Kidney Disease: Improving Global Outcomes (KDIGO) has issued comprehensive, evidence-based recommendations for clinicians managing immunoglobulin A nephropathy (IgAN) and immunoglobulin A vasculitis (IgAV). The new guideline, published in Kidney International, integrates evidence from randomized controlled trials through August 2024 and reflects the rapid pace of advances in glomerular disease research. The treatment landscape for IgA-driven kidney disease is changing quickly on the strength of new clinical findings.

“The new IgAN KDIGO guidelines are an important step forward in the care of individuals with IgA nephropathy,” said guideline co-author Brad H. Rovin, MD, professor of medicine and pathology, Lee A. Hebert Professor of Nephrology, and director at The Wexner Medical Center for Clinical Research Management in Columbus, Ohio. “In response to new data from registry studies looking at kidney failure due to IgAN, the guidelines suggest treatment should begin earlier than we have in the past, when proteinuria is at least 500 mg/d.”

IgAN is the most common primary glomerular disease and a leading cause of chronic kidney disease and kidney failure. IgAV, historically known as Henoch-Schönlein purpura, also carries significant risk for kidney damage, especially in children. A key advance in the guideline is the dual focus on both preventing or reducing IgA-containing immune complex (IgA-IC) formation and limiting IgA-IC injury, while treating complications of IgAN-related damage such as glomerular hyperfiltration and hypertension.

Setting New Standards for Proteinuria Levels

Treatment goals have been revised to a lower proteinuria level of ≤ 500 mg/d and to slow the decline in kidney function to ≤ 1 mL/min/1.73 m².

“Given the plethora of new therapies approved or in trial for IgAN, the revised guidelines provide a framework for integrating these treatments into daily care,” Rovin told Medscape Medical News. “Some of the newly approved therapies target the presumptive immunopathogenesis of IgAN, while others target the consequences of nephron loss due to IgAN.”

New recommendations include optimizing the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for all appropriate patients, using targeted-release budesonide (nefecon) in those at risk for progressive loss of kidney function, and employing newer agents such as sparsentan (a dual endothelin-angiotensin receptor antagonist) and SGLT2 inhibitors to mitigate IgAN-induced nephron loss. The guideline also provides direction for special situations, including IgAN with nephrotic syndrome, acute kidney injury, or rapidly progressive glomerulonephritis.

Most patients are expected to benefit from simultaneous treatment of immunologic drivers of nephron loss and therapies that slow progression due to prior nephron loss.

“This framework is critical because the changes in the IgAN treatment landscape have been profound and difficult to keep up with,” Rovin said. “The guidelines also allow us to efficiently add in new therapies to the treatment algorithm as they are approved.”

New Medications, New Paradigms

The update emphasizes preserving kidney function by intervening earlier and treating to lower proteinuria thresholds, approaches likely to significantly reduce progression to kidney failure. With newly approved options, slowing estimated glomerular filtration rate decline may directly improve kidney survival.

“The guidelines attempt to put the IgAN therapeutic landscape into perspective and provide a rationale of what could be used and where it acts in the IgAN pathway,” Rovin said. “Because trials and new treatments have come so rapidly to the nephrology community, there has been considerable confusion about the new drugs, and when and how to use them.”

The guideline includes additional advice for pregnancy planning and pediatric management. It also highlights treatment disparities. Many regions with the highest prevalence of IgAN, such as Asia, remain underrepresented in trials and face barriers to accessing newly approved therapies. KDIGO emphasizes the need for equity so that advances benefit all patients, not just those in resource-rich settings.

“These guidelines are important to standardize care globally and are inclusive of all ages, with specific mention of children,” said Louise Oni, MBChB, MRCPCH, MA, PhD, senior lecturer in pediatric nephrology at the University of Liverpool in Liverpool, England. “They can be adapted for country-specific implementation to make them suitable for their local environment.”

Treatment Landscape Changing Quickly

KDIGO previously published its first guideline devoted to hepatitis C and chronic kidney disease in 2008, with several others since, including a broad glomerular diseases guideline in 2021.

Recognizing the rapid pace of discovery in IgA-related disease, KDIGO plans ongoing updates to the new guideline as data and approvals evolve. Under the new framework, these conditions are no longer managed with a single approach but with a toolkit of therapies.

“The treatment landscape for IgA-related glomerulonephritis is transforming,” Oni told Medscape Medical News. “There remains a delay in getting evidence for children; however, there is now a global effort to accelerate this progress so we can champion an equitable specialty.”

Kartik Kalra, MD, clinical associate and the nephrology fellowship co-director at the Geisinger Medical Center in Danville, Pennsylvania, called the new guideline a pivotal advance.

“By integrating the latest data from multiple randomized trials and emphasizing a dual therapeutic strategy, targeting both immune complex formation (disease modification) and maladaptive responses of the kidney to nephron loss (foundational therapies), the guideline empowers physicians to personalize care and intervene earlier,” he told Medscape Medical News.

Kalra added that with novel agents such as targeted-release budesonide, sparsentan, and SGLT2 inhibitors, the field is shifting from traditional approaches to a dynamic, multi-modal paradigm targeting disease pathogenesis.

“This update is not just timely, it’s essential for improving outcomes and equity in kidney care worldwide,” Kalra said. “I’m eager to see more long-term clinical trial data in IgA nephropathy, especially those focusing on disease modification. Advancements in targeted therapies could significantly improve outcomes for patients with progressive forms of the disease.”

The guidelines listed the financial disclosures for each member of the panel. Oni and Kalra reported no financial disclosures.

John Schieszer, MA, is an award-winning national journalist and podcast broadcaster of The Medical Minute. He can be reached at medicalminutes@gmail.com.