Introduction

Fibrillary glomerulonephritis is a rare kidney disease that affects the small filtering units inside the kidneys, called glomeruli. Small proteins, known as fibrils, are deposited in the glomeruli, stopping the kidneys from working as they should. Over time, this can lead to the loss of kidney function, and the kidneys may begin to fail. In kidney failure, kidneys become unable to clean the blood, filter out waste, produce hormones and regulate salt and water balances; this is usually treated with dialysis, or with a kidney transplant. 

The kidneys

The kidneys are two bean-shaped organs that are situated in the back, just below the ribcage.¹ They have a wide range of important roles in the body, including:

• Filtering the blood
• Produce urine
• Removing toxins and waste products
• Salt and water balance
• Regulating blood pressure
• Produce hormones

Each kidney consists of around one million filtering units, called nephrons. One key part of the nephron is the glomerulus, which is a complex collection of small blood vessels that help to filter and clean the blood. The glomerulus is surrounded by a glomerular basement membrane, which also helps to filter substances out of the blood, and provide structural support to the glomerulus. 

The glomerulus and glomerular basement membrane are the key parts of the kidney that are damaged in fibrillary glomerulonephritis.

Proteinuria

Proteinuria is the presence of abnormally high amounts of protein in the urine. Small molecules, such as sugars, salts and water, can all pass through the glomeruli (filtering units) in the kidneys. Red blood cells, proteins, and other larger molecules cannot be filtered through the glomeruli as they are too big. When the kidneys become damaged, the glomeruli can become leaky, and larger molecules can pass through into the urine. This can lead to abnormally high levels of protein in the urine, which is called ‘proteinuria’. Healthy urine usually contains very few proteins; however, if your kidneys are damaged, your urine may contain more protein than normal.

Proteinuria can be a sign of fibrillary glomerulonephritis, and other kidney diseases - it is a key marker of overall kidney health and function. 

What is fibrillary glomerulonephritis?

Fibrillary glomerulonephritis develops when fibrils (unusual proteins produced by the body) are deposited in the kidneys. These fibrils become trapped in the layers of the small filters (glomeruli) in the kidney, disrupting filtration and causing swelling. This damages the glomeruli and the glomerular basement membrane. Over time, the swelling and damage progresses, and the glomeruli become irreversibly damaged. This damage is then replaced by scar tissue. As more and more glomeruli become damaged and more scar tissue develops, kidney function begins to decline.²

Causes of fibrillary glomerulonephritis

Currently, the causes of fibrillary glomerulonephritis are unknown. However, there are a number of conditions that fibrillary glomerulonephritis is associated with, including:

• Immunological conditions
  • Such as lupus, where the immune system is dysfunctional⁴
• Infections
  • Such as Hepatitis C, where the immune system is activated for a long period of time⁴
• Cancer
  • Both current and in the past⁴ 
• High blood pressure⁴
• Diabetes⁴

Fibrillary glomerulonephritis vs. renal amyloidosis

There is a very similar condition, called renal amyloidosis, where amyloid proteins are deposited in the kidneys and cause damage. Amyloid proteins are small, strong proteins that can cause damage in various areas of the body. Renal amyloidosis is different to fibrillary glomerulonephritis, as the proteins that are deposited are different; the proteins are different in size, and they look different when they are viewed under a microscope.³ The different features of the proteins when analysed in a laboratory can help scientists determine whether the kidney tissue has fibrillary glomerulonephritis, renal amyloidosis, or another condition.

Signs and symptoms of fibrillary glomerulonephritis

The signs of fibrillary glomerulonephritis are similar to the signs of many other kidney diseases. Early signs of fibrillary glomerulonephritis include blood in the urine (haematuria), a decline in kidney function, high blood pressure and protein in the urine (proteinuria). The build-up of fibril deposits disrupt the filtration barriers in the kidneys, causing the glomeruli to become leaky and allow proteins and blood to pass into the urine.² The leaky glomeruli lead to a decline in kidney function, and the extent of proteinuria is often used as a measure of this. 

• Blood in the urine (haematuria)⁴
  • The presence of blood can cause the urine to appear pink, red, or a dark brown colour. Sometimes, blood in the urine is not visible, and is only detectable on a urine dipstick test
• Protein in the urine (proteinuria)⁴
  • If there are high amounts of protein present, the urine may appear foamy. Proteinuria is usually diagnosed on a urine dipstick test
• High blood pressure⁴
• Reduced kidney function⁴

Although these are common clinical signs of fibrillary glomerulonephritis, patients may not experience symptoms until the condition is more advanced and kidney function has significantly reduced. Symptoms of kidney disease and poor kidney function can include nausea, fatigue, loss of appetite, itchy skin, swelling of the hands and feet, shortness of breath and difficulty sleeping.²

How is fibrillary glomerulonephritis diagnosed?

Your doctor may initially do some basic tests to check your kidney function. This may include taking a urine sample and doing blood tests. If these tests indicate that your kidneys may not be working as they should, your doctor may consider doing further investigations and referring to a specialist.

Fibrillary glomerulonephritis can only be diagnosed through a kidney biopsy.² A kidney biopsy is a small procedure, in which a small section of tissue is removed from the kidney and sent to a laboratory for further testing. The tissue is then analysed under a microscope, and scientists and doctors can then determine exactly what is causing the kidney disease, and decide on the best treatment. 

In fibrillary glomerulonephritis, the kidney tissue will contain deposits of fibrils in the glomerulus and the basement membrane. When a special dye, called Congo red stain, is applied to these fibrils, the result is negative.³ Congo red stain helps identify amyloid proteins, so a negative result indicates that the fibrils are not amyloid proteins- this helps doctors to rule out other conditions, such as renal amyloidosis.³ Other particular appearances when viewed under the microscope can help doctors and scientists to diagnose fibrillary glomerulonephritis, and rule out other similar conditions.

Treatment and management of fibrillary glomerulonephritis

Fibrillary glomerulonephritis is usually treated with medication to slow the decline in kidney function, and targeted therapies to control the immune system. 

General treatment of kidney disease

Medications to control and lower high blood pressure are commonly prescribed to people with fibrillary glomerulonephritis; these drugs help to protect the kidneys from damage, and they also help to reduce the amount of protein in the urine. Your doctor may also recommend dietary changes to help control your intake of certain salts and electrolytes, such as sodium. Following this diet and taking all prescribed medications helps manage kidney disease, and slow the rate of progression of the disease. 

Specific treatments for fibrillary glomerulonephritis

More specialist medications can be used to control the immune system in fibrillary glomerulonephritis. As the condition can be autoimmune in nature, drugs that suppress the immune system are often prescribed. 

Rituximab is one drug that has shown potential in trials as a treatment for fibrillary glomerulonephritis.⁶ Rituximab is a special protein, called a monoclonal antibody, that works by suppressing B cells. B cells are a type of white blood cell, and they are responsible for producing antibodies. In some forms of fibrillary glomerulonephritis, these antibodies can be the cause of the condition. Therefore, suppressing B cells can stop antibodies from being produced, and this can help to treat the condition.⁷

Steroids, such as prednisalone, are another type of medication that dampens and weakens the immune system, which can help to slow the progression of fibrillary glomerulonephritis⁵. 

Long-term outlook

In patients with fibrillary glomerulonephritis, regular follow-up with their healthcare team is vital. Blood tests and urine samples can help to monitor kidney function and levels of protein in the urine. The outcomes for patients with fibrillary glomerulonephritis are variable- around 50% will develop kidney failure within a few years time. These patients will then need dialysis treatment, or a kidney transplant- however, the progression of fibrillary glomerulonephritis can be slowed down and controlled with early diagnosis and treatment.⁵

Summary

In fibrillary glomerulonephritis, proteinuria is an important clinical indicator, highlighting that the kidneys are not working as well as they should. Proteinuria is often one of the first signs of kidney disease, and higher levels of protein in the urine are linked to faster progression of the condition. Early detection of proteinuria is vital for earlier diagnosis and better outcomes. 

Currently, outcomes for patients with fibrillary glomerulonephritis are fairly poor- many patients will develop kidney failure, and need dialysis or a transplant within a few years of diagnosis. Further research is needed into fibrillary glomerulonephritis, to better understand the cause of the disease, how it develops, and to help develop new, more effective treatments.