WHAT CAUSES IGA NEPHROPATHY (BERGER'S DISEASE)?

Immunoglobulin A nephropathy (also known as IgA nephropathy or Berger's disease) is an autoimmune disease that affects the kidneys. It develops when too much of the protein IgA builds up in the kidneys, damaging the organ's network that filters waste and fluids from the blood.

It's not entirely clear what causes IgA nephropathy to develop, but research suggests that genetics and environmental factors can influence the condition to develop.

Theories

IgA nephropathy occurs when there are extra deposits of the IgA antibody in the kidneys. These antibodies are a type of protein that the immune system uses to protect against infection. If your body produces too many of these antibodies, they can get stuck in the kidneys and accumulate. This eventually damages the organs.

Researchers don't know exactly why this happens, but they have proposed a few theories: genetics and environmental triggers.

Genetics

There appears to be a genetic component to having IgA nephropathy. Studies suggest that your chances of developing IgA nephropathy increase if you have a family history of the disease.

That said, it doesn't always mean you will end up with the condition just because you inherited a gene linked to IgA nephropathy. Experts believe that a combination of genetic and environmental factors contribute to IgA nephropathy's development.

Environmental Triggers

In addition to having a genetic predisposition for developing IgA nephropathy, environmental factors that affect the immune system may trigger this condition. These factors can vary by person, so not all triggers will affect everyone similarly.

A primary environmental trigger for IgA nephropathy is a recent upper respiratory infection (URI), cold, or sore throat. In many cases, this appears to prompt the development of IgA nephropathy.

Experts think that when these infections start brewing, the IgA immune proteins start circulating throughout the body before reaching the kidneys.

Stress, another commonly understood risk factor for kidney disease, may also contribute to the development of IGA nephropathy. The body's stress response can increase inflammation, interfering with the kidneys' blood-filtering function.

Is It Hereditary?

For some people, IgA nephropathy can be passed down in families. Research has uncovered certain genetic mutations (or changes) that likely play a role in the development of IgA nephropathy.

So far, at least 18 different genetic variants linked to the condition have been identified, including C1GALT1 and C1GALT1C1, which have also been linked to the development of other cancers.

However, it's estimated that around 10% of cases or less are due to familial (hereditary) IgA nephropathy. This suggests that most cases may actually develop in people without a known family history of the condition.

Who Gets It?

IgA nephropathy is one of the most common causes of chronic kidney disease, alongside high blood pressure and diabetes. Roughly 1 in 10 kidney biopsies in the United States indicate IgA nephropathy.

In the U.S., some people are more likely to develop the condition than others. Factors include the following:.

  • Age: IgA nephropathy can develop at any age, but it's more common in people ages 10-40.
  • Sex: People who were assigned male at birth are twice as likely to develop IgA nephropathy than people who were assigned female.
  • Ethnicity: IgA nephropathy is seen more often in people with white European and East Asian ancestry than it is in people of Black descent. However, more data for all ethnic backgrounds is needed.

Risk Factors

Like other autoimmune diseases, there isn't much specific evidence around why this condition develops in the first place. A combination of genetics, environmental triggers, and circumstances like infections, stress, and lifestyle factors seem to influence the onset and severity of Berger's disease.

Geography

The prevalence of IgA nephropathy varies by global geographic region. For example, evidence shows this condition is present in 40% of kidney biopsies done in Asia, compared to 20% in Europe and 10% in North America.

Other research suggests that this disease seems to be more common in geographic areas with a warm, humid climate, where there's a higher risk of certain infections (like urinary tract, viral, or gastrointestinal infections).  However, additional data is needed to solidify these findings.

Health Conditions

Although it's not clear what actually causes the IgA protein to build up in the kidneys, the following health conditions are strongly linked to developing Berger's disease:

  • Liver diseases: Common liver conditions like cirrhosis (liver scarring) and hepatitis B or C infections (liver inflammation) are connected to Berger's disease. A few more rare liver disorders, including hemochromatosis, Wilson disease, and autoimmune hepatitis, likely also have a link to this condition.
  • Celiac disease: This condition is triggered when the immune system reacts to eating gluten, a protein found in most grains. People with celiac disease are at a higher risk of developing IgA nephropathy.
  • Infections: Human immunodeficiency virus (HIV), certain viral and bacterial infections, and upper respiratory tract infections (URIs) are strongly linked to the development of Berger's disease.
  • Other autoimmune disorders: IgA nephropathy has also been associated with other conditions that affect the immune system, such as Sjögren's syndrome, spondyloarthritis, systemic lupus erythematosus (lupus), and Behçet disease.
  • Digestive disorders: Inflammatory bowel disease (IBD)—either Crohn's disease or ulcerative colitis—is another risk factor for developing IgA nephropathy.

Research suggests that several other health conditions may have some connection to this kidney disease, too:

  • Skin conditions: Psoriasis is the skin condition most often linked to IgA nephropathy.
  • Gut dysbiosis: People with IgA nephropathy often have abnormal intestinal microbiota, an imbalance in the bacteria in the gut. Specifically, evidence suggests a lack of healthy bacteria diversity with the Clostridium, Enterococcus, and Lactobacillus strains compared to people who don't have the condition.

Lifestyle Habits

However, underlying health conditions, genetics, and environmental factors aren't the only things that can raise your risk of Berger's disease. Your lifestyle habits may also play a role.

Research suggests that smoking or being exposed to secondhand smoke increases your risk of developing kidney disease. Experts think this habit could worsen the development—and progression—of IgA nephropathy because of the way that tobacco smoke damages the blood vessels in the body. Limiting exposure to secondhand smoke and avoiding or quitting smoking can help lower your risk.

Medications

Less commonly, taking certain medications can sometimes increase your risk of Berger's disease. Some of these medications can affect the immune system function and influence IgA antibodies to develop, including:

  • Vancocin (vancomycin): Treats bacterial infections like Clostridioles difficile (C. diff)
  • Rocephin (ceftriaxone): Antibiotic that treats different bacterial infections
  • Tegretol (carbamazepine): Help stop seizures
  • Gengraf (cyclosporine): Suppresses an overactive immune response and is sometimes used to treat certain skin conditions (like psoriasis)

A Quick Review

IgA nephropathy (Berger's disease) is a condition that develops when IgA antibodies build up in the kidneys as part of an immune system reaction—leading to eventual kidney damage.

The exact cause of IgA nephropathy is unknown, but research suggests that it results from a combination of genetic and environmental triggers. Factors like a family history of the disease, male gender, white or Asian ancestry, smoking, and having certain underlying conditions can increase your risk of developing this disease.

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2024-09-30T16:14:50Z dg43tfdfdgfd