An Evolving Landscape: NKF Addresses Critical Questions in IgA Nephropathy

IgA nephropathy (IgAN) is entering a period of rapid therapeutic change. 

In response to the evolving treatment landscape in IgAN, the National Kidney Foundation (NKF) hosted two scientific workshops in spring 2026: The Future of Clinical Trials in IgAN, held April 22-24 in Washington, DC, and B-Cell Therapies for Treating IgAN, held May 14-16 in Dallas, Texas.

The Evolving IgAN Treatment Landscape

While considered a rare disease, IgAN is the most common primary glomerulonephritis worldwide and a significant risk factor for kidney failure^1,2. The pathogenesis of IgAN follows the “four-hit hypothesis” (Table 1). Kidney injury in IgAN results from both disease-specific immune mechanisms and the downstream effects of nephron loss that are common to all forms of CKD^3,4.

Table 1. The “Four-hit hypothesis” in IgA Nephropathy

Hit 1	Excess production of galactose-deficient IgA1 (Gd-IgA1) by mucosal B-cells
Hit 2	Generation of autoantibodies against Gd-IgA1
Hit 3	Formation of Gd-IgA1-containing immune complexes
Hit 4	Immune complex deposition in the glomerular mesangium, triggering inflammation, fibrosis, and nephron loss

Recent advances in drug discovery, combined with the adoption of proteinuria as a surrogate endpoint for regulatory approval^5,6, have accelerated the development of new therapies for IgAN. Since 2021, three treatments have received full FDA approval to slow kidney function decline, and three have received accelerated approval to reduce proteinuria in IgAN. This momentum is also reflected in the growing number of therapies now in early- and late-phase clinical trials⁷. 

Updated KDIGO Clinical Practice Guidelines for IgAN

These developments prompted the publication of the KDIGO 2025 Clinical Practice Guidelines for IgAN⁸ and subsequent 2026 KDIGO Commentary on complement inhibitors and B-cell-modifying agents for IgAN⁹ and NKF/KDOQI US Commentary on the guideline with perspectives for implementation within the context of clinical practice in the United States¹⁰. The new guidelines represent a significant update to the KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases¹¹, in which optimized supportive care was the only available treatment approach for IgAN.

The updated KDIGO guidelines recommend a simultaneous, two-pronged treatment approach (Figure 1). One component focuses on disease-specific therapies that prevent or reduce IgA-containing immune complex formation and immune complex-mediated glomerular injury. The other approach focuses on managing the downstream consequences of IgAN-induced nephron loss through optimized CKD therapy. Importantly, the guidelines state that both approaches should be considered simultaneously in all patients.

Figure 1. KDIGO Two-Pronged Treatment Approach for IgA Nephropathy

Table 2. Newly Approved Treatments for IgA Nephropathy

Brand Name (Generic)	Approval Date (for IgAN)	Approval Type*	Target/Mechanism**
Tarpeyo (targeted-release budesonide)	Dec 2023	Full	Hits 1-3: Targeted-release corticosteroid acting on mucosal B-cells to reduce production of pathogenic IgA1
Filspari (sparsentan)	Sep 2024	Full	Hit 4/Optimized CKD Therapy: Dual Endothelin-A & Angiotensin II type 1 receptor antagonist (DEARA)
Fabhalta (iptacopan)	Aug 2024	Full	Hit 4: Complement factor B inhibitor, inhibitor of the alternative complement pathway
Vanrafia (atrasentan)	Apr 2025	Accelerated	Hit 4/Optimized CKD Therapy: Selective endothelin A receptor antagonist
Voyxact (sibeprenlimab)	Nov 2025	Accelerated	Hits 1-3: APRIL-targeting monoclonal antibody that blocks APRIL to modulate B-cells
Trutakna (atacicept)	Jul 2026	Accelerated	Hits 1-3: BAFF- and APRIL-targeting fusion protein that blocks both signals to modulate B-cells

*Full FDA approval is made based upon 2-year estimated glomerular filtration rate (eGFR) data in pivotal trials, while accelerated approval is based on 9-month urine protein-creatinine ratio (UPCR) data.

**Therapies are categorized by their predominant mechanisms of action, although many have secondary effects that may also contribute to clinical benefit.

NKF IgAN Workshops, Spring 2026

Together, NKF’s two spring 2026 scientific workshops addressed complementary challenges in the evolving IgAN treatment landscape: how emerging B-cell therapies should be used in clinical practice and how future clinical trials should be designed as treatment options and standards of care continue to expand.

The B-Cell Therapies for Treating IgAN Workshop convened nearly 50 leading nephrologists representing adult, pediatric, and transplant nephrology from across the United States to develop recommendations on the clinical use of B-cell therapies in IgAN. Discussions centered on three areas: patient selection, treatment monitoring, and combination therapy, all through the lenses of the adult, pediatric, and transplant patient populations.

The goal of this Workshop was to generate expert consensus recommendations on the clinical use of B-cell therapies in patients with IgAN. The group also identified research priorities needed to address lingering questions in the field. Expert consensus will be established through a structured Delphi process, which is currently ongoing, with a final report expected later this year. The resulting recommendations are intended to provide much-needed guidance in a rapidly evolving area of nephrology practice.

Beyond questions about the clinical use of B-cell therapies, the FDA approval of five treatments with several more in late-stage clinical development has also introduced important challenges for the design of future IgAN clinical trials. These include the declining patient interest in and feasibility of placebo-controlled studies, the growing need for active comparator arms, and the heterogeneous global standard of care in IgAN treatment. Additional barriers include patient eligibility criteria, rescue therapy thresholds, and trial duration, all of which limit companies' ability to recruit patients for clinical trials. Interestingly, these issues appear to be more prominent in the United States, for now.

To address these barriers, The Future of Clinical Trials in IgAN Workshop brought together nearly 100 attendees from around the world, including nephrologists, statisticians, patient organizations, regulators, and sponsors from 20 pharmaceutical companies. Discussions focused on advancing clinical trial design for IgA nephropathy in ways that are patient-centered, scientifically rigorous, and aligned with regulatory expectations. The planning committee is currently summarizing Workshop findings and intends to publish this guidance soon to help optimize trial design for the next generation of IgAN clinical trials.

Bringing Experts Together

IgAN is experiencing a remarkable period of progress, creating new possibilities for both patients and clinicians. At the same time, this pace of change has posed unique challenges in how best to integrate these emerging therapies into clinical practice and generate the evidence needed to guide the future evolution of IgAN care. Through these workshops, NKF is helping the field meet this moment by bringing experts together to address uncertainty, build consensus, and support the next phase of progress in IgAN.

**Information contained in this NKF educational resource is based on data available at the time of publication. It is intended to help clinicians stay informed about new scientific findings and developments. This resource is not intended to establish a preferred standard of care and should not be interpreted as prescribing an exclusive course of management.