Opportunities in IgA Nephropathy Research: Exploring the 4 Hit Process

May 12, 2025 at 01:00 AM EDT

SPONSORED CONTENT -- (StatePoint) IgA nephropathy is a progressive, autoimmune, chronic disease that predominantly affects adults between the ages of 20 and 40, with an annual global incidence of 2.5 cases per 100,000 people. Despite its prevalence, IgA nephropathy remains a challenging disease to manage and treat.

The condition is characterized by the accumulation of immune complexes containing Gd-IgA1 in the kidneys. Over time, IgA nephropathy leads to kidney injury and can progress to kidney failure, requiring dialysis and/or kidney transplantation.

Recognizing the Patient Burden

The disease may present as asymptomatic in its early stages, but manifests in various ways, including hematuria (blood in the urine) or proteinuria (protein in the urine). Symptoms may include fatigue, backache, high blood pressure, and foamy or tea-colored urine, among others.

The impact of IgA nephropathy extends beyond the physical health of patients. As the disease progresses, patients may experience increased anxiety, impairment in daily activities, and reduced work capacity. Dr. Edgar Lerma, a leading nephrologist, explains, “Proper identification and diagnosis of IgA nephropathy are crucial, especially as patients are typically diagnosed in their 20s to 40s. Unfortunately, many will eventually progress to end-stage kidney disease, adding a physical and emotional strain not only on patients, but also on their families.”

The road to diagnosis can often be delayed, as symptoms may initially be subtle or not identified. This can lead to a delayed treatment response, further complicating disease management. As patients face progressive kidney dysfunction, identifying an effective care plan with their healthcare provider is essential.

Understanding the Treatment Landscape

Treatments may help manage symptoms and slow disease progression. Optimized supportive care today focuses on blood pressure control, renin-angiotensin system inhibition, and lifestyle modifications. In higher-risk patients, immunosuppressive therapies may be used, though they may come with significant side effects and long-term toxicity.

Despite the availability of these treatments, Dr. Lerma emphasizes, “Continued research into IgA nephropathy remains crucial to uncovering new opportunities and advancements in our understanding and treatment of patients.”

The Role of APRIL and the 4 Hit Process in IgA Nephropathy

One area of opportunity in IgA nephropathy research is the role of APRIL (A PRoliferation-Inducing Ligand), a cytokine in the tumor necrosis factor (TNF) family, and a key driver of the 4 hit process, which is an important initiating and sustaining factor in IgA nephropathy pathogenesis.

As Dr. Lerma explains, “Targeting APRIL and the 4 hit process represents a potential therapeutic strategy to disrupt IgA nephropathy’s pathogenesis. This is the process in which pathogenic Gd-IgA1 is produced, leading to the synthesis of autoantibodies against Gd-IgA1, immune complex formation, and deposition in the glomerular mesangium, which may lead to kidney injury and can progress to kidney failure.”

Pioneering Research to Transform the Future of Kidney Care

Otsuka Pharmaceutical Development & Commercialization, Inc. is committed to developing and advancing innovative treatments for kidney diseases, including IgA nephropathy. These efforts include clinical research and commercialization of new treatments, patient education and support initiatives to enhance the overall care and management of nephrological conditions.

“Our commitment to nephrology is driven by a deep sense of responsibility to patients facing complex kidney diseases. Through relentless innovation and research, we strive to develop advanced treatments that address high unmet needs, including IgA nephropathy,” says Lina Floren Smith, vice president of nephrology and immunology business at Otsuka. “Beyond treatment, we are dedicated to supporting patients through education and initiatives that enhance overall care, seeking to ensure that they receive the best possible outcomes.”

To stay informed about IgA nephropathy, including the role of APRIL and the latest research advancements, consider signing up for updates at www.discoveraprilinigan.com.

February 2025 21US25EUC0005

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Photo Credit: (c) sasirin pamai / Shuttershock

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Opportunities in IgA Nephropathy Research: Exploring the 4 Hit Process

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