Understanding a rare kidney disease diagnosis can be complicated. Dense deposit disease (DDD) is a type of C3 glomerulopathy (C3G) — a rare disease that happens when the complement system (part of the immune system) becomes overactive. There are different types of C3G. Understanding the differences can help you better understand your symptoms, treatment options, and outlook.

In this article, we’ll review how the type of C3G can impact who’s typically affected, the progression of kidney disease, and treatment options.

Types of C3 Glomerulopathy

C3G is an umbrella term that includes two different types:

• Dense deposit disease — Previously known as membranoproliferative glomerulonephritis (MPGN) type 2
• C3 glomerulonephritis (C3GN) — Previously known as MPGN type 1 or 3

In both types of C3G, the complement system gets out of control and is more active than it should be. Normally, the complement system helps your immune system fight infections. In people with C3G, a key complement protein called C3 is broken down into smaller pieces that can build up in the kidneys. This glitch in the complement system can cause damage to the kidney’s filtering units, called glomeruli.

Although drusen and vision problems can happen in people with C3GN, these symptoms are more commonly seen in people with DDD.

Immune complex membranoproliferative glomerulonephritis (IC-MPGN) is another related type of kidney disease that also affects the glomeruli.

When the glomeruli become damaged, they aren’t as good at filtering the blood to make urine. Without proper treatment, continued kidney damage can lead to worsening kidney function and kidney failure.

Although DDD and C3GN are both caused by problems with the complement system, they can affect people in different ways.

Dense Deposit Disease Usually Affects Younger People

About 2 to 3 people out of every 1 million people in the U.S. are diagnosed with a type of C3G. It’s estimated that fewer than 5,000 people in the U.S. are living with DDD.

Anyone can develop DDD or C3GN at any age. However, people who develop DDD tend to be younger than those who have C3GN. Overall, DDD typically develops in children and young adults. In contrast, C3GN usually affects adults older than 30 years.

People With Dense Deposit Disease May Experience Different Symptoms

The symptoms of all types of C3G are typically very similar and may include:

• Hematuria (blood in the urine)
• Proteinuria (high levels of protein in the urine)
• Less frequent urination than usual
• Hypertension (high blood pressure)
• Edema (swelling)
• Loss of appetite

While the symptoms of both types of C3G are similar, people with DDD tend to have worse kidney function when they’re first diagnosed. Additionally, about half of people with DDD have nephrotic syndrome at diagnosis, which happens when the kidneys lose an excessive amount of protein in the urine.

Dense deposit disease (DDD) is a type of C3 glomerulopathy (C3G) — a rare disease that happens when the complement system (part of the immune system) becomes overactive.

DDD is also more commonly associated with symptoms that affect other parts of the body, including vision problems and lipodystrophy (unusual fat loss or buildup in different parts of the body).

Vision Problems in DDD

People with DDD can also develop deposits in their eyes that can affect their vision. These deposits are called drusen. The drusen can build up in the retina — the tissue at the back of the eye that detects light. Drusen can form in a part of the retina called Bruch’s membrane, which is similar to the part of the kidney that’s affected in DDD.

When drusen develop on the retina, they can cause additional symptoms, such as:

• Difficulty seeing at night or in low light
• Vision loss
• Difficulty differentiating between colors

Although drusen and vision problems can happen in people with C3GN, these symptoms are more commonly seen in people with DDD.

Lipodystrophy in DDD

Lipodystrophy is a condition where the body loses fat tissue in certain areas. Some children with DDD can develop acquired partial lipodystrophy. This causes fat loss in the face, arms, or upper body. However, there may be excess fat stored around the stomach, buttocks, and legs.

Acquired partial lipodystrophy isn’t common in C3GN.

Dense Deposit Disease and C3 Glomerulonephritis Look Different Under a Microscope

Since the symptoms of DDD and C3GN are often very similar, doctors need to order specific tests to tell the difference. A kidney biopsy is one of the key tests to help make a diagnosis. In a kidney biopsy, a kidney specialist or a radiologist will take a small sample of kidney tissue to examine using electron microscopy (a special type of microscope technique). Under this microscope, DDD usually shows C3 deposits that look like thick ribbons. In C3GN, the C3 deposits look more scattered and grainy instead of ribbonlike.

Dense Deposit Disease Often Progresses Rapidly

End-stage renal disease — also called ESRD or kidney failure — is common in people with any type of C3G. However, the prognosis (outlook) for people with DDD is often worse because this condition tends to progress more rapidly than C3GN. About half of people with DDD progress to end-stage kidney disease within 10 years of their diagnosis.

Research has shown how this faster progression affects kidney survival. In a 2012 study of 134 people with C3G, no adult with DDD was still alive with a functioning kidney after 10 years. In contrast, about 82 percent of adults with C3GN still had a functioning kidney after 10 years. Therefore, this study indicates a worse outcome in adults with DDD as compared to children with DDD. However, other scientists did not report similar results, and more studies are needed to confirm the differences in outcomes in adults versus children with DDD.

Treatments for Dense Deposit Disease and C3 Glomerulonephritis

Both types of C3G are treated by a kidney specialist called a nephrologist. Treatment aims to slow the progression of the disease and help manage the symptoms.

DDD and C3GN are treated in similar ways. Treatment often includes:

• Blood pressure medicines (such as ACE inhibitors or ARBs) to lower pressure in the kidneys and reduce protein in the urine
• Cholesterol-lowering medicines to help protect the heart
• Immunosuppressive medicines (including corticosteroids) to calm the immune system
• Complement inhibitors, which target different parts of the complement system
• Plasma exchange (plasmapheresis) to remove harmful immune proteins from the blood
• Healthy diet and lifestyle changes

People with C3G who develop kidney failure may need additional treatments, including dialysis or a kidney transplant. Your healthcare team can talk you through the best treatment options based on the type of C3G you have, your symptoms, and your overall health. Talk to your doctor about how DDD or C3GN can affect your symptoms, treatment options, and prognosis.

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