Dense deposit disease (DDD) is an extremely rare kidney disease affecting fewer than 5,000 people in the United States. DDD damages the kidneys’ filters over time, and many people eventually develop kidney failure. When living with a rare disease like DDD, it’s vital to learn as much as you can to lead a healthier life.

This article will cover five facts to know about DDD. It will touch on the disease’s causes, symptoms, and how doctors diagnose it. We’ll also discuss how DDD treatments focus on slowing kidney damage and controlling symptoms.

1. DDD Is a Rare Disease Affecting the Kidneys’ Filters

DDD is a rare kidney disease that falls under the umbrella of complement 3 glomerulopathy (C3G). The other type of C3G is called C3 glomerulonephritis (C3GN). Both types of C3G affect the kidneys’ glomeruli. Glomeruli are delicate filters that remove waste and toxins from the blood to make urine. Doctors tell DDD apart from C3GN by how kidney tissue looks under a microscope.

People with DDD have an overactive complement system. The complement system is the first line of defense in your immune system. Under normal circumstances, the complement system stays inactive until it’s needed. Specific proteins act like “brakes” that keep it under control. People with DDD don’t have these brakes, which leads to overactivation of the complement system.

Normally, when the complement system is activated to destroy harmful germs, the complement protein 3 (C3) breaks into smaller fragments. In DDD, overactivation causes too many of these small fragments to stick in the glomeruli. This creates inflammation that damages the filters and impacts their function.

2. DDD Has Autoimmune and Genetic Causes

Doctors and researchers have found that DDD has two main causes. It can be caused by immune system proteins that target the complement system, or it can be caused by genetic mutations (changes) that affect complement proteins. Both causes take away the “brakes” and eventually lead to kidney damage.

Nephritic Factors in DDD

Some people with DDD have abnormal antibodies called nephritic factors (NeFs). Antibodies are immune system proteins that protect you from infections. Some antibodies, called autoantibodies, mistakenly attack you instead of harmful germs.

NeFs are autoantibodies that target complement factor H (CFH). Under normal circumstances, factor H keeps the complement system turned off. NeFs stop factor H from doing its job, so the complement system turns on when it’s not needed. This sets off reactions that overactivate the system and damage the kidneys.

Research shows that around 80 percent of DDD subjects have C3 nephritic factor (C3NeF) activity.

Genetic Changes in DDD

Genes provide instructions for making proteins, like a recipe in a cookbook. Mutations in genes cause the body to produce faulty proteins that don’t work like they should. Studies have found that mutations in the CFH gene also lead to complement system dysregulation. Some cases of DDD develop from CFH gene mutations.

3. People With DDD Can Have Body-Wide Symptoms

DDD symptoms tend to start earlier in life, usually when people are teenagers. However, some people may not notice any signs until they’re adults.

Everyone with DDD has blood or protein in their urine. Healthy glomeruli normally stop large molecules — like proteins and blood cells — from getting into urine. Some people have dark, foamy urine as a sign of proteinuria or protein in their urine. Red, brown, or pink pee may be due to hematuria or blood in the urine.

Since more protein leaks into urine than normal, it throws off the body’s fluid balance. Low protein levels force fluid out of the bloodstream and into nearby tissues. This causes swelling or edema. Signs of DDD include swelling in the ankles and feet.

Another symptom of kidney disease is hypertension (high blood pressure). Around half of people with DDD have high blood pressure. Hypertension is common in kidney diseases because the kidneys play a key role in controlling blood pressure levels. Damaged kidneys can’t remove extra fluid, so it builds up in the body. This puts added pressure on the blood vessels.

People with DDD can also develop drusen (clumps of proteins and fats) in their eyes. These deposits form in the retina (the light-sensitive tissue in the center of the eye). Most cases of drusen don’t cause any symptoms. Eye doctors usually find them during routine eye exams.

Partial lipodystrophy refers to an abnormal distribution of fat tissue in the body. You may be at risk for this condition if you have DDD. Some people develop partial lipodystrophy before or after their DDD diagnosis. The fat loss may affect the abdomen, upper body, face, and arms. Researchers think partial lipodystrophy is due to the complement system destroying fat cells.

4. Doctors Use Blood Tests, Urine Tests, and Powerful Microscopes To Diagnose DDD

If you begin experiencing symptoms of DDD, make an appointment with your doctor. They’ll likely refer you to a nephrologist or kidney specialist. Nephrologists are specially trained to diagnose and treat rare kidney diseases like DDD.

Blood and Urine Tests

Blood and urine tests check for abnormalities associated with DDD. Urine tests look for blood cells and abnormally high protein levels in urine.

Using a small blood sample, doctors can measure your complement protein levels. Low C3 and normal C4 protein levels are key to diagnosing DDD. Blood tests check for waste products that accumulate in the body, such as creatinine and urea, as well as any imbalances in electrolyte levels. Blood tests also check your estimated glomerular filtration rate (eGFR). This is a measure of how well your kidneys filter blood, and the values indicate the severity of kidney damage.

Kidney Biopsy and Imaging

If urine tests show that you have proteinuria and hematuria, your doctor will order more testing. Kidney biopsies are a key part of diagnosing C3G. Your nephrologist or a radiologist will use a thin needle to take a small tissue sample from your kidney. The sample is sent to a lab for closer inspection.

Immunofluorescence uses special dyes that attach to specific proteins. When looked at under a special microscope, tissue specialists can see where the proteins are. Pictures of DDD using immunofluorescence show deposits or clumps of C3 proteins stuck in the kidneys.

Electron microscopy uses powerful microscopes to magnify images thousands of times. Tissue samples from people with DDD show sausage-shaped or ribbonlike C3 deposits. These pictures help doctors tell the difference between DDD and C3GN. C3 deposits in C3GN usually form in different parts of the kidney compared to DDD.

5. The First Medication for DDD Was Approved in 2025

Unfortunately, around 50 percent of people with DDD develop kidney failure within 10 years of their diagnosis. After 20 years, that number increases to 85 percent. Working closely with your nephrologist and following your treatment plan can help slow DDD progression and prolong kidney failure.

Until recently, there weren’t any DDD treatments approved by the U.S. Food and Drug Administration (FDA). In March 2025, the U.S. Food and Drug Administration (FDA) approved the complement inhibitor iptacopan (Fabhalta) to treat C3G. Iptacopan is the first drug approved by the FDA for this condition. It is also approved for the rare kidney disease immunoglobulin A nephropathy (IgAN) and for a rare blood disorder called paroxysmal nocturnal hemoglobinuria. Complement inhibitors block specific parts of the complement system.

Other treatments for DDD focus on treating symptoms like high blood pressure and proteinuria. If you’ve been diagnosed with DDD, the first treatment you may have been given is a blood pressure medication. These drugs lower the amount of protein lost in your urine. Examples include:

• Angiotensin converting enzyme (ACE) inhibitors
• Angiotensin II receptor blockers (ARBs)

Corticosteroids (steroids) and immunosuppressive drugs help calm inflammation to protect the kidneys. The exact treatment your doctor prescribes will depend on how severe your disease is. An example of an immunosuppressant used for DDD is mycophenolate mofetil (MMF). Your doctor may prescribe MMF alone or together with a steroid.

In people who develop kidney failure, dialysis and kidney transplants are an option. If you have a kidney transplant, there’s a chance your DDD will affect the new kidney. Around half of transplants in people with DDD eventually fail within 10 years.

Talk With Others Who Understand

On MyKidneyDiseaseTeam, people with kidney disease and their loved ones come together to ask questions, give advice, and share their stories with others who understand life with kidney disease.

Are you living with dense deposit disease? What symptoms did you experience before your diagnosis? What treatments help you manage your disease? Share your story in the comments below, or start a conversation by posting on your Activities page.