C3 Glomerulopathy (formerly known as MPGN) C3G stands for Complement 3 Glomerulopathy, a very rare and chronic disease that causes the kidneys to not work properly. C3G used to be called Membranoproliferative Glomerulonephritis (MPGN) 1, 2, or 3, but healthcare professionals have changed how they classify and talk about this disease. Old TermNew TermMPGN 1 IC-MPGN (Immune-Complex MPGN)MPGN 2Dense Deposit Disease (DDD)MPGN 3C3 Glomerulonephritis (C3GN) Overview and symptoms C3G stands for Complement 3 Glomerulopathy, a very rare and chronic disease that causes the kidneys to not work properly. The C3 refers to a key blood protein that plays an important role in your immune system. The G stands for glomerulopathy, or damage to the filtering units of the kidney (the glomeruli). Physician experts believe that when complement proteins like C3, which are part of your immune system, are not well-controlled, it results in damage to the kidneys’ filtering units. Some symptoms of C3G include: High levels of protein in urine (proteinuria) Blood in urine (hematuria) Low levels of protein in the blood (hypoalbuminemia) Swelling in many areas of the body (edema) Fatigue Dark and/or foamy urine High blood pressure (hypertension) Decreased urine output High levels of creatinine in the blood due to your kidneys not filtering properly. Find out more about your lab values here. Some C3G patients experience vision difficulties from lipid & protein deposits that develop under the retina, called drusen How is C3G diagnosed? There are three forms of C3G: Immune-complex MPGN (IC-MPGN) [formerly called MPGN 1] Dense Deposit Disease (DDD) [formerly called MPGN 2] C3 Glomerulonephritis (C3GN) [formerly called MPGN 3] To diagnose C3G, doctors examine a tiny portion of the kidney tissue in a procedure called a biopsy AND conduct blood tests to look at levels of specific complements, including C3, C4, and C5. Between 10-25% of all C3G diagnoses are genetically linked. Other diagnostic tools may include: Urinalysis: determines the amount of protein in the urine Blood work: determines levels of creatinine, albumin, cholesterol, and many other factors examined to rule out other causes Glomerular filtration rate (GFR): Your GFR estimates your kidney function by calculating blood creatinine levels with urine protein levels. Click here for a GFR calculator. Ultrasound: sometimes performed to get a closer look at the kidneys Who gets C3G? C3G affects 2-3 individuals out of every 1 million people. It affects people of all ages, but the IC-MPGN form tends to be more common in children than adults. What causes C3G? C3G occurs when a part of your immune system called "the complement system" becomes overactive or dysfunctional. If the complement system becomes overactive, the C3 complement proteins are broken down and get trapped in the filtering units of your kidneys (the glomeruli). The trapped C3 then causes a series of reactions that damage the glomeruli. How is C3G treated? There are currently no FDA-approved medicines to treat C3G. The short-term goal of treatment is to stop protein spillage completely (known as remission) or lower the amount of protein lost in the urine as much as possible. The less protein lost in the urine, the better the patient will do. The long-term goals of treatment include preventing relapses of protein in the urine and preventing the deterioration of kidney function. Standard first-line (initially prescribed) treatments for C3G are blood pressure medications, like lisinopril and ibesartan, and immunosuppressants, like steroids and mycophenolate mofetil (MMF or CellCept). Patients have varying degrees of success with these forms of medical treatments. Children with C3G tend to be more responsive to treatment than adults. However, there are many new, potential treatment options based on new understanding of C3G that are being studied in clinical trials right now. All treatment options being studied are complement-targeted therapies that specifically target areas of the alternative pathway, rather than the classical pathway, to stop progression of the disease. Visit KidneyHealthGateway.com to learn more about current clinical trials for C3G patients. Your nephrologist may also recommend: Medications that suppress your immune system Diuretics and a low-salt diet to help control edema A medication that blocks a hormone system called the renin angiotensin system (ACE inhibitor or ARB) to control blood pressure or lower urine protein Anticoagulants to prevent blood clots Statins to lower the cholesterol level Maintaining a healthy diet and regulating protein and fluid intake according to your nephrologist's recommendations. A healthy diet consists of low-sodium foods with an emphasis on fruits and vegetables that are low in saturated fat and cholesterol. Exercising Not smoking Taking vitamins Living with C3G 1. Following a low-sodium diet and taking prescribed medications from your nephrologist may help improve your kidneys’ function and your C3G symptoms. 2. Finding a nephrologist that specializes in C3G that you trust is very important to your long-term health. 3. Learn about your disease, treatment options, and clinical trials in order to better advocate for yourself. 4. NephCure Kidney International can help you connect with other patients and find support to manage your disease. Prognosis of C3G The chance of C3G patients achieving remission spontaneously is relatively low. However, studies have shown that, in some cases, patients may remain stable for years before their condition worsens, even if they continue spilling protein. Nearly half of C3G patients develop end-stage kidney disease within 5 years of their clinical diagnosis. The future of C3G There are currently no FDA-approved medicine treatments for C3G — but right now, the future looks more promising than ever before. There are at least 20 potential new medicines for Nephrotic Syndrome diseases in various phases of clinical trials. Clinical trials in C3G are specifically targeting the cause (and progression) of the disease, aiming to expand options to treat C3G diseases more specifically at their root cause. These clinical trials are absolutely essential in making new treatments possible, and they need patient involvement to succeed. That's why NephCure launched KidneyHealthGateway.com, an online platform that connects Nephrotic Syndrome patients with clinical trials in order to advance research and eventually find a cure for C3G and other protein-spilling kidney diseases. Access breakthrough clinical trials, expert care, and one-on-one patient support all in one place — visit KidneyHealthGateway.com to find the clinical trial right for you. Interested in learning more about C3G? The C3G landscape is changing fast! Dr. Marina Vivarelli discusses new innovations and learning in this webinar from the 2021 NephCure Patient Summit. References1. NORD (National Organization for Rare Disorders): https://rarediseases.org/rare-diseases/c3-glomerulopathy-dense-deposit-disease-and-c3-glomerulonephritis/ 2. Caravaca-Fontán F, Lucientes L, Cavero T, Praga M: Update on C3 Glomerulopathy: A Complement-Mediated Disease. Nephron 2020;144:272-280. Download this information as a PDF here This educational content is sponsored by Apellis Pharmaceuticals.