Membranoproliferative Glomerulonephritis

Membranoproliferative GN, MPGN, Mesangiocapillary glomerulonephritis, Lobular glomerulonephritis

Membranoproliferative glomerulonephritis is an uncommon kidney disorder that involves inflammation and damage to the tiny filters in your kidneys, potentially leading to serious kidney problems and requiring ongoing medical care.

Table of contents

• What is membranoproliferative glomerulonephritis?
• What causes this condition?
• Who is affected?
• What symptoms might you experience?
• How is the condition diagnosed?
• How is it treated?
• What is the outlook?
• Possible complications

What is membranoproliferative glomerulonephritis?

Membranoproliferative glomerulonephritis (MPGN) is a kidney disorder that involves inflammation of the glomeruli, which are the tiny filters in the kidneys that help remove waste and extra fluids from the blood to form urine.^[1] This condition causes changes to the kidney cells that can seriously affect how well your kidneys work.

In MPGN, the glomeruli become damaged through a specific pattern of injury. Under a microscope, doctors can see that cells in the kidney are multiplying abnormally and that the walls of the tiny blood vessels in the kidney are getting thicker.^[4] These changes are caused by deposits of antibodies or other substances that build up in a part of the kidneys called the glomerular basement membrane. This membrane normally helps filter waste products, but when it becomes damaged, it cannot work properly.^[1]

The damage to this filtering membrane affects the kidney’s ability to create urine normally. Blood and protein may leak into the urine, and if enough protein leaks out, fluid can escape from blood vessels into body tissues, causing swelling. Waste products that should be removed may also build up in the blood.^[1]

What causes this condition?

MPGN can be classified as either primary (idiopathic) or secondary. In primary MPGN, the cause is unknown. However, most cases of MPGN are secondary, meaning they are caused by another underlying condition.^[4] Secondary forms are more common than primary forms and tend to affect adults, while primary forms more often affect children and young adults.^[5]

Based on how the disease develops, doctors now classify MPGN into three main types:^[4]

• Immunoglobulin or immune complex-mediated MPGN
• Complement-mediated MPGN
• MPGN without immunoglobulin or complement deposition

The immunoglobulin or immune complex-mediated type is caused by chronic exposure to antigens or circulating immune complexes. This type most commonly occurs secondary to several conditions including:^[4]

• Autoimmune diseases such as systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, or scleroderma
• Chronic infections such as hepatitis B, hepatitis C, HIV infection, bacterial endocarditis, or malaria
• Blood cancers such as leukemia, lymphoma, or multiple myeloma
• Other conditions including sarcoidosis or chronic liver disease

The complement-mediated type is caused by problems with the body’s complement system, which is part of the immune system. In this type, there is persistent activation of one of the complement pathways, leading to deposits of complement products in the kidney.^[4]

A low level of complement proteins in the blood (hypocomplementemia) is a characteristic finding in approximately 75% of patients with MPGN.^[2] Some cases appear to run in families, suggesting that genetic factors may play a role in at least some instances.^[4]

Who is affected?

MPGN is an uncommon cause of chronic kidney inflammation that occurs primarily in children and young adults.^[2] Primary forms affect children, particularly between 2 and 15 years of age, and account for less than 10% of cases of nephrotic syndrome (a kidney disorder characterized by heavy protein loss in urine) in children.^[4] Secondary forms tend to affect adults over age 30.^[5] Men and women are affected equally.^[5]

What symptoms might you experience?

The clinical presentation of MPGN can vary widely. Some patients may have few symptoms, while others develop more severe problems.^[4] Many people present with a mix of both nephritic and nephrotic features.^[4]

Symptoms may include any of the following:^[1]

• Blood in the urine
• Cloudy urine
• Dark-colored urine (smoke, cola, or tea colored)
• Decrease in the amount of urine
• Swelling of any part of the body, often in the legs
• Changes in mental status such as decreased alertness or decreased concentration

You may also have high blood pressure. When your healthcare provider examines you, they may find signs of too much fluid in the body, such as swelling and abnormal sounds when listening to your heart and lungs with a stethoscope.^[1]

The urine sediment may reveal hematuria (blood in the urine with abnormal red blood cells) and proteinuria (protein in the urine). The degree of protein in the urine is variable. The blood levels of waste products (serum creatinine) may be normal or elevated.^[5]

In patients with dense deposit disease, a subtype of complement-mediated MPGN, there is a greater incidence of eye abnormalities that can ultimately impair vision.^[5]

How is the condition diagnosed?

The healthcare provider will examine you and ask about your symptoms. Several tests help confirm the diagnosis.^[1]

Initial blood and urine tests include:^[1]

• Blood urea nitrogen (BUN) and creatinine blood test to check kidney function
• Blood complement levels
• Urinalysis
• Urine protein measurement

Low complement levels in the blood provide supportive evidence for the diagnosis. In immunoglobulin or immune complex-mediated MPGN, C3 is normal or mildly decreased, and C4 is typically decreased. In complement-mediated MPGN, C3 is decreased but C4 is normal.^[5]

The definitive diagnosis is made by kidney biopsy, which involves taking a small sample of kidney tissue and examining it under a microscope.^[1] The pattern of immunoglobulin and complement deposits seen on special microscopy techniques helps classify the type of MPGN.^[5]

Additional tests are done to help identify underlying causes of secondary MPGN. These may include tests for autoimmune diseases, infections such as hepatitis B and C, and blood cancers.^[5]

How is it treated?

Treatment depends on the symptoms and the type of MPGN. The goals of treatment are to reduce symptoms, prevent complications, and slow the progression of the disorder.^[1]

When immune complex-mediated MPGN is identified, the initial approach to treatment should focus on treating the underlying cause, when present.^[7] For secondary forms, treating the underlying condition is essential. For example, if the MPGN is caused by hepatitis C, treating the hepatitis may help the kidney condition.^[7]

For patients with idiopathic (primary) MPGN, treatment may be supportive or include medications to suppress the immune system. The specific approach depends on several factors including the level of protein in the urine, kidney function, and the presence of active disease on biopsy.^[7]

General supportive measures include:

• Changes in diet, which may include limiting sodium, fluids, or protein to help control high blood pressure, swelling, and the buildup of waste products in the blood^[1]
• Blood pressure medicines, particularly ACE inhibitors or angiotensin receptor blockers, which can help reduce protein in the urine^[7]
• Diuretics to control swelling^[1]
• Medications to control high cholesterol^[7]

For patients with more severe disease, medications that may be prescribed include:^[1]

• Corticosteroids (steroids) such as prednisone
• Immunosuppressive drugs such as cyclophosphamide, mycophenolate mofetil, or cyclosporine
• Antiplatelet drugs such as dipyridamole, with or without aspirin
• Complement inhibitors such as eculizumab for refractory cases of complement-mediated disease

For patients with moderate-to-severe C3 glomerulonephritis without a blood cancer causing abnormal proteins, treatment with mycophenolate mofetil plus steroids is recommended initially. For cases that don’t respond, eculizumab should be considered.^[7]

Long-term steroid treatment seems to be effective in children with heavy protein loss in the urine.^[6] Treatment is generally more effective in children than in adults.^[1]

If kidney function continues to decline despite treatment, dialysis or kidney transplant may eventually be needed.^[1]

What is the outlook?

The outlook for MPGN varies depending on several factors. The disorder often slowly gets worse and can eventually result in chronic kidney failure.^[1]

About one-third of patients experience spontaneous remission, meaning the protein leakage into the urine goes away by itself. In another third of patients, the amount of protein leaking in the urine reduces but doesn’t go away completely. The remaining third of patients progress to kidney failure.^[16]

Half of people with this condition develop long-term (chronic) kidney failure within 10 years. This is more likely in those who have higher levels of protein in their urine.^[1]

MPGN tends to recur after kidney transplantation, especially the dense deposit disease type.^[6] The rate of recurrence varies depending on the type and mechanism of injury.^[2]

Possible complications

Complications that may result from MPGN include:^[1]

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

In very severe cases of nephrotic syndrome, there is an increased risk of developing blood clots, infections, and high cholesterol levels.^[16]

Contact your healthcare provider if you have symptoms of this condition, if your symptoms get worse or do not go away, or if you develop new symptoms, including decreased urine output.^[1]

Preventing infections such as hepatitis or managing diseases such as lupus may help prevent secondary MPGN.^[1]

• Kidneys
• Glomeruli
• Glomerular basement membrane