C3 Glomerulopathy (C3G) and Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN): Symptoms, Causes, Diagnosis, Treatment, and More
Urological HealthKidney Diseases

What Are C3 Glomerulopathy (C3G) and Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)?

What Are C3 Glomerulopathy (C3G) and Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN)?
iStock; Everyday Health
By
Published on March 9, 2026
by

C3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are rare and progressive kidney diseases, caused by problems in the immune system. They are two distinct conditions, although there is significant overlap in symptoms and treatment.

In both C3G and IC-MPGN, part of the immune system known as the complement system becomes overactive. This in turn leads to inflammation and damage to the glomeruli in the kidneys, which are tiny networks of blood vessels that play an essential role in filtering blood and forming urine.

C3G and IC-MPGN can be challenging to diagnose because symptoms are nonspecific. They are lifelong, chronic diseases, and individuals with either condition face a high risk of progression to kidney failure. Studies have found that up to half of patients will develop kidney failure within 10 years of diagnosis.

While there is currently no definitive cure, new treatments that target the complement system have become available, with others in clinical trials. These have the potential to slow disease progression by targeting the underlying mechanisms.

Illustrative graphic titled How C3G and IC-MPGN Affect the Body shows Discolored Urine Foamy or Cloudy Urine Swelling High Blood Pressure Fatigue Less Urine Nausea and Vomiting Muscle Spasms. Everyday Health logo.
Everyday Health

Signs and Symptoms of C3G and IC-MPGN

Symptoms vary widely among individuals, and can be mild or severe. Kidney-related symptoms reflect the extent of damage in the glomeruli. In the early stages, there may be no obvious symptoms or signs of any problem, but as the disease progresses, symptoms may appear or intensify.

Even though their underlying mechanisms differ, both C3G and IC-MPGN disrupt the kidney’s ability to effectively filter waste, toxins, and excess fluid from the blood, resulting in similar signs and symptoms. These include:

  • Hematuria (Blood in the Urine) Your urine may look pink, red, or brown. Sometimes hematuria is not visible to the eye and can only be detected when the urine is analyzed.
  • Proteinuria (Excess Protein in the Urine) Urine may look foamy or cloudy.
  • Oliguria (Less Urine Production) As the disease progresses, you may find that you need to use the bathroom less often because your kidneys are producing less urine.
  • Edema (Swelling) Kidney disease can cause fluid to build up in your body. You may notice swelling, especially in your legs, ankles, and hands, or around your eyes.
  • Hypertension (High Blood Pressure) Fluid buildup can increase the force of blood pushing against your artery walls.
  • Fatigue or Lack of Alertness When kidneys can no longer remove waste from the blood efficiently, it accumulates in the blood. These waste products can affect the brain, making you feel tired or less alert.
  • Nausea and Vomiting Electrolytes may become imbalanced, and the blood more acidic (acidosis), if the kidneys are unable to flush out waste products efficiently.
  • Muscle Spasms at Night This symptom is also the result of electrolyte imbalance and acidosis.

Symptoms associated with C3G only include:

  • Acquired Partial Lipodystrophy This is an abnormal distribution of fat under your skin that can happen when disruption of the complement system destroys fat cells.
  • Drusen These small yellow deposits in your retina may develop from a buildup of complement proteins and fats.

Causes and Risk Factors of C3G and IC-MPGN

Both IC-MPGN and C3G are caused by dysfunction in the complement system, resulting in a buildup of deposits in the kidney’s filtering system. C3G causes the breakdown of normal complement proteins including C3. The protein fragments accumulate in the kidney which leads to inflammation and damage to the glomeruli. In IC-MPGN, the dysfunction in the complement system causes deposits in the kidneys of both C3 and other proteins and antibodies.

It’s unclear what causes the complement system to malfunction. In C3G, it’s believed that the complement system is triggered for two main reasons.

  • Genetic changes that occur in proteins that help regulate the system. About a quarter of patients have genetic mutations or variants in these complement-related genes.
  • The development of antibodies that target and attack your own body’s healthy cells and tissue (autoantibodies)
In IC-MPGN, complement system dysfunction is often associated with other diseases. These include:

  • Autoimmune diseases such as lupus and rheumatoid arthritis
  • Chronic infections such as hepatitis B or C and HIV
  • Cancers including leukemias, lymphomas, and carcinomas
  • Sickle cell disease

How Are C3G and IC-MPGN Diagnosed?

Initial symptoms of C3G and IC-MPGN are nonspecific and may often be overlooked. Making a diagnosis involves blood and urine tests, and importantly, a kidney biopsy.

Initial testing may include:

  • Urinalysis to check your urine for any signs of health issues and to measure protein and blood levels
  • Blood tests to show how efficiently your kidneys are getting rid of waste products in your blood, including your estimated glomerular filtration rate (eGFR) and serum creatinine level
  • Kidney biopsy is the only way to definitively confirm a diagnosis of C3G or IC-MPGN. The biopsied tissue is examined using a technique called immunofluorescence microscopy, which can differentiate C3G from IC-MPGN and other similar disorders.
After your diagnosis is confirmed, your doctor may order additional tests that can guide treatment. These include:

  • Advanced complement system testing to measure the activity of complement proteins and look for abnormalities
  • Blood tests to find out whether you have an autoimmune disease or infections
  • Genetic testing to see if you have an inherited form of IC-MPGN

Treatment and Medication Options for C3G and IC-MPGN

There is no standard treatment for C3G and IC-MPGN, as symptoms and severity can vary tremendously from person to person. Instead, a treatment plan is tailored to an individual’s situation, taking into account factors such as age, overall health, severity of symptoms, genetics, and cause of the illness.

The goal of treatment is to reduce inflammation and slow down kidney damage to prevent kidney failure. It often includes a combination of medications and lifestyle measures. If C3G or IC-MPGN progresses to the point of kidney failure, you would need dialysis or a kidney transplant.

Medication Options

Angiotensin-Converting Enzyme Inhibitors (ACE Inhibitors) and Angiotensin Receptor Blockers (ARBs)

ACE inhibitors and ARBs are widely used to control blood pressure and lower the amount of protein in your urine to slow down kidney damage. Examples include:

  • lisinopril (Zestril)
  • enalapril (Vasotec)
  • losartan (Cozaar)
  • valsartan (Diovan)

Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors

SGLT2 inhibitors are medications that are primarily used to treat type 2 diabetes. But they help protect your kidneys by blocking sugar from being reabsorbed there. SGLT2 inhibitors slow the progression of kidney disease and lower the risk of eventually needing to go on dialysis. Some drugs in this class are:

  • bexagliflozin (Brenzavvy)
  • canagliflozin (Invokana)
  • dapagliflozin (Farxiga)
  • empagliflozin (Jardiance)
  • ertugliflozin (Steglatro)

Immunosuppressive Therapy

These medications are used to “calm” or suppress the immune system when it becomes overactive and mistakenly harms the body. Your doctor may recommend:

  • prednisone
  • mycophenolate mofetil (CellCept)
  • cyclophosphamide
  • rituximab (Rituxan)

Complement Inhibitors

This newest class of drug treatment for C3G and IC-MPGN directly addresses the underlying mechanism of the diseases. Complement inhibitors lower the activity of the complement system and reduce damage to the glomeruli, which stabilizes kidney function. Several medications may be used:

  • iptacopan (Fabhalta) is an oral medication approved in March 2025 to treat C3G.
  • pegcetacoplan (Empaveli) is an injectable drug approved in July 2025 for both C3G and IC-MPGN.
  • eculizumab (Soliris) is an injectable monoclonal antibody that has been used off-label to treat C3G and IC-MPGN.

Researchers are testing many other complement inhibitors in clinical trials.

Other Treatments

Plasma exchange (plasmapheresis) is a blood filtering process that can remove harmful antibodies and other substances from the blood. It’s generally only used for those with rapidly progressing disease or who are resistant to immunosuppressive therapies.

Dialysis is a treatment that removes excess fluid and waste products from your blood when your kidneys can no longer do so. Your doctor may recommend dialysis when symptoms and signs of kidney failure begin to appear. Dialysis is often the “bridge” to a transplant.

Kidney transplant may be needed if your disease progresses to kidney failure. Immunosuppressive medications are required to prevent your body from rejecting the organ. Other medications will still be needed to control the dysfunctional complement system, since the risk of recurrence in the transplanted kidney is high.

Lifestyle Changes for C3G and IC-MPGN

In addition to medications, lifestyle changes can help you stay as healthy as possible. They can help you control associated problems, such as high blood pressure, and reduce the risk of complications that can further damage your kidneys.

Make Changes to Your Diet

While there is no single standard meal plan for everyone with kidney disease, there are general recommendations that can help reduce inflammation and protect your kidneys.

  • Lower your intake of salt (sodium). Keeping salt intake low helps balance fluids, control your blood pressure and reduce proteinuria.
  • Limit protein intake. A low-protein diet is usually recommended to help preserve kidney function. It helps reduce the kidney’s workload and lowers the amount of waste buildup in the blood. But protein requirements will differ depending on the severity of your symptoms.
  • Maintain a healthy weight. Talk to your doctor about what is an ideal weight for you and aim to reach it.
  • Choose heart-healthy foods. You can lower your risk of developing heart and vascular (blood vessel) disease by replacing saturated fats and trans fats, eating fresh fruits and vegetables, and choosing whole grains and lean, unprocessed proteins.
  • Minimize alcohol intake. Drinking alcohol can be harmful to kidneys and may lead to high blood pressure and dehydration. It can also have a negative impact on existing kidney disease.

Get Regular Exercise

Everyone can benefit from regular exercise, including individuals living with chronic kidney conditions. Physical activity is important at all stages of kidney disease, even if you are currently on dialysis or have undergone a transplant. It can benefit your body in many ways, including strengthening your heart, building muscle and strength, and boosting energy. Exercise can even help you feel less stressed or anxious. In addition, regular exercise may improve your blood sugar levels if you have diabetes, and some studies suggest that it may improve your kidney function.

Here are some tips to get started.

  • Speak with your doctor and healthcare team before you begin any exercise program.
  • You’re more likely to stick with it if you find activities that you enjoy.
  • Your healthcare team may recommend changes to your diet, especially if you have diabetes, once you begin to exercise.
  • To stay safe and prevent injury, make sure you have the correct gear, do warm-ups, and start off slow.

Get Regular Checkups

You’ll need follow-up testing for the rest of your life to watch for signs that the disease is progressing. Your doctor will check your blood pressure and do blood and urine tests to check your kidney function.

C3G and IC-MPGN Prognosis

Both C3G and IC-MPGN are lifelong conditions. While treatment can slow down progression, or even halt it, there is currently no cure. The goal of treatment is to reduce kidney damage and delay or even prevent the onset of kidney failure.

As many as half of all patients will reach end-stage renal disease or kidney failure within 10 years after receiving their diagnosis, and will need to go on dialysis and possibly receive a transplant.

 But it’s difficult for doctors to predict who will progress to kidney failure, and some people live for years without complications.

Your individual prognosis depends on many factors, including the presence or absence of genetic mutations, the presence of autoantibodies, the degree of kidney damage at diagnosis, and how well the disease responds to treatment.

Better outcomes can be expected if the disease is caught early, if your blood pressure is well-controlled, and you get treatment for underlying triggers. It’s also important to stick with your treatment plan.

Complications of C3G and IC-MPGN

The major complication of these disorders is kidney failure. When that happens, the kidneys are no longer able to function effectively and you’ll need dialysis and possibly a kidney transplant.

Other complications include:

  • High blood pressure, which increases the risk for heart disease
  • High cholesterol
  • Medication side effects, including an increased risk of serious infections
  • A high risk of disease recurrence after transplant

Support for People With C3G and IC-MPGN

NephCure

NephCure is a kidney organization focused on rare, protein-spilling kidney diseases. The website contains information about rare kidney disease, diagnosis, disease management, and advocacy and they offer virtual support groups, regional events, and an online community for patients and caregivers.

The Takeaway

  • C3G and IC-MPGN are rare, chronic, and progressive kidney diseases that are caused by an overactive complement system (part of the immune system).
  • Diagnosis is through a kidney biopsy, with special testing on the tissue sample to differentiate between the two diseases.
  • Both diseases have a high risk of progression to serious kidney damage and kidney failure.
  • Emerging therapies that target the complement system show promise and could change the course of the disease.

FAQ

Are the new complement inhibitors more effective than other treatments?
These drugs represent a major shift from nonspecific immunosuppression to targeting the underlying mechanism of the disease.
Yes, lifestyle changes including a “kidney healthy diet,” regular exercise, and minimizing alcohol and cigarette use can help decrease the likelihood of kidney damage.
The course of the disease is very variable, and not everyone will need a transplant. The best way to minimize kidney damage is to stick to your treatment plan.
In most cases, it is unclear why these diseases develop and there is no definitive way to prevent them.

Resources We Trust

EDITORIAL SOURCES
Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.
Resources
  1. C3 Glomerulonephritis & IC-MPGN. European Rare Kidney Disease Reference Network.
  2. Caravaca-Fontán F et al. Clinical Presentation, Treatment Patterns, Burden of Disease, and the Association of Proteinuria with Clinical Outcomes in C3 Glomerulopathy and Primary Immune Complex Membranoproliferative Glomerulonephritis: A Systematic Review. Nephron. September 19, 2025.
  3. Kavanagh D et al. Current and Emerging Therapies for C3 Glomerulopathy and Primary (Idiopathic) Immune Complex Membranoproliferative Glomerulonephritis. Kidney International Reports. November 5, 2025.
  4. C3 Glomerulonephritis & IC-MPGN. European Rare Kidney Disease Reference Network.
  5. Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN). National Kidney Foundation. October 16, 2025.
  6. Complement 3 Glomerulopathy (C3G). National Kidney Foundation. July 25, 2025.
  7. Ayehu G et al. C3 Glomerulopathy. StatPearls. November 5, 2024.
  8. Kazi AM et al. Glomerulonephritis. StatPearls. June 26, 2023.
  9. Mashayekhi M et al. C3 Glomerulopathy Diagnosis, Current Treatments, and Emerging Therapies. Kidney Medicine. March 2026.
  10. Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN). NephCure.
  11. Noris M et al. C3G and Ig-MPGN—Treatment Standard. Nephrology Dialysis Transplantation. August 2, 2023.
  12. Complement 3 Glomerulopathy (C3G). American Kidney Fund. June 25, 2025.
  13. ACE Inhibitors and ARBs. National Kidney Foundation. May 4, 2023.
  14. SGLT2 inhibitors. National Kidney Foundation. December 6, 2024.
  15. Gregory SY. What to Know About C3G Treatments, From Lifestyle Adjustments to Medications and Dialysis. Mayo Clinic. May 14, 2025.
  16. Healthy Eating for Adults With Chronic Kidney Disease. National Institute of Diabetes and Digestive and Kidney Diseases. January 2025.
  17. Alcohol and Your Kidneys. National Kidney Foundation.
  18. Exercise and Chronic Kidney Disease. National Kidney Foundation. October 8, 2025.
  19. Chronic Kidney Disease, Dialysis, and Keeping Fit. National Kidney Foundation.
Meet Our Experts
See Our Editorial PolicyMeet Our Health Expert Network
igor-kagan-bio

Igor Kagan, MD

Medical Reviewer
Castle Connolly Top Doctor

Igor Kagan, MD, is an an assistant clinical professor at UCLA. He spends the majority of his time seeing patients in various settings, such as outpatient clinics, inpatient rounds, and dialysis units. He is also the associate program director for the General Nephrology Fellowship and teaches medical students, residents, and fellows. His clinical interests include general nephrology, chronic kidney disease, dialysis (home and in-center), hypertension, and glomerulonephritis, among others. He is also interested in electronic medical record optimization and services as a physician informaticist.

A native of Los Angeles, he graduated cum laude from the University of California in Los Angeles (UCLA) with a bachelor's in business and economics, and was inducted into the Phi Beta Kappa honor society. He then went to the Keck School of Medicine at the University of Southern California (USC) for his medical school education. He stayed at USC for his training and completed his internship and internal medicine residency at the historic Los Angeles County and USC General Hospital. Following his internal medicine residency, Kagan went across town to UCLA's David Geffen School of Medicine for his fellowship in nephrology and training at the UCLA Ronald Reagan Medical Center. After his fellowship he stayed on as faculty at UCLA Health.

See full bio
Roxanne Nelson

Roxanne Nelson, RN

Author

Roxanne Nelson is a registered nurse (RN) and a medical and health writer. Her work has been published by a range of outlets for both healthcare professionals and the general public, including Medscape, The Lancet, The Lancet Infectious Diseases, The Lancet Microbe, American Journal of Medical Genetics, American Journal of Nursing, Hematology Advisor, MDEdge, WebMD, National Geographic, Washington Post, Reuters Health, Scientific American, AARP publications, and a number of medical trade journals. She has also written continuing education programs for physicians, nurses, and other healthcare professionals.

She specializes in writing about oncology, infectious disease, maternal and newborn health, pediatric health, healthcare disparities, genetics, end of life, and healthcare cost and access. As an RN, she worked in newborn and pediatric intensive care, especially in settings with high rates of HIV infection and hepatitis B, and also in case management of NICU "graduates" who were now being cared for the home setting.

An avid traveler, Roxanne has explored the globe and stepped foot on all seven continents. Some of her travel had a medical and healthcare focus, while the rest was pure adventure. She lives in the Seattle metro area with her partner and two cats, although that number tends to change!

See full bio
See Our Editorial PolicyMeet Our Health Expert Network