic forms of IgA (commonly measured as galactose-deficient IgA1 [gd-IgA1]). Prevention of IgA-IC–mediated injury should incorporate treatments with proven anti-inflammatory and/or antifibrotic effects and ideally should be used in combination with, and not as a replacement for, treatments that prevent or reduce IgA-IC formation |
| ARB/ACEi | Not addressed. | 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) |
| Sparsentan | The phase 3 PROTECT study is evaluating the antiproteinuric and renoprotective effects of sparsentan in IgAN, a novel dual-acting angiotensin II and endothelin type A receptor antagonist. | We suggest that patients who are at risk of progressive loss of kidney function with IgAN be treated with sparsentan. |
| SGLT2i | Trials are also underway to evaluate the effect of sodium–glucose cotransporter-2 inhibitors (SGLT2i) on kidney and CV outcomes in nondiabetic kidney disease. | We suggest that patients who are at risk of progressive loss of kidney function with IgAN be treated with an SGLT2i. |
Sign up for alerts and stay informed on the latest published guidelines and articles.
Copyright © 2025, Guideline Central, all rights reserved.