IgA nephropathy (IgAN), also known as Berger’s disease, is a chronic kidney condition caused by abnormal immunoglobulin A (IgA) antibodies triggering inflammation. For years, treatment primarily involved managing symptoms with blood pressure medication and lifestyle adjustments. However, recent advancements have introduced targeted therapies designed to directly address the underlying immune dysfunction driving the disease – offering new hope for patients at risk of kidney failure.
The Problem with Traditional Treatments
Traditional treatments like ACE inhibitors and ARBs help lower kidney pressure and reduce protein leakage, but they don’t stop the immune process causing damage. Steroids, while effective, come with significant side effects due to their broad immunosuppressive effect. This is why targeted therapies represent a major shift in how IgAN is managed: they focus on intervening in specific disease mechanisms, minimizing systemic effects.
Budesonide: A Targeted Steroid Approach
In 2021, the FDA approved targeted-release budesonide (Tarpeyo), a steroid formulated to release its active compound in the small intestine where abnormal IgA antibodies are produced. This localized action reduces inflammation at the source, decreasing antibody circulation to the kidneys. Clinical trials showed a 31% reduction in proteinuria after nine months, slowing kidney function decline over two years.
Eligibility: Adults with primary IgAN at high risk of kidney worsening, confirmed by persistent proteinuria (at least 1g/day) despite optimized supportive care.
Cautions: Avoid NSAIDs and certain medications (ketoconazole, ritonavir, erythromycin) that interfere with budesonide metabolism. Common side effects include swelling, high blood pressure, and weight gain.
Sparsentan: Blocking Kidney Inflammation
Approved in 2023, sparsentan (Filspari) takes a different approach. It blocks two receptors in the kidneys – endothelin type A (ETA) and angiotensin II type 1 (AT1) – reducing inflammation and protein leakage. Clinical trials showed a 45% reduction in proteinuria after 36 weeks and slowed kidney function decline over two years.
Eligibility: Adults with primary IgAN at risk of worsening kidney function, particularly those intolerant to steroids or SGLT2 inhibitors.
Cautions: Combining sparsentan with ACE inhibitors/ARBs or other endothelin blockers can cause dangerously low blood pressure. Monitor kidney function closely if taking NSAIDs. Not recommended during pregnancy.
Atrasentan: Focused ETA Receptor Blockade
Approved in 2025, atrasentan (Vanrafia) focuses solely on blocking ETA receptors in the kidneys. This reduces inflammation and lowers proteinuria without broad immune suppression. Studies showed a 38% reduction in proteinuria compared to placebo.
Eligibility: Adults with primary IgAN at risk of faster disease progression, with a urine protein-to-creatinine ratio (uPCR) of 1.5g/g or higher despite standard care.
Cautions: Avoid certain antibiotics and antifungals that interfere with atrasentan metabolism. Not recommended during pregnancy.
Iptacopan: Targeting the Complement System
The FDA approved iptacopan (Fabhalta) in 2024, targeting the complement system, a part of the immune system that drives inflammation in IgAN. By blocking a specific step in this system, iptacopan reduces inflammation without broadly suppressing immunity. Clinical trials showed a 38% reduction in proteinuria after nine months.
Eligibility: Adults with primary IgAN at high risk of faster disease progression, with a uPCR of 1.5g/g or higher.
Cautions: Requires vaccinations against meningococcal, pneumococcal, and Haemophilus influenzae type b infections. Not for use during active bacterial infections.
Sibeprenlimab: Blocking IgA Production
The newest FDA-approved therapy, sibeprenlimab (Voyxact), approved in November 2025, blocks APRIL, a protein involved in abnormal IgA antibody production. Unlike the others, this therapy is administered by injection.
These newer treatments are expanding treatment options for people with IgAN and giving many people more ways to slow kidney damage.
Conclusion: Targeted therapies are revolutionizing IgA nephropathy treatment by addressing the disease’s root causes while minimizing systemic side effects. These advancements offer hope for slowing disease progression and preserving kidney function for patients who previously faced limited options.
