Management of IgA Nephropathy
Appropriate treatment matters for patients living with IgA nephropathy
For patients with IgA nephropathy who are at risk of progressive kidney function loss, the Kidney Disease: Improving Global Outcomes (KDIGO) 2025 Clinical Practice Guideline for the Management of IgA Nephropathy recommends addressing both the consequences of nephron loss and preventing or reducing immune complex-mediated injury.1
Treatment goals and targets
Patients with IgA nephropathy who have proteinuria ≥0.5 g/day (or equivalent) are at risk of progressive kidney function loss and should start or escalate therapy.1
The goal of treatment is to slow kidney function decline to <1 mL/min per year.1
Proteinuria targets should be maintained at <0.5 g/d at a minimum, but ideally at <0.3 g/d.1 Clinical decision-making can be guided by urine protein excretion.1
Managing the responses to IgAN-induced nephron loss
Interventions for all patients with IgA nephropathy1:
- Lifestyle measures, where appropriate, including dietary sodium restriction (<2 g/d), smoking and vaping cessation, weight control, and regular exercise
- Blood pressure control to a target of ≤120/70 mm Hg
- Cardiovascular risk assessment with initiation of appropriate preventive interventions
Reduction of glomerular hyperfiltration and the impact of proteinuria with1,2:
- An optimized maximally tolerated dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) (GRADE: 1B)1,2
- Sparsentan (not to be used in combination with a renin-angiotensin system inhibitor [RASi]) (GRADE: 2B)1,2
- Atrasentan (an endothelin type A receptor antagonist; to be used in combination with a RASi)2
- A sodium-glucose cotransporter-2 inhibitor (SGLT2i) (GRADE: 2B)1,2
Sparsentan may be an appropriate first-line approach in contrast with the RASi-first approach because it1:
- Is a Dual Endothelin Angiotensin Receptor Antagonist (DEARA)
- Demonstrated greater proteinuria reduction and estimated glomerular filtration rate (eGFR) preservation in the Phase 3 PROTECT trial compared with maximum-labeled dose irbesartan
- Showed a comparable safety profile with maximum-labeled dose irbesartan
The guideline notes that measures to reduce glomerular hyperfiltration and the impact of proteinuria may include combination therapy approaches, such as first-line sparsentan or ACEi/ARB used together with an SGLT2i.1 Immunomodulation therapy should also be considered simultaneously as necessary.1
Preventing or reducing immune complex-mediated injury
Treatments that lower pathogenic forms of IgA are recommended in combination with anti-inflammatory and/or antifibrotic therapies1,2:
- A 9-month course of Nefecon is suggested (GRADE: 2B)1
- If Nefecon is unavailable, a limited course of a reduced-dose systemic glucocorticoids combined with antimicrobial prophylaxis is suggested (GRADE: 2B)1
- A proliferation-inducing ligand (APRIL) inhibitor directly acting on B-cells2
- Dual APRIL/B-cell activating factor (BAFF) inhibitors2
- Dual APRIL/BAFF inhibitors can reduce total immunoglobulins
Complement inhibitors may also be used because they mediate inflammatory glomerular damage and contribute to profibrotic activities in the tubulointerstitial compartment.2
Special situations, such as IgA nephropathy with nephrotic syndrome, acute kidney injury, rapidly progressive disease, pregnancy, or pediatric presentation, are addressed in detail in the full guideline.1
Footnotes
ACEi, angiotensin-converting enzyme inhibitor; APRIL, A proliferation-inducing ligand; ARB, angiotensin II receptor blocker; BAFF, B-cell activating factor; DEARA, Dual Endothelin Angiotensin Receptor Antagonist; eGFR, estimated glomerular filtration rate; IgA, immunoglobulin A; IgA-IC, immunoglobulin A-containing immune complex; IgAN, IgA nephropathy; KDIGO, Kidney Disease Improving Global Outcomes; RASi, renin-angiotensin system inhibitor; SGLT2i, sodium-glucose cotransporter-2 inhibitor.
- Kidney Disease Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. Kidney Int. 2025;108(Suppl 4S):S1-S71.
- Rovin BH et al. Kidney Int. 2026;DOI: 10.1016/j.kint.2026.03.003.
MA-DS-26-0033 | May 2026