Primary IgA nephropathy is a common primary disease of the kidney filters. It’s considered a primary glomerular disease, meaning the kidney problem is not caused by another health condition.

In primary IgAN, abnormal IgA proteins form in the body and build up in the kidneys, where they can damage the glomeruli.

How It Develops

Doctors often explain primary IgAN using what’s called the “four-hit” model. In this model, a “hit” is one step in a chain of changes that can lead to kidney damage. Each step builds on the one before it.

The four hits are:

• First hit — The body makes too much galactose-deficient IgA1. This form of IgA1 has less galactose, a type of sugar, and is thought to be produced mainly in the gut and lining of the nose.
• Second hit — The immune system creates autoantibodies (antibodies that mistakenly target something from your own body). These target the altered IgA1.
• Third hit — The antibodies attach to the altered IgA1 to form immune complexes in the bloodstream.
• Fourth hit — The antibody complexes settle in the kidney filters. This triggers inflammation and prompts cells there to release cytokines — immune-system signals that can injure the glomeruli.

Signs and Symptoms of Primary IgAN

Many people with IgAN feel healthy for years. Early changes may only be found during routine tests that show blood or protein in the urine.

When IgAN symptoms do appear, they may include:

• Dark or tea-colored urine, sometimes after a cold or infection
• Foamy urine due to protein loss
• Swelling in the hands, feet, or face
• Flank pain (back or side pain)
• High blood pressure
• Fatigue (unusual tiredness or weakness)

Diagnosis and Monitoring

Primary IgAN is confirmed with a kidney biopsy. A small tissue sample is checked with special dyes that make IgA deposits visible under a microscope.

Doctors may also monitor kidney health with:

• Serum creatinine (a blood test that reflects kidney function)
• Glomerular filtration rate (GFR), which measures how well the kidneys filter waste
• Urinalysis (urine test) to check for blood and protein

Treating Primary IgA Nephropathy

Treatment for IgA nephropathy focuses on protecting the kidneys and reducing inflammation. Many medications are used to treat IgA nephropathy, but not all are specifically approved by the U.S. Food and Drug Administration (FDA) for the disease.

Angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers can lower blood pressure and reduce protein in the urine. They’re often a first choice for treatment even though they’re not FDA-approved specifically for IgA nephropathy.

Current FDA-approved therapies for adults with primary IgA nephropathy include:

• Budesonide (Tarpeyo) — This corticosteroid calms the immune system. Its targeted-release formula acts in the part of the intestine involved in producing abnormal IgA.
• Sparsentan (Filspari) and atrasentan (Vanrafia) — These medicines block endothelin receptors and can lower the amount of protein in your urine.
• Iptacopan (Fabhalta) — This complement inhibitor targets part of the immune system to reduce kidney inflammation.
• Sibeprenlimab (Voyxact) and atacicept (Trutakna) — These medicines block APRIL, BAFF, or both, immune signals involved in making abnormal IgA.

Other medications, such as SGLT2 inhibitors, are FDA-approved for chronic kidney disease (CKD) rather than IgAN specifically.

Unlike primary IgAN, secondary IgAN occurs when IgA nephropathy is linked to a separate condition. These related conditions may affect how IgA is produced, processed, or cleared.

What Triggers Secondary IgAN?

A number of underlying conditions have been linked to secondary IgAN. The exact way they contribute to IgA deposits may differ from one condition to another. Some of the most common triggers include:

• Liver disease, especially cirrhosis (liver scarring)
• Inflammatory bowel diseases, such as Crohn’s disease or ulcerative colitis
• Chronic (ongoing) bacterial or viral infections
• Immune-related diseases, such as lupus, psoriasis, or celiac disease
• Certain blood cancers or immune disorders

Symptoms, Diagnosis, and Treatment of Secondary IgAN

Secondary IgAN often looks similar to primary IgAN. Signs may include blood or protein in the urine, swelling, and rising blood pressure. It occurs alongside an underlying condition, such as liver disease.

A kidney biopsy can confirm IgA deposits, and doctors may also look for clues that another illness is contributing to the kidney disease.

Treatment usually focuses on the underlying disease, along with supportive measures to protect the kidneys. The best approach depends on what condition is contributing to the IgA deposits.

Managing cirrhosis, treating a chronic infection, or controlling autoimmune disease may improve kidney findings if that condition is contributing to IgA deposits. Some cases improve significantly once the trigger is addressed.

While not a formal type of IgAN, IgA-associated nephropathy is a term used to refer to related conditions in which IgA affects both the kidneys and other organs. The most well-known example is IgA vasculitis, formerly called Henoch-Schönlein purpura. In this condition, IgA deposits collect not only in the glomeruli but also in small blood vessels throughout the body.

How It Develops

In IgA vasculitis, IgA deposits can collect in the kidneys and the blood vessel walls of the skin, digestive tract, and joints. Unlike primary IgAN, IgA-associated nephropathy begins as a systemic (whole-body) condition.

Because the condition affects more than the kidneys, symptoms outside the kidneys may appear before or around the same time as urine changes. Many children recover fully, while adults are more likely to develop lasting kidney problems.

Signs and Symptoms of IgA-Associated Nephropathy

Because IgA-associated nephropathy can affect several body systems at once, symptoms may differ from those of primary and secondary IgAN. Common symptoms may include:

• Purpura (a raised rash that may be red or purple and can look like a bruise, depending on skin color) on the legs, feet, or buttocks
• Swollen, painful joints
• Abdominal (belly) pain, nausea, or vomiting
• Dark or bloody stools
• Blood or protein in the urine

Diagnosis and Treatment

IgA-associated nephropathy may be diagnosed based on its rash along with joint and digestive symptoms. Blood and urine tests can help rule out other illnesses and show whether the kidneys are working properly. Sometimes, a skin biopsy is done to look for IgA deposits.

If kidney problems are more serious, a kidney biopsy may be needed.

In children, most cases of uncomplicated IgA vasculitis improve on their own with rest and fluids. Adults have a greater risk of lasting kidney problems and may need ongoing monitoring.

For pain control, healthcare providers may recommend acetaminophen. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen can harm the kidneys when used at high doses or for a long time. If you have kidney problems, ask your healthcare provider whether an NSAID is safe for you.

If abdominal or joint pain is severe, corticosteroids may help reduce pain and swelling. Rare complications, such as bowel blockage, may require surgery.