Travere Therapeutics
The Kidney Disease: Improving Global Outcomes (KDIGO) 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) provides updated evidence-based recommendations for clinicians worldwide.¹ Guidance is based on systematic evidence reviews and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.¹ ² These guidelines build upon the 2021 KDIGO Glomerular Diseases Guideline and integrate evidence from new randomized controlled trials and real-world data published through August 2024.¹
Diagnosis continues to rely on kidney biopsy, as no validated serum or urine biomarkers exist.¹ Prognosis is guided by validated tools such as the International IgAN Prediction Tool, which combines clinical and histologic data to estimate risk of kidney failure or major kidney function decline over time.¹ However, there are no validated prognostic serum or urine biomarkers for IgA nephropathy beyond eGFR and proteinuria.¹
Treatment goals emphasize slowing kidney function decline to <1 mL/min/year and maintaining proteinuria at <0.5 g/day at a minimum, but ideally <0.3 g/day.¹ To reach these targets, management focuses on the following complementary approaches.¹
Managing the consequences of nephron loss¹:
• Preventative interventions include lifestyle changes, cardiovascular risk reduction, and blood pressure control (target ≤120/70 mm Hg) may be introduced
• Therapies that lower glomerular hyperfiltration and proteinuria may be used
• Sparsentan may be an appropriate first-line approach in contrast with the renin-angiotensin system inhibitors (RASi)-first approach as it is a Dual Endothelin Angiotensin Receptor Antagonist (DEARA) and demonstrated greater proteinuria reduction and eGFR preservation in the Phase 3 PROTECT trial than maximally tolerated irbesartan
• Sparsentan or an ACEi/ARB may be used with or without sodium-glucose cotransporter-2 inhibitors (SGLT2i). Sparsentan and an ACEi/ARB must not be used together
Preventing or reducing immune complex–mediated injury¹:
• Therapies such as a 9-month course of Nefecon, or reduced-dose systemic glucocorticoids with antimicrobial prophylaxis (if Nefecon is not available), are suggested to reduce pathogenic forms of IgA
In summary, the KDIGO guideline recommends healthcare professionals consider strategies to both prevent or reduce immune complex-mediated injury, and manage consequences of nephron loss.¹ Combination therapy approaches, such as sparsentan or ACEi/ARB with an SGLT2i may be considered as part of this approach.¹ Immunomodulation therapy should also be simultaneously considered as necessary.¹
IgA nephropathy is the most common primary glomerular disease globally and remains a leading cause of kidney failure.¹ Despite advances in supportive care, many patients have historically experienced poor long-term outcomes.³ The 2025 KDIGO guideline marks a significant step forward by refining treatment aims, setting clear therapeutic targets, incorporating new therapies supported by recent clinical trials, and providing practical, evidence-based recommendations to improve patient care.¹
By emphasizing both prevention, or reduction of immune-mediated kidney injury, and management of progressive kidney function loss, the guidelines highlight how newer therapies can be incorporated alongside standard measures and lifestyle changes to improve outcomes for patients with IgA nephropathy.¹
References:
MA-DS-25-0107 | November 2025
The KDIGO Clinical Practice Guideline for the Management of IgA Nephropathy and IgA Vasculitis were updated. Read now.
This analysis studied the clinical and biopsy characteristics of adult IgA nephropathy cases across the United States. Learn more.
