Questions and answers about DDD / MPGN II
Q: What is DDD/MPGN II?
A: DDD/MPGN II goes by a number of names besides Dense Deposit Disease and membranoproliferative glomerulonephritis type II, including mesangial proliferative glomerulonephritis and mesangial capillary glomerulonephritis. It is a kidney disorder that stops the kidneys from correctly filtering waste from the blood. The immune system of persons with DDD/MPGN II does not work correctly and deposits to 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. For more on how your kidneys work and what happens when they don’t, click here.
Q: How is DDD/MPGN II diagnosed?
A: To find out if you have DDD/MPGN II you will need to have a kidney biopsy. Your doctor will take a small amount of tissue from your kidneys and look at it under an electron microscope to see if dense deposits are there. This is why the disease is called Dense Deposit Disease. The deposits don’t show up as well under a light microscope, so it is necessary to have the tissue from your kidney biopsy looked at with an electron microscope.
Q: What causes MPGN II/DDD?
A: DDD/MPGN II is caused by uncontrolled activity of the alternative pathway of the complement cascade. In a few persons with DDD/MPGN II, disease-causing mutations can be found in a gene called Factor H. This gene makes a protein also called factor H that helps to regulate the complement cascade.
Q: What is the complement cascade?
A: The complement cascade is a part of the immune system that helps the body fight infections. The complement group of proteins assists in killing bacteria, viruses, or infected cells. The complement cascade is like a chain reaction that causes an attack on infected cells. The alternative pathway is one of three different complement pathways that are known. For more on the complement cascade and the immune system click here.
Q: Why is uncontrolled activation of the complement cascade so bad?
A: Uncontrolled activity of the alternative pathway of complement means that the alternative pathway is constantly on and is running unchecked and out of control. Normally, the alternative pathway should defend the body from an invader but when the alternative pathway is out of control, it does not know when to stop. It will attack both infections and the body. In DDD/MPGN II, the kidneys and eyes are damaged.
Q: What happens to someone with DDD/MPGN II?
A: Most people with DDD/MPGN II 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/MPGN II to go into kidney failure. In about half of people diagnosed with DDD/MPGN II, 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)).
Q: What is the current treatment for DDD/MPGN II?
A: There is currently no treatment that is specific for DDD/MPGN II, 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. You should also ask your doctor about genetic testing. In a few people with DDD/MPGN II, disease-causing mutations are present in a gene called Complement Factor H (CFH). If mutations are found in this gene, replacement of Factor H (by plasma exchange or infusion) may prevent progression of kidney disease.
Q: Can you get a transplant if you have DDD/MPGN II?
A: Yes, you can get a kidney transplant. In most cases, DDD/MPGNII recurs in the transplanted kidney. Eddy et al (1984) reports that 5 of 10 transplanted kidneys were lost due to recurrent DDD/MPGN II 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.
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, some people do well for several years. You need to weigh how you are doing on dialysis, the waiting period on the transplant list or availability of a living donor, and your quality of life. Transplantation also has problems, and those need to be considered when you are deciding whether to transplant or stay on dialysis.
Q: What happens when you are on dialysis?
A: Today there are many dialysis options. For the most recent dialysis information, please click on our links to dialysis sites: Mayo Clinic, Home Dialysis, KidsHealth (for children).
One problem that these sites do not address is sclerosing encapsulating peritonitis. This problem causes a cocoon of scar-like fibers in the peritoneal cavity (the lining of the abdomen that is used for dialysis). The fibers wrap themselves around the intestines shutting off the blood supply and squeezing the intestines so that food cannot travel down the intestines properly. The result is a partial small bowel obstruction.
Without surgery or treatment this problem can be very serious. Sclerosing encapsulating peritonitis can happen to people who are on peritoneal dialysis for five or more years. It is not seen in the United States very often because most people in renal failure tend to transplant within a few years. Anyone who is on peritoneal dialysis for more than five years should be aware of this potential problem as it can be life threatening.
The cause of sclerosing encapsulating peritonitis is not well known. Some scientists think it may be associated with products in the dialysis fluid or infections. But it can also happen in the absence of prior infections and it has even been found in one person on hemodialysis who was never on peritoneal dialysis. The longer a person is on peritoneal dialysis, the greater their risk of developing sclerosing encapsulating peritonitis. For more information on sclerosing encapsulating peritonitis see "Sclerosing Peritonitis: the experience in Australia" by Rigby, RJ and Carmel GM. (1998)
Q: I have heard that DDD/MPGN II 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 DDD/MPGN II, and so drusen are more likely to be found in persons who have had DDD/MPGN II 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 DDD/MPGN II should be followed by an ophthalmologist. New therapies are now being tried in adults with age-related macular degeneration (AMD). AMD is very similar to the drusen in DDD/MPGN II and so the same therapies may be helpful for persons with DDD/MPGN II.
Q: Is DDD/MPGN II a genetic disease?
A: Persons with DDD/MPGN II have a complex genetic disease. Persons can inherit a predisposition to developing DDD/MPGN II. However genes are not the only factor. There are additional trigger(s) that start the disease process, but we do not know what these triggers are. Consider, for example, a light bulb. Even if the wires connect the light bulb to the power source, without someone (the trigger) to turn on the switch, you won’t have light. We know of one set of identical twins, where one twin is in renal failure from DDD/MPGN II, and her identical twin does not have the disease.
Information provided by Richard J.H. Smith, MD.
Last updated 10/29/09