How IgA Nephropathy Is Treated: A Look at Today’s Medications and Tomorrow’s Breakthroughs
Leading researchers and experts in rare kidney diseases first seek to gain insight into the causes of the disease and its progression before figuring out how to target the triggers of disease with new therapies. Extensive research has been conducted to understand the development pathway of IgA Nephropathy (IgAN), a chronic, rare, and progressive disease. These findings continue to drive the creation of new & novel treatments.
What causes IgAN?
To understand what causes IgAN, there needs to be an understanding of how the kidney works. Blood flows throughout the body and into the kidneys, where waste is filtered from the blood and converted into urine to be eliminated.
IgAN is triggered when a person’s body makes a kind of protein that the immune system thinks is problematic and mistakenly attacks it. The immune system creates IgA1, a type of antibody, which travels through the blood looking for the protein. When it finds it, it binds to the protein it has mistaken as an enemy, causing it to clump together. These clumps get trapped in the kidney filters, known as glomeruli. This results in swelling and inflammation, which damages the filters. Over time, this damage can worsen, impacting kidney function.
How do you treat IgAN?
Treating IgAN is complicated, because of the many different systems in the body that are affected. For instance, the immune system’s overreaction and production of damaging antibodies not only causes clumps to form, but also causes inflammation which can further affect the function of the kidneys. Targets for treatment, therefore, may focus on immunosuppressants, which impact the immune system, or include treatments that target the complement system, the source of the inflammation.
The choice of how to treat IgAN needs to be specific to the individual, with the doctor deciding which approach or if a combination of approaches would work best for each patient.
It is still a challenge for doctors to identify which of their patients with IgAN are more likely to progress, because there is no specific sign or element that increases with more disease activity. Instead, doctors must use clinical tests of blood and urine to find signs of damage or disease, such as the amount of protein (proteinuria) or persistent blood (hematuria) in urine, or the amount of waste products in the blood (high levels of eGFR).
Since IgA Nephropathy is a kidney disease that can worsen over time, doctors use different medicines to help protect the kidneys and slow the disease. Here's a simple guide to some of the main treatments:
New therapies in development
New research on several different types of therapy is underway. Disease-specific treatment options are being studied, exploring the source of the disease-causing pathways and finding ways to work on those pathways to stop disease progression.
Since IgA Nephropathy is an autoimmune disease, and the damage to the kidneys is caused by the production of autoantibodies, some new therapies seek to stop the production of these autoantibodies, or prevent them from triggering inflammatory responses that cause progression and further damage.
Removing certain cells that make harmful proteins and autoantibodies over time should lead to fewer harmful immune reactions, which will help protect the kidneys and keep them working better for longer.
The recommendation for people with IgA Nephropathy starts with healthy habits, such as quitting smoking, eating less salt and protein, keeping a healthy weight, and exercising.
It's also important to keep blood pressure under control and lower the amount of protein in the urine using RAAS inhibitors. The first step for treating most people with IgA Nephropathy is to follow this supportive care plan for at least 3 months. This 3-month countdown starts once the person’s blood pressure is at the right level. If immunotherapy is being considered, it would be given after 3 months, for 6-9 months.
IgAN is a long-term illness that can come and go, so doctors need to keep checking on it even after treatment starts. Some strong medicines (like steroids or other special drugs) can help for a while, but their effects often fade after stopping them. Because of this, some people may need more than one round of treatment or stay on medicine longer to keep the disease under control.
Doctors have studied many signs to figure out which patients might get worse over time. One important sign is how much protein is in the urine when the disease is first found. If there is only a small amount (less than 1 gram per day), the disease usually gets worse slowly. But if there is a lot of protein (more than 3 to 3.5 grams per day), the disease can get worse faster.
If the amount of protein in the urine goes down, the kidneys usually do better.
That’s why it’s really important to try to lower the protein in the urine to less than 1 gram per day.
Conclusion
The biggest challenges in treating IgA Nephropathy are figuring out how active the disease is, how much damage has already been done, and how likely it is that the kidney function will get worse. After that, treatment should be chosen based on what each patient needs most. Scientists are still studying special treatments for this disease, and early results look hopeful.
Source: Karoui KE, Fernando FC, De Vriese AS. Treatment of IgA Nephropathy: A Rapidly Evolving Field, J Am Soc Nephrol 2023; 35(1):103–116.
