Q: What is C3G, DDD and C3GN?

A: DDD stands for Dense Deposit Disease (DDD). DDD used to be called MPGN Type 2 (membranoproliferative glomerulonephritis type II). As our understanding of the disease has evolved, the name has changed. DDD is a kidney disorder that stops the kidneys from correctly filtering waste from the blood. The immune system of persons with DDD does not work correctly and deposits  build up in the kidneys. These deposits are located in the filtering part of the kidney, which is known as the glomerulus. Glomeruli become inflamed and their ability to filter and clean the blood is destroyed.

In 2013, a group of scientists convened in England and recommended adopting the umbrella term C3 Glomerulopathy (C3G), which includes both DDD and C3GN (C3 glmoerulonephritis). DDD and C3GN are differentiated from each other by electron microscopic examination of the kidney biopsy.

 

Q: How are DDD and C3GN diagnosed?

A: To find out if you have DDD of C3GN, you need a kidney biopsy. A small amount of tissue is taken from your kidneys and studied under a microscope in several ways. Immunofluorescence microscopy will show C3 deposition. Electron microscopy will show dense deposits in DDD and lighter deposits in C3GN.  

 

Q: What causes C3G?

A: C3G is caused by uncontrolled activity of the alternative pathway of the complement cascade.

 

Q: What is the complement cascade?

A: The complement cascade is an important part of the immune system that helps the body fight infections. Activation of the complement cascade starts a chain reaction to kill bacteria and viruses, and clear the blood stream of dead cellson infected cells.

 

Q: Why is uncontrolled activation of the complement cascade so bad?

A: Uncontrolled activity of the complement cascade means that complement activity is constantly on-going and is running unchecked and out of control. Normally, the complement system defends the body from an invader, but when activity is not controlled, damage to the body can occur. In C3G, the kidneys are damaged. The eyes can be damaged as well.

 

Q: What happens to someone with C3G?

A: About half of people with C3G progress to kidney failure over time. If you go into kidney failure, your kidneys don’t work well enough to keep you alive. You need dialysis or a kidney transplant to live. Different studies report different statistics about the amount of time that it takes for a person with the diagnosis of DDD to go into kidney failure. In about half of people diagnosed with DDD, their kidneys fail in 8-12 years; in 85% of people, their kidneys fail within 20 years (50% Habib et al. (1987); 67% Davis, et al (1978); 11% McEnery et al. (1980) 61% Cameron(1982); 76% Schwertz, et al(1996)). In C3GN, the rate of progression to kidney failure is not as rapid as it is with DDD. Good data on C3GN are lacking as this term was adopted only recently.

 

Q: What is the current treatment for C3G? What about Eculizumab?

A: There is currently no treatment that is specific for DDD or C3GN, however there are promising drugs on the horizon. There are also standard (general) ways to treat people who are developing kidney disease, and you should discuss these treatment options with your doctor. MMF appears to be beneficial in about 30% of persons with C3GN.

Eculizumab is an anti-complement drug. It halts complement activity at the level of the terminal pathway. In C3G, dysregulation occurs before this point. For that reason, Eculizumab is not universally helpful as a treatment for C3G. Nevertheless, about 30% of patients may receive some benefit. It may be possible to identify patients likely to benefit by studying complement biomarkers.

 

Q: Can you get a transplant if you have C3G?

A: Yes, you can get a kidney transplant. In most cases, C3G recurs in the transplanted kidney. Eddy et al (1984) reports that 5 of 10 transplanted kidneys were lost due to recurrent DDD between 9 months and 8 years following transplantation in 4 of 6 individuals. These figures suggest that half of the transplanted kidneys eventually fail due to recurrent disease. The outcome for C3GN appears to be similar (Zand et al JASN, 2013).

 

Q: When should a transplant be done?

A: This decision should be made by you and your physician. Although there is a high risk of recurrence on biopsies of transplanted kidneys, some people do well for years.

 

Q: I have heard that C3G also affects the eyes. What happens?

A:  Deposits similar to the deposits found in the kidney can be found in the eye. These deposits are called drusen. The amount of drusen is not related to disease activity. Some people who go into kidney failure quickly have no drusen, and some who have no kidney problems have drusen. The amount of drusen a person has does seem to be related to the amount of time they have had C3G, and so drusen are more likely to be found in persons who have had C3G for a long time. Some studies have suggested that after about 20 years, drusen may cause problems with color discrimination, night vision and occasionally, loss of vision. Although there is no current treatment for drusen, people with C3G should be followed by an ophthalmologist.

 

Q: Is C3G a genetic disease?

A:  C3G is a complex genetic disease. Persons can inherit a predisposition to developing C3G, however gene mutations are not the only factor that leads to the development of C3G. There are additional trigger(s) that start the disease process, but we do not know what these triggers are.