Understanding how IgAN
may fall into place
How IgAN (IgA nephropathy) starts and progresses.
Your kidneys work around the clock to keep your body in balance. They filter out waste, remove excess fluid, and help keep important minerals balanced in your blood.
Inside each kidney are about a million tiny filtering units called nephrons. Nephrons contain an even smaller structure known as a glomerulus. The glomerulus acts like a strainer inside each nephron. This allows your body to remove toxins while keeping the nutrients it needs.
In people with IgAN, your immune system can trigger a harmful chain reaction that can cause damage to your nephrons and glomeruli over time. This is why IgAN is considered a progressive, chronic, autoimmune kidney disease. It actually starts outside your kidneys in your immune system.
When the kidneys
are damaged, they
can’t filter properly,
which can lead to issues like:
Proteinuria
Foamy urine from too much protein leaking into your urine
Hematuria
Blood in urine can be invisible or make it pink or cola-colored
The role of your immune system
and the 4-hit
process in IgAN
The immune system helps protect the body by identifying and reacting to harmful invaders by making antibodies. Antibodies help your body fight infections. In IgAN, your body produces an abnormal antibody that your immune system identifies as a threat. This can trigger a repetitive sequence of events that happen over 4 steps.
This is known as the 4-hit process, and it can lead to irreversible kidney damage. Over time, this damage can weaken kidney function and lead to kidney failure, which may lead to dialysis or a kidney transplant.
The diagram below shows the 4-hit process in more detail.
The 4-hit process is the chain reaction driving IgAN
Hit 1
Production of abnormal IgA
Your immune system makes IgA, a type of antibody. In IgAN, your body produces an abnormal antibody called Gd-IgA1.
Hit 2
Targeting abnormal IgA
Your immune system mistakes this abnormal antibody as a threat and attacks it by forming autoantibodies.
Hit 3
Forming of clusters
The autoantibodies bind to the abnormal antibodies and cause large clusters, called immune complexes, to form.
Hit 4
Kidney damage
These large clusters move through the bloodstream to the kidneys and disrupt how they work. This can lead to inflammation and scarring (fibrosis) in the kidneys and a decline in kidney function.
The importance of APRIL
and its role in the 4-hit process
Cytokines help your immune system communicate with the rest of your body. One cytokine, APRIL (A Proliferation-Inducing Ligand), is an immune messenger that helps your body make certain types of antibodies, like IgA. But in IgAN, this cytokine also causes your body to make an abnormal type of IgA antibody called Gd-IgA1. Because it signals the immune system to keep making abnormal IgA antibodies, APRIL is one of the main drivers of the harmful chain reaction that can lead to irreversible kidney damage.
Learn more
about the 4-hit
process and what
drives IgAN
Learn more
about the 4-hit
process and what
drives IgAN
Some important things to know about IgAN
IgAN
can start
silently
Many people may not recognize symptoms in the early stages
It is a
progressive
kidney disease
Even if you don’t have symptoms, IgAN can weaken kidney function over time, and cause irreversible damage to your kidneys
Researchers
are studying
its root causes
We know IgAN begins with
your immune system
Diagnosing IgAN
is the next step
in your journey
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National Institute of Diabetes and Digestive and Kidney Diseases. IgA nephropathy. National Institute of Diabetes and Digestive and Kidney Diseases. Updated April 2021. Accessed April 11, 2025.
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Cheung CK, Barratt J, Lafayette R, et al. Targeting APRIL in the treatment of glomerular diseases. Kidney Int. Published online 2024.
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Mayo Clinic Staff. IgA nephropathy. Mayo Clinic. Published August 10, 2022. Accessed April 11, 2025.
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Selvaskandan H, Shi S, Twaij S, Cheung CK, Barratt J. Monitoring immune responses in IgA nephropathy: biomarkers to guide management. Front Immunol. 2020;11:572754.
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Cleveland Clinic. Cytokines. Cleveland Clinic. Published August 10, 2023. Accessed April 11, 2025.
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Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S1–S150.
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