Dense deposit disease

Other Names: Glomerulonephritis membranoproliferative type 2; Mesangiocapillary glomerulonephritis type 2; MPGN 2; Membranoproliferative glomerulonephritis type II; DDD; Membranoproliferative glomerulonephritis type 2

Dense deposit disease (DDD) is a condition that primarily affects kidney function. The major features of DDD are due to kidney malfunction, and often include proteinuria; hematuria; reduced amounts of urine; low levels of protein in the blood; and swelling in many areas of the body. About half of affected people develop end-stage renal disease (ESRD) within 10 years after symptoms start.

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Cause

Dense deposit disease (DDD) can have genetic or non-genetic causes. When the condition is genetic, it may be associated with changes in several genes. Mutations that cause the condition have been identified in the C3 and CFH genes, but they account for only a small percentage of all cases. There are also variants of some genes (C3, CFH and CFHR5) that do not directly cause the condition, but increase the likelihood of developing the condition. Most people with these variants do not develop the condition. Most people with DDD do not have disease-causing mutations in the C3, CFH, or CFHR5 genes. The condition may develop due to a combination of genetic and environmental risk factors ("triggers"), most of which are unknown. The condition can also be caused by the presence of specific proteins called autoantibodies that block the activity of proteins needed for the body's immune response.

Inheritance

Most cases of dense deposit disease (DDD) are not inherited, but occur sporadically (in people with no history of the condition in the family). Only a few reported families have had more than one affected family member. The genetics of DDD is complex, and in many cases, its inheritance it is not completely understood. For these reasons, the exact recurrence risk for family members of most affected people is not known but is likely very low. In people with DDD that are known to have disease-causing mutations in the CFH gene, the inheritance pattern is autosomal recessive. The children of a person with autosomal recessive DDD will definitely be carriers of the condition. Carriers of autosomal recessive conditions typically do not have any signs or symptoms. Genetic carrier testing for at-risk family members is possible if the two CFH mutations have been identified in the affected family member. DDD has been seen in families in which other relatives have autoimmune disorders, such as celiac disease and type 1 diabetes mellitus.

Signs and symptoms

The major features of dense deposit disease (DDD) result from kidney malfunction. They usually include increased protein in the urine (proteinuria); the presence of blood in the urine (hematuria); reduced amounts of urine; low levels of protein in the blood; and swelling in many areas of the body. The kidney problems associated with DDD tend to worsen over time, and about half of affected people develop end-stage renal disease (ESRD) within 10 years after symptoms start. Some people with DDD develop a buildup of yellowish deposits called drusen in the retina of the eye. These deposits usually appear in childhood or adolescence and can cause vision problems later in life. The long-term risk of vision problems in people with DDD is about 10% (1 in 10). DDD can sometimes be associated with other conditions that are not related to kidney function. For example, it can occur with acquired partial lipodystrophy (APL), a condition characterized by a lack of fatty tissue under the skin of the upper body. In people with APL, the loss of fat in the upper body usually occurs several years before kidney disease starts.

Diagnosis

The GBM is rebuilt on top of the deposits, causing a "tram tracking" appearance under the microscope. Mesangial cellularity is increased.

Treatment

There is currently no specific treatment for dense deposit disease (DDD), but therapies are available to help slow the progression of the condition through aggressive blood pressure control and reduction of proteinuria. Both angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type-1 receptor blockers (ARBs) can be used to decrease the amount of protein in the urine and improve kidney function. These drugs may also limit the infiltration of white blood cells into the kidney. If hyperlipidemia (increased lipid in the blood stream) is present, lipid-lowering drugs may be used to reduce long-term risks of atherosclerosis. These drugs may also delay progression of kidney disease. Steroid therapy was widely used in the past, but more recent studies have shown that it is probably not effective for DDD. Steroid therapy is effective in a form of glomerulonephritis called juvenile acute non-proliferative glomerulonephritis (JANG), which is sometimes confused with DDD. People with DDD who develop end-stage renal disease typically need peritoneal dialysis or hemodialysis. Kidney transplant may be an option for some individuals; however, DDD will still develop in virtually all transplanted kidneys and about half of transplants will ultimately fail. There is some evidence that the likelihood of transplant failure due to recurrent DDD decreases with time.

NIH genetic and rare disease info

• NIH info on Dense deposit disease

Dense deposit disease is a rare disease.

Dense deposit disease Resources
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