Definition

Membranoproliferative glomerulonephritis (MPGN) is a kidney disease characterized by inflammation and changes in the glomeruli, which are structures in the kidney responsible for filtering fluid and waste substances from the blood to form urine.

Various diseases can impact kidney function by attacking and damaging the glomeruli, collectively known as glomerular disease. MPGN is one such glomerular disease.

MPGN manifests in three forms based on the mechanism of kidney damage and the part of the glomerulus affected. Each type is further divided into primary and secondary forms. These forms are MPGN Type I, II, and III. While Type I is the most common (making up approximately 80% of all MPGN cases), Types II and III are rarer but often lead to more severe diseases.

Causes

Membranoproliferative glomerulonephritis (MPGN) is a form of glomerulonephritis caused by an abnormal immune system response, where the immune system mistakenly attacks healthy cells in the kidneys, leading to damage in the glomeruli.

The immune system produces proteins known as antibodies to target harmful substances in the body, called antigens. When antigens combine with antibodies, they form immune complexes. In MPGN, these immune complexes accumulate in a part of the kidney known as the glomerular basement membrane, which filters waste substances and excess fluid from the blood.

Damage to this membrane impairs the kidney's ability to filter urine normally, leading to blood and protein leakage into the urine. If a significant amount of protein leaks into the urine, fluid can escape from blood vessels into body tissues, causing swelling. Waste nitrogen substances may also accumulate in the blood, known as azotemia.

MPGN Type I, which has an unknown cause, is less common. Type I often occurs secondary to other conditions, such as:

• Autoimmune diseases (lupus, scleroderma, Sjörgen's syndrome, sarcoidosis)
• Cancer (chronic lymphocytic leukemia, lymphoma, melanoma)
• Chronic infections (hepatitis B, hepatitis C, bacterial endocarditis, HIV infection, internal organ abscess, heart shunt infection, malaria)
• Other diseases (partial lipodystrophy, C2 or C3 deficiency, sarcoidosis, thrombotic microangiopathy).

Risk factor

MPGN can occur in individuals of any age but is more common in children than in adults, with an estimated incidence of 2-3 cases per 1,000,000 people.

Primary MPGN primarily affects children and young adults aged 8 to 30, while secondary MPGN tends to affect adults over 30.

The condition affects males and females equally.

A family history of MPGN increases an individual's risk of developing the disease.

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Symptoms

The symptoms of MPGN include:

• Presence of blood in the urine: Glomerular diseases can cause blood leakage, resulting in a pink or light brown appearance.
• Changes in mental status, such as decreased consciousness and/or concentration.
• Cloudy or foamy urine: Glomerular diseases can lead to protein leakage into the urine, causing it to become foamy.
• Dark urine (cola- or tea-colored).
• Decreased urine volume.
• Swelling in parts of the body: Glomerular diseases can cause fluid retention, resulting in swelling in areas such as the hands, ankles, and around the eyes.
• Nephrotic syndrome: This collection of symptoms affecting the kidneys includes:
• Swelling in body parts such as the limbs, ankles, or around the eyes.
• Presence of a large amount of protein in the urine.
• Protein deficiency in the blood.
• Increased levels of fats in the blood (high cholesterol).
• High blood pressure.

Patients with MPGN type II are more likely to experience eye abnormalities that can lead to vision disturbances.

Diagnosis

To diagnose MPGN, the doctor will inquire about your symptoms and conduct a physical examination. During the examination, the doctor will look for signs of fluid retention in the body, such as swelling, often in the legs, and abnormal heart and lung sounds heard through a stethoscope. Additionally, they will check for high blood pressure.

To confirm the diagnosis of MPGN, the following tests may be conducted:

• Complete blood count: This test will reveal protein, cholesterol, and waste products such as BUN and creatinine levels in the blood.
• Urine test: This test helps detect the presence of protein and blood in the urine.
• Glomerular filtration rate (GFR): Blood tests assess how well the kidneys filter waste products from the body.
• Kidney biopsy: This examination is the most reliable method to confirm the presence of MPGN. A small portion of the kidney is extracted using a special needle and examined under a microscope. The location of immune complex deposits helps distinguish between the three types of MPGN. Identifying the type of disease aids the doctor in selecting the most appropriate therapy, making this examination crucial.
• Genetic testing: This examination can identify if MPGN is caused by genetic abnormalities inherited from the family.
• Blood complement profile test: Complements are products of the immune system. This test can support the diagnosis and determine the type of MPGN.
• Serological tests detect antibodies in diseases such as lupus, hepatitis B, and hepatitis C. The aim is to investigate the causes of secondary type I MPGN.

Management

Treatment and therapy for MPGN depend on the symptoms and aim to alleviate symptoms, prevent complications, and slow disease progression. Before establishing a treatment plan, the doctor will try to identify the underlying cause of the MPGN. If MPGN is not caused by other conditions, such as hepatitis C, the treatment approach will differ. 

Therapy with medications can help slow down disease progression and manage symptoms such as high blood pressure, protein leakage in the urine, and swelling. Medications that your doctor may prescribe include:

• Blood pressure-lowering medications: These help control blood pressure and reduce protein loss.
• Dipyridamole
• aspirin
• Diuretics
• Steroids and immunosuppressive drugs, such as cyclophosphamide: These medications suppress immune system activity to prevent further damage to the glomeruli.

In addition to medication, dietary adjustments may be necessary. Your doctor may recommend limiting sodium, fluids, or protein intake to help control blood pressure, swelling, and the buildup of waste products in the blood.

If kidney failure occurs, dialysis or kidney transplantation may be necessary to manage the condition.

Complications

MPGN often involves a gradual worsening and can eventually lead to kidney failure. Approximately half of MPGN patients develop chronic kidney failure within 10 years, especially those with higher levels of protein leakage in the urine.

Common complications of MPGN include:

• Acute nephritic syndrome
• Acute kidney failure
• Chronic kidney disease

Prevention

Preventing infections such as hepatitis and effectively managing diseases like lupus can reduce the risk of developing MPGN.

When to see a doctor?

You are advised to consult a doctor if:

• You experience symptoms of GNMP
• Your symptoms do not improve or worsen
• You develop new symptoms, including decreased urine volume

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