If you or someone you love has IgA nephropathy (IgAN), you may wonder why it developed in the first place. The answer is not always simple. Researchers still don’t know exactly what causes IgAN, and the reasons it develops may differ from person to person.

Scientists have identified several possible triggers and risk factors that may play a role, including genetics, immune system changes, infections, and other health conditions. Understanding what researchers know so far can help you make more sense of why IgAN develops and what may influence it.

How IgA Nephropathy Affects the Kidneys

The kidneys are the body’s natural filters. Each kidney has about a million tiny filters called glomeruli. These filters clean the blood by removing waste and sending it out of the body through urine.

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In IgAN, IgA proteins get trapped in the glomeruli. This buildup triggers inflammation, which is the body’s way of trying to heal itself. But, in this case, the immune system reaction causes more harm than good. The ongoing inflammation scars the filters, making it harder for the kidneys to do their job.

At first, many people don’t notice symptoms. Over time, though, IgAN can cause blood or protein in the urine, swelling in the hands or feet, and high blood pressure. In severe cases, it can also lead to complications like chronic kidney disease (CKD) or even kidney failure.

Possible Triggers and Risk Factors

Health experts aren’t sure exactly what causes IgAN, but research suggests several biological, genetic, and environmental influences may be involved in causing the glomerular disease. Here are seven possible triggers and risk factors linked to IgAN.

One of the strongest clues about why IgAN develops is family history. Studies show that certain diseases can run in families, which suggests a genetic link.

This means that having a close relative with IgAN may raise your risk. About 10 percent of people affected by IgAN have a family history of the disease. However, some people who carry related genes never develop symptoms.

How Genes May Contribute to IgAN

Scientists have found certain genes that seem to play a role in how the immune system makes and clears IgA. Changes in these genes may cause the body to make abnormal IgA. This IgA is more likely to stick to the kidneys.

A study published in the Journal of the American Society of Nephrology found that genes linked to the immune system and inflammation may affect who develops the disease. These genes may also play a role in how severe the condition becomes.

Even though genes can raise the risk, they don’t cause IgAN on their own. Most scientists believe genes interact with infections or changes in the immune system to trigger the disease.

Since IgAN is related to the immune system, many scientists believe it’s caused by immune system overactivity. Normally, IgA antibodies help fight bacteria and viruses, especially in the mouth, lungs, and intestines. In IgAN, the immune system may make too much IgA or a form of IgA that clumps together and gets stuck in the kidneys.

Researchers think this may happen because the immune system produces antibodies that bind to an abnormal form of IgA. These antibody-IgA clumps can build up in the kidneys and can cause inflammation that leads to scarring over time.

One study found that certain immune cells — B cells and plasma cells — may make an abnormal form of IgA with missing sugar molecules. This abnormal IgA can clump together and trigger inflammation that damages the kidneys.

Many people first develop symptoms of IgAN after an infection. Respiratory infections that affect the nose, throat, or lungs and infections that impact the digestive tract have been identified as specific culprits. This suggests that some infections may trigger IgAN or make it worse.

When you get sick, your body makes more IgA to fight germs. In people with IgAN, this response may be overactive. Colds, the flu, or tonsillitis can then trigger flare-ups or worsen symptoms. This may also happen due to changes in gut bacteria.

This doesn’t mean infections cause IgAN. Instead, they may trigger symptoms or make an underlying immune problem worse.

Certain health conditions also seem to increase the risk of developing IgAN or make it worse. These include:

• Liver disease — When the liver is damaged, it may not clear IgA from the blood properly, leading to higher levels that can build up in the kidneys.
• Celiac disease — People with celiac disease, an autoimmune disease triggered by gluten, may have higher IgA levels and a greater risk of kidney inflammation.
• Inflammatory bowel disease (IBD) — Conditions like Crohn’s disease and ulcerative colitis also affect the immune system and gut, where much of the body’s IgA is made.
• Viral infections — Infections caused by viruses, such as HIV, hepatitis B, and coronavirus (COVID-19), can send the immune system into overdrive, causing it to make too many IgA antibodies that can then collect in the kidneys and cause damage.
• IgA vasculitis — Sometimes called Henoch-Schönlein purpura, this condition also causes IgA antibodies to collect where they shouldn’t, specifically in the tiny blood vessels of organs.

Researchers continue to study how these diseases may be connected to IgAN. These conditions may lead to abnormal IgA or increase the risk of kidney damage.

Genes and the immune system appear to play key roles in how IgAN develops. But, some environmental and lifestyle factors seem to affect how severe the disease becomes and how quickly it worsens. These include:

• Smoking — Smoking can worsen kidney damage and raise blood pressure, both of which make IgAN progress faster.
• Hypertension (high blood pressure) — Long-term high blood pressure adds stress to the kidneys and can speed up loss of kidney function.
• Diet and lifestyle — Diets high in salt may worsen blood pressure issues, which affect overall kidney health.

These factors don’t cause IgAN directly, but they can make it harder for the kidneys to stay healthy once the condition develops.

Medications Linked to IgAN

Some cancer and immune medications have been shown to trigger IgAN. Medications that have been linked to IgAN include:

• Immune checkpoint inhibitors
• Tumor necrosis factor-alpha inhibitors
• Warfarin
• Direct oral anticoagulants
• Antithyroid medications, such as those used to treat Graves disease

According to Mayo Clinic, IgAN can affect anyone, but the condition does appear to be more common in men than women. It also tends to affect white and Asian people more often than Black people.

So far, researchers have only observed these differences. They don’t yet know the exact reason why risk varies by gender and ethnicity.

Although scientists have identified many risk factors, the exact cause of IgAN is still not fully understood. The disease may be caused by a combination of genetic, immune, and environmental factors coming together at the right time.

This means that although you can’t always prevent IgAN, you can take steps to protect your kidneys once you know you have it. Regular checkups, blood pressure control, not smoking, and following your healthcare provider’s advice about medications and diet can all help slow disease progression.

Living With IgA Nephropathy

If you or someone you love has IgAN, it’s natural to feel uncertain or worried about the future. Remember that everyone’s experience is different. Some people live for many years with mild symptoms, while others may need more regular monitoring or treatment.

Working closely with your nephrologist (kidney specialist), staying on top of lab tests, and making healthy lifestyle choices can make a big difference. Managing blood pressure, avoiding medications that can harm the kidneys, and eating a balanced, low-salt diet are all helpful steps.

Join the Conversation

On myIgANteam, people share their experiences with IgA nephropathy, get advice, and find support from others who understand.

What has helped you the most in managing your kidney health? Let others know in the comments below.