Key points to consider
- C3G and IgAN are kidney diseases in which the abnormal accumulation of proteins in the kidney’s filtering units causes inflammation and damage, ultimately impairing kidney function.
- Treatment for these conditions focuses on controlling inflammation and reducing kidney damage using medications such as ACE inhibitors, ARBs, steroids, immunosuppressants, and complement inhibitors.
- While there is currently no cure, early and ongoing action can help slow the progression of kidney damage. It may include advanced therapies such as dialysis or, in some cases, transplantation.
Complement 3 glomerulopathy (C3G) and immunoglobulin A nephrosis (IgAN) are rare appearances of chronic kidney disease (CKD). These are glomerular diseases, which means that they originate from processes that affect the glomeruli, the filtration structures of the kidneys.
In both C3G and IgAN, the buildup of substances in the glomeruli causes inflammation and damage, limiting the kidneys’ ability to filter blood.
Over time, such inflammation and resulting damage lead to CKD and associated health problems. Both C3G and IgAN are treatable, and early treatment can help preserve kidney function.
Overview of treatments for C3G and IgAN
C3G and IgAN are caused by different types of accumulation in the kidney glomeruli.
C3G results from the accumulation of the C3 protein, a protein produced by the body’s complement system (also known as the “complement cascade response”).
The complement system contributes to immune system function in various ways. When this system becomes dysregulated (altered), as occurs in C3G, the C3 protein accumulates in the glomeruli, causing kidney damage.
Immune system dysfunction also causes IgAN. In IgAN, the substance that accumulates in the glomeruli is IgA (immunoglobulin A), an antibody produced by white blood cells. In some cases—though not all—IgA can activate the complement cascade, leading to C3 deposits.
Although C3G and IgAN are distinct diagnoses, as glomerular diseases, they share common therapeutic approaches.
ACE Inhibitors and ARBs
ACE (angiotensin-converting enzyme) inhibitors are medications that help control blood pressure by blocking the enzymes that narrow blood vessels.
Angiotensin II receptor blockers (ARBs) also help lower blood pressure. They work by relaxing blood vessels and refining the heart’s efficiency in pumping blood.
In cases of C3G and IgA nephropathy (IgAN), ACE inhibitors and ARBs help improve glomerular blood vessel function and reduce the strain that high blood pressure can place on the kidneys. These medications can also decrease proteinuria—that is, the amount of protein lost in the urine.
Steroids and immunosuppressants
There are two main ways to control the inflammatory processes that cause kidney damage in C3G and IgAN:
- reducing the immune system reply that leads to the formation of kidney deposits
- calming the inflammation caused by processes at the glomerular level
Steroids are medications known for their anti-inflammatory effects. Although long-term use is no longer recommended for C3G and IgAN, short courses of steroids are sometimes administered alongside immunosuppressive medications. Enteric-release budesonide (Nefecon) is considered a suitable treatment for IgAN.
C3G and IgAN are immune-mediated diseases. Their underlying causes stem from immune system dysfunction. Doctors use immunosuppressants to help control the body’s abnormal immune system reactions.
Many different immunosuppressants can be used depending on the diagnosis of C3G or IgAN.
According to a 2022 review on C3G, research findings regarding the efficacy of immunosuppressive therapy are mixed, and some people with C3G may experience greater benefits than others.
Complement inhibitors
Given that the complement system is a key component of C3G pathology, drugs that target the activation of the complement cascade represent an area of growing therapeutic interest.
Complement-targeting drugs, such as eculizumab and ravulizumab, work by blocking specific stages of the complement system, which regulates the production of the C3 protein. One of the most recently FDA-approved agents is iptacopan, an inhibitor of complement factor B. Iptacopan is approved for the treatment of both IgA nephropathy (IgAN) and C3G.
The efficacy of complement-targeting drugs can vary from person to person, and they may not be suitable for all cases of glomerular kidney disease.
Not all diagnoses of IgA nephropathy, for example, require the use of a complement inhibitor; however, if you have C3 accumulation, these drugs could be part of your treatment plan.
Plasma treatments
Plasma therapy, also known as plasmapheresis, is a treatment that uses a mechanism to filter blood and separate plasma from other blood components. Subsequently, a plasma substitute is administered to replace the plasma removed.
The complement proteins responsible for C3G are found in the plasma removed from the body. In addition to removing C3, plasma therapy can also remove immune complexes—such as IgA—and autoantibodies (antibodies that attack healthy cells).
Plasma therapy may not work in all cases. According to a 2019 review, there is no universally effective treatment or definitive cure, and further research into this therapy is required.
Kidney Transplant or Dialysis
As kidney function declines, your doctor may recommend more advanced treatments, such as dialysis.
Dialysis, like plasma therapy, involves machine-assisted blood filtration. In dialysis, the goal is to remove excess fluid and waste products from the blood, rather than from the plasma.
Dialysis does not directly treat C3G or IgAN; instead, it helps remove waste products from the body when the kidneys are no longer functioning properly.
In rare cases, a kidney transplantation may be an option. Because C3G and IgAN have underlying immunological causes and do not originate within the kidneys themselves, the use of transplantation as a treatment can be controversial.
Dietary changes and supplements
The National Kidney Foundation notes that both C3G and IgA nephropathy (IgAN) may benefit from reduced dietary salt and protein intake, which helps decrease the amount of waste crops the kidneys must filter from the bloodstream.
While research on the role of dietary supplements in treating these conditions is limited, there is evidence that omega-3 fatty acids, in the form of fish oil supplements, may offer anti-inflammatory benefits for IgA nephropathy.
Newer therapies
Nefecon, a special formulation of budesonide designed for targeted release in the intestine, is already considered a standard treatment.
More recently, in 2023, the FDA approved sparsentan (Filspari), a drug that also reduces protein excretion in the urine.
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, commonly used to treat diabetes, may also benefit patients with IgA nephropathy (IgAN). A review found that dapagliflozin reduced the risk of end-stage renal disease and improved survival in both individuals with type 2 diabetes and IgAN and in those with IgAN without diabetes.
Clinical trials for C3G and IgAN
According to ClinicalTrials.gov, there are more than 25 clinical trials across various phases for C3G, including several currently recruiting participants.
If you are interested in participating in clinical trials for C3G and IgAN, you can find more information by visiting:
Outlook
Now, here is no cure for kidney disease caused by C3G or IgAN. Both conditions are progressive, although treatment can slow or delay kidney damage.
According to a long-term study conducted in 2022, 30 years after diagnosis, between 20% and 50% of participants with IgAN had developed end-stage renal disease.
In the case of C3G, progressive kidney damage typically manifests after 10 years; by that time, up to half of patients have end-stage renal disease.
Given that C3G and IgAN are rare and understudied conditions, it is not yet possible to determine the extent to which treatment can improve the overall prognosis.
Key considerations
As glomerular diseases, C3G and IgAN require distinct therapeutic approaches, both aimed at controlling inflammatory processes and slowing kidney damage.
Your treatment plan may include blood pressure medications, immunosuppressants, and complement inhibitors.
Currently, there is no generally effective treatment or cure for C3G or IgAN. The effectiveness of each therapeutic option may vary depending on the individual being treated.