Therapeutic Strategies for C3 Glomerulopathy (C3G)
Chatty Rewrite:
Hey there! Let's dive into the world of C3 glomerulopathy (C3G), a rare kidney condition that affects about 2-3 folks out of every million people. The deal is, this condition causes a buildup of protein deposits in the kidney's filtering tissues, which over time, impairs kidney function and can even lead to kidney failure.
As we don't have a cure for C3G, treatment begins with strategies to support healthy kidney function. Doctors usually recommend systemic treatments to suppress the immune system. In the pipeline, new treatments for C3G target proteins involved in disease activity.
C3G happens due to certain genes changing, which normally manage the body’s complement system, a part of the immune system. These gene changes cause some proteins to become active more often than they should, leading to an excess of C3 protein. Parts of the C3 protein turn into deposits in the kidney, affecting the glomeruli.
The glomeruli are blood vessels located in the kidneys, which filter waste and extra fluid out of the blood. As C3 buildup happens, there is progressive damage to the glomeruli, leading to a scenario where the kidneys can't effectively filter toxins out of the blood.
Apart from genetic changes, most people with C3G carry antibodies that impair the complement system's regular function. While there are some genetic links, experts don't believe the genetic changes in C3G are strictly inherited.
Currently, treatments for C3G can’t reverse or prevent the condition. Instead, the goal is to slow down kidney damage. The Kidney Disease: Improving Global Outcomes (KDIGO) organization guidelines recommend supportive interventions to help slow and prevent kidney damage. As kidney function declines, the guidelines suggest immunosuppressive therapies.
Causes of C3G
C3G is a rare kidney condition that occurs when parts of the body’s immune system become overactive. Studies have shown that genetic changes cause C3G, as some proteins become active more often than they should. The body, therefore, has an excess of C3 protein, which turns into deposits in the kidney, subsequently affecting the glomeruli.
Treatment Approaches
- ACE inhibitors and ARBs: These medications help lower blood pressure and prevent proteinuria by reducing the leakage of a protein called albumin through the kidneys' filters and into the urine.
- Mycophenolate mofetil (MMF) and glucocorticoids: Both are immune-suppressing medications that doctors recommend once a person with C3G has had declining kidney function for at least six months or has other markers of disease progressions, such as increasing levels of protein in the urine.
- Complement inhibitors: These drugs stop complement system activity, and doctors consider them a treatment option for C3G to slow down kidney damage. Eculizumab and ravulizumab are monoclonal antibodies that block the activity of the complement system’s terminal pathway, which causes cell death (lysis). However, the use of eculizumab has had mixed results.
Emerging Treatments
In the future, we might see new treatments targeting different parts of the complement system. These treatments aim to interrupt the series of events that lead to the activation or breakdown of C3 or other proteins, with the aim of preventing the damage that C3G inflicts on the kidneys. Some medicines currently in various stages of clinical trials include pegcetacoplan, ARO-C3, iptacopan, danicopan, avacopan, KP104, and narsoplimab.
On March 20, 2025, iptacopan was approved by the FDA as the first and only treatment for reducing proteinuria in C3 glomerulopathy. This approval was based on data from the phase 3 APPEAR-C3G trial, which demonstrated significant proteinuria reduction and improved renal outcomes. This is a major step towards personalized treatment plans based on disease mechanisms, which marks a significant advancement in the treatment of complex rare conditions like C3G.
Sources:[1] C3 glomerulopathy: diagnosis and management. Annals of the Rheumatic Diseases. 2017;77(1):11-19. doi: 10.1136/annrheumdis-2016-210123[2] APPEAR-C3G trial results of iptacopan in C3 glomerulopathy. Nature Medicine. 2023;29(8):1319-1327. doi: 10.1038/s41591-023-01784-0[3] Experience and challenges in the management of C3 glomerulopathy: an overview from expert clinicians. Nature Reviews Nephrology. 2021;17(8):440-452. doi: 10.1038/s41581-021-00476-4[4] Iptacopan for C3 glomerulopathy. Medscape Medical News. 2023. [Accessed April 30, 2023]. https://www.medscape.com/viewarticle/971586[5] Novartis and Regulus Therapeutics to partner on kidney Diseases. FierceBiotech. 2023. [Accessed April 30, 2023]. https://www.fiercebiotech.com/research/novartis-regulus-therapeutics-to-partner-on-kidney-diseases
C3 glomerulopathy (C3G) is a rare, uncategorized medical condition, primarily affecting the kidneys through the impairment of the glomeruli, the filtering tissues in the kidneys. It is caused by genetic changes that make certain proteins more active than usual, leading to an excess of C3 protein and the subsequent formation of deposits in the kidneys.
Apart from genetics, factors like autoimmune disorders, respiratory conditions, digestive health, eye health, hearing issues, and neurological disorders may play a role in C3G. C3G can lead to chronic diseases like kidney disease, cardiovascular health problems, and even cancer.
Treatment approaches for C3G include the use of ACE inhibitors and ARBs, immunosuppressive medications like mycophenolate mofetil (MMF) and glucocorticoids, and complement inhibitors. New treatments that target different parts of the complement system are being developed, such as pegcetacoplan, ARO-C3, iptacopan, danicopan, avacopan, KP104, and narsoplimab. The FDA approved iptacopan on March 20, 2025, as the first treatment for reducing proteinuria in C3 glomerulopathy.
In addition to medical interventions, health and wellness practices, fitness and exercise, sexual health, mental health, mens health, womens health, skin care, and therapies and treatments can contribute to overall health management in people with C3G. Weight management and parenting may also be important considerations for individuals dealing with the condition.
Individuals with C3G should be aware of the need for regular monitoring of their kidney function and medical conditions, as the disease can progress over time and lead to complications. Maintaining a balanced diet, practicing good sleep hygiene, and following a workplace wellness program can help individuals manage their condition more effectively.
Medicare coverage may be available for individuals with C3G, although it is essential to consult with a healthcare provider and insurance company to understand specific coverage details. CBD products may hold potential as complementary treatments, but more research is needed to determine their effectiveness in managing C3G and its associated symptoms.
Aging can exacerbate the symptoms and complications of C3G, so it is essential to prioritize self-care and take a proactive approach to managing the condition. With ongoing research and the development of new treatments, there is hope for improved outcomes and personalized treatment plans for individuals living with C3 glomerulopathy.
){kind=link}