How does immunoglobulin a nephropathy damage the kidneys?

Immunoglobulin A nephropathy (IgAN) is a form of kidney disease. While less common than many other types of kidney disease, IgAN is a leading cause of a type of kidney damage called glomerulonephritis.

What is glomerulonephritis?

The kidneys act as filters for the blood. Each kidney contains about a million filtering units called nephrons. As blood flows into one of these filtering units, it passes through a network of tiny blood vessels called a glomerulus. The plural of glomerulus is glomeruli.

These blood vessels are covered in a barrier that allows some substances to pass through the blood vessel walls while keeping other substances in the bloodstream. As blood moves through a glomerulus, excess fluid, salts, and cellular waste are filtered out and become urine. Substances like proteins and blood cells remain in the bloodstream.

Glomerulonephritis is inflammation of the glomeruli. Inflammation is one of the main ways that the body’s immune system responds to an irritant, such as a germ, injury, or a foreign object like a splinter.

How does IgAN cause glomerulonephritis?

In very basic terms, IgAN causes clogs inside the blood vessels of the glomeruli. These clogs act as an irritant that triggers an inflammatory response by the immune system. The glomeruli become inflamed as the immune system attempts to clear away the clog.

This is a complex, multi-step process:

• Immunoglobulin A is a protein that prevents germs and other harmful substances from entering cells. It is mostly found in the respiratory system and digestive tract. When a person has IgAN, the body produces abnormal immunoglobulin A.
• The immune system produces antibodies to try to get rid of the abnormal immunoglobulin A.
• Antibodies attach to immunoglobulin A, creating an immune complex. Normally, an immune complex is something that immune cells can consume or destroy. With IgAN, antibodies and abnormal immunoglobulin A form larger complexes that become stuck in the blood vessels of the glomeruli.
• The immune system responds and attempts to clear this clog. Part of this response involves the release of substances that cause inflammation.

Inflammation causes damage and sometimes scarring. As inflammation continues and damage accumulates, the kidneys lose function and become less effective at filtering the blood.

As a result, protein and blood can leak into the urine, and excess fluid and cellular waste can remain in the bloodstream. Blood pressure can become chronically elevated (hypertension), contributing to further damage to the kidneys and complications like heart failure.

In some cases, IgAN leads to end-stage renal disease, or kidney failure. At this stage, the kidneys no longer function well enough to keep a person alive, and the only treatment options are dialysis and/or kidney transplant.

How is IgAN treated?

There is no cure for IgAN, and treatment focuses on protecting kidney function and preventing complications.

Treatment recommendations will depend on several factors, including any associated conditions or potential secondary causes. The majority of cases of IgAN occur without any identifiable cause. This is known as primary IgAN.

Treatment for primary IgAN can include medications to control blood pressure and reduce proteinuria (protein in the urine). It may also include medications to treat edema (swelling due to fluid buildup), control inflammation, and lower cholesterol levels.

A smaller percentage of cases are associated with an existing health condition or the use of certain medications. This is known as secondary IgAN. With secondary IgAN, treatment focuses on addressing the underlying cause.

Treatment often includes changes to diet and lifestyle, such as limiting the intake of sodium, proteins, and fats, as well as quitting smoking (for anyone who smokes). A healthcare provider will always be your best source of information, and can recommend guidelines based on your diagnosis, overall health, and test results.