Rapidly Progressive Glomerulonephritis

Crescentic glomerulonephritis, RPGN

Rapidly progressive glomerulonephritis is a serious kidney condition that can damage your kidneys in just days to weeks. Without early diagnosis and treatment, it can lead to permanent kidney failure.

Table of contents

• What is Rapidly Progressive Glomerulonephritis?
• Types and Causes
• Signs and Symptoms
• How Doctors Diagnose RPGN
• Treatment Options
• What to Expect

What is Rapidly Progressive Glomerulonephritis?

Rapidly progressive glomerulonephritis (RPGN) is a condition where your kidneys suddenly lose their ability to filter waste from your blood.^[1] This can happen over a very short time—anywhere from a few days to a few months.^[3]

Your kidneys contain tiny filters called glomeruli (pronounced gloe-MER-u-lie). These structures remove waste and extra fluid from your bloodstream to make urine. In RPGN, these filters become severely damaged and inflamed.^[1] When doctors examine kidney tissue under a microscope, they see characteristic crescent-shaped scars forming in at least half of the glomeruli. Because of these crescents, this condition is also called crescentic glomerulonephritis.^[1]

• Kidneys
• Glomeruli
• Bowman’s space
• Glomerular basement membrane

If left untreated, RPGN progresses to complete kidney failure within weeks to months.^[2] The condition is relatively uncommon, and how often it occurs depends on what causes the underlying kidney inflammation.^[2] For example, among people with poststreptococcal glomerulonephritis—a kidney inflammation that follows a strep infection—approximately 12% will develop RPGN.^[2]

Types and Causes

Doctors classify RPGN into different types based on what they see when they examine kidney tissue and test your blood.^[1] Understanding the type helps guide treatment.

Type I: Anti-Glomerular Basement Membrane (Anti-GBM) Disease

This type accounts for about 10% to 20% of RPGN cases.^[2] It happens when your immune system creates antibodies that attack a specific protein in your kidney filters. These antibodies stick to the glomerular basement membrane, which is part of the kidney’s filtering system.^[4]

Sometimes these same antibodies also attack lung tissue, causing bleeding in the lungs. When both the lungs and kidneys are affected, doctors call this Goodpasture syndrome.^[2] This may develop after respiratory exposures like cigarette smoke or viral infections expose certain proteins that trigger antibody formation.^[2]

Type II: Immune Complex-Mediated Disease

This is the most common type, responsible for about 40% to 50% of RPGN cases.^[2] In this type, clusters of immune proteins deposit in the kidney filters, causing inflammation and damage.^[1]

Many different conditions can cause this type of RPGN. Infections are a common trigger, including strep throat, infective endocarditis (a heart valve infection), and infections with viruses like hepatitis B.^[2] Autoimmune diseases can also cause immune complex deposits. These include systemic lupus erythematosus (lupus), IgA nephropathy, and conditions involving abnormal immune proteins like cryoglobulinemia.^[2]

Type III: Pauci-Immune Disease

This type accounts for 30% to 50% of adult RPGN cases and is the most common form in adults.^[3] The name “pauci-immune” means “few immune deposits”—when doctors examine kidney tissue, they find little or no immune protein deposits.^[1]

Most people with this type (80% to 90%) have antibodies in their blood called antineutrophil cytoplasmic antibodies (ANCA).^[3] These antibodies cause inflammation of small blood vessels throughout the body, a condition called vasculitis. Diseases in this category include granulomatosis with polyangiitis (formerly called Wegener’s disease), microscopic polyangiitis, and kidney-limited disease where only the kidneys are affected.^[3]

Type IV: Double-Antibody Positive

In rare cases, people have both anti-GBM antibodies and ANCA antibodies at the same time.^[2] Having both types of antibodies affects how the disease behaves and how doctors treat it.

Signs and Symptoms

Many people with RPGN don’t experience obvious symptoms at first.^[1] Sometimes the first sign of a problem comes from routine urine tests ordered for other reasons.

Early Warning Signs

More than 90% of people with ANCA-associated types of RPGN first experience flu-like symptoms.^[3] These may include general feelings of illness, fever, joint pain, muscle aches, loss of appetite, and weight loss.^[3]

Kidney-Related Symptoms

As the condition affects the kidneys, you may notice:

• Blood in the urine, which may make it look brown, pink, or red^[1]
• Foamy or bubbly-looking urine^[1]
• Swelling in your legs, ankles, or face^[1]
• Urinating less often than usual^[1]
• High blood pressure^[1]

When Other Organs Are Affected

If RPGN is part of a condition affecting blood vessels throughout your body (vasculitis), you might also experience:

• Abdominal pain^[3]
• Painful skin nodules or ulcers^[3]
• Joint pain that moves from one joint to another^[3]
• Sinus problems, cough, or coughing up blood (when lungs are involved)^[3]
• Eye problems^[3]
• Rash^[1]

If you have any of these symptoms, contact a healthcare provider. Many other health conditions can cause similar symptoms, so proper testing is needed to determine the cause.^[1]

How Doctors Diagnose RPGN

Early diagnosis is crucial to prevent permanent kidney damage.^[1] Doctors use several tests to diagnose RPGN and determine its type.

Urine Tests

A urinalysis examines your urine for signs of kidney problems. In RPGN, doctors typically find blood in the urine, unusual-looking red blood cells, clumps of red blood cells called casts, and excess protein.^[1] These findings suggest active kidney inflammation.

Blood Tests

Blood tests check how well your kidneys are filtering waste. Elevated levels of waste products like creatinine and urea indicate reduced kidney function.^[4]

Special blood tests look for specific antibodies that indicate the type of RPGN:

• Anti-GBM antibodies suggest Type I RPGN^[4]
• ANCA antibodies suggest Type III (pauci-immune) disease^[4]
• Antinuclear antibodies (ANA) may support a diagnosis of lupus and Type II RPGN^[4]

Kidney Biopsy

A kidney biopsy is often needed to confirm the diagnosis. During this procedure, doctors remove a small sample of kidney tissue to examine under a microscope.^[4] The biopsy shows the characteristic crescent-shaped scars and helps identify the specific type of RPGN based on the pattern of immune protein deposits.^[1]

Imaging Tests

An ultrasound of the abdomen may be performed to examine the kidneys and rule out other causes of kidney problems.^[4]

Treatment Options

Treatment for RPGN aims to stop further kidney damage, preserve remaining kidney function, and manage the underlying cause. The sooner treatment begins, the better the outcome.^[1] The only predictor of kidney survival is how much kidney function remains when treatment starts, making early diagnosis critical.^[9]

Medications

Most people with RPGN receive treatment with powerful medications that suppress the immune system.

Corticosteroids are the foundation of treatment. Doctors often start with high doses given through a vein (intravenously), then switch to pills taken by mouth.^[9] A typical regimen might include methylprednisolone intravenously for three days, followed by oral prednisone that is gradually reduced over several months.^[9]

Additional immunosuppressive medications are usually combined with steroids. Cyclophosphamide is commonly used and can be given either through a vein or as pills.^[9] Treatment with steroids alone results in three times more disease relapses compared to combination therapy.^[9]

Other medications that may be used include:

• Rituximab, a medication that targets specific immune cells^[9]
• Azathioprine, which may replace cyclophosphamide after initial treatment^[9]
• Avacopan, a newer medication approved as additional therapy^[9]

Plasmapheresis

Plasmapheresis (also called plasma exchange) is a procedure that filters harmful antibodies from the blood. It may be added to medication treatment for people with severe kidney failure or for those whose disease worsens despite treatment.^[9] This treatment is particularly important for people with anti-GBM disease.^[2]

Dialysis and Kidney Transplant

Even if kidney failure requires dialysis when RPGN is diagnosed, treatment should still be started. Many people can be removed from dialysis for extended periods—18 months to 2 years or more—if treatment is successful.^[9]

For those who develop permanent kidney failure, options include long-term dialysis or kidney transplant.^[1] A multidisciplinary team including kidney specialists (nephrologists), intensive care nurses, and pharmacists work together to provide comprehensive care.^[1]

What to Expect

The outcome for people with RPGN varies widely and depends on several factors, including how much kidney function remains when treatment begins, the type of RPGN, and how quickly treatment is started.^[1]

Early diagnosis and prompt treatment are crucial for the best possible outcome.^[1] Some people recover significant kidney function with treatment, while others may progress to permanent kidney failure requiring lifelong dialysis or transplant.

Without treatment, RPGN progresses to complete kidney failure within weeks to months.^[2] Even with treatment, in rare cases—about 1% of children and 10% of adults with acute kidney inflammation—the disease can evolve into RPGN and cause rapid destruction of kidney filters.^[4]

People who recover from RPGN need ongoing monitoring to watch for disease recurrence and to manage any remaining kidney problems. Regular follow-up with healthcare providers is essential for long-term health.^[1]