Fibrillary glomerulonephritis (FGN) is a rare disease of the kidney, specifically the glomerulus, which is a group of very tiny blood vessels found in the kidney responsible for filtering waste and excess fluid out of the blood. In FGN patients, a large quantity of abnormal proteins, known as fibril proteins, are produced, and they plug the glomeruli walls. This results in a disruption of filtration of the blood, and can lead to serious health complications.¹

FGN primarily affects middle-aged adults, with the average age being 50 years old.³ The exact cause of this disease is not known. However, it is primarily found in people who also have a history of other conditions, including cancer (such as leukaemia and multiple myeloma), autoimmune diseases, diabetes and hepatitis C.¹

This article will focus on the significant health complications which can occur in FGN patients, as well as how the disease is diagnosed and treated. 

Complications in the kidney

Nephrotic syndrome

The fibril proteins, which deposit in the glomeruli in FGN patients, trigger the immune system, the body's system which helps fight off any foreign substance which could cause harm. The immune system will detect these unusual proteins as harmful substances and will attempt to eliminate them through inflammation. However, this inflammation instead damages the delicate holes in the thin glomerular walls, in turn allowing larger molecules to filter out of the blood and into the urine. An example is proteins. When a large amount of proteins pass into the urine, this is known as proteinuria.²

Proteinuria is a significant issue as proteins are very important to us. Some of their crucial functions include helping to build healthy muscles and bones, fight off infection, and make other important substances such as hormones and enzymes.³ Hence, when proteins get filtered out of the blood and into urine, this can lead to serious consequences which can affect multiple organ systems.²

A particularly important protein that gets commonly filtered out of the blood in FGN patients is albumin, a condition known as hypoalbuminemia.⁴ Albumin is the protein responsible for keeping fluid in our blood vessels. Fluid is needed to help the important blood components effectively travel around the body to carry out their important functions.⁵ Low levels of albumin result in fluid from the blood unnecessarily leaking out of blood vessels, affecting blood flow, not allowing important blood components to get to where they need to be, and leading to a build-up of fluid in organs instead, damaging their function.⁴

Symptoms of proteinuria and hypoalbuminemia^2,4 include:

• Swelling (also known as edema) in various parts of the body, including the face, legs, lungs, stomach, and the feet
• Frequent urination
• Dark-coloured urine
• Shortness of breath
• Fatigue
• Nausea
• Muscle cramps
• Hypotonia - weak muscles
• Jaundice - the yellowing of the skin and the eyes
• Foamy or bubbly urine

When a FGN patient experiences proteinuria, hypoalbuminemia and edema, this is collectively known as nephrotic syndrome.⁹

Chronic kidney disease (CKD)

If nephrotic syndrome continues and is not treated, the glomerulus continues to get damaged beyond repair. When this occurs, the damaged tissue is then replaced by scar tissue. With this replacement tissue, the kidneys lose their ability to clean the blood properly. This progressive damage is known as chronic kidney disease (CKD).⁷

If CKD is left untreated, the kidneys start to fail. This is known as end-stage renal disease (ESRD). Roughly 40-50% of FGN patients progress to this end-stage disease after 2-6 years of diagnosis.⁶

Nephrotic syndrome and CKD can lead to knock-on complications in other parts of the body. The following sections of this article will detail examples of this. 

Cardiovascular complications

The cardiovascular system (the heart and blood vessels) can also be compromised in some FGN patients. 

If a patient has proteinuria and/or CKD, this can increase their chances of developing heart disease and suffering from a heart attack.⁷ This is due to the following reasons:

• Hypertension - This is when the pressure in blood vessels is too high. Both proteinuria and CKD can lead to hypertension. This high blood pressure forces the heart to work harder to be able to pump blood around the body. This overworking of the heart is what increases the risk of a heart attack and failure⁷
• Hyperlipidemia - This is the over-production of fats (also known as lipids) in the body. In FGN patients, this can occur due to hypoalbuminemia. An increase in these fats within the blood can result in them being deposited into blood vessel walls, hardening into plaques. This is known as atherosclerosis. Atherosclerosis is a known risk factor for developing heart disease and heart attack. Less blood supply will hence get to the heart, and this will damage the organ⁹

Haematological complications

FGN can also lead to haematological complications, which is when the blood itself is affected. Possible haematological consequences include the following:

• Anaemia - This is the condition where a patient does not have enough healthy red blood cells in their body. FGN patients with CKD can suffer from anaemia, as their damaged kidney can no longer do its important function of producing a substance called erythropoietin. Erythropoietin is the hormone in charge of stimulating the production of healthy red blood cells. In FGN patients, as no such hormone is made, fewer red blood cells are made. As red blood cells are responsible for carrying oxygen around the body, without erythropoietin being made, organs do not get the right amount of oxygen they need to function properly. This can lead to symptoms of fatigue, general weakness, difficulties in breathing, heart problems, irritability and a pale colour of the skin¹⁰
• Thrombosis - This is the condition where clumps of blood (known as clots) form randomly within blood vessels. Nephrotic syndrome in FGN patients can lead to thrombosis. This is because one of the proteins that gets filtered out of the blood in the diseased glomerulus is antithrombin III, which stops blood from clumping together.¹¹ In addition to this, as fluid leaks out of blood vessels and into surrounding organs in FGN patients, due to hypoalbuminemia, the blood that remains within blood vessels becomes thicker, resulting in clot formation. Moreover, proteinuria and CKD stimulate an increase in the production of a substance called fibrinogen, which is a component of blood clots. Thrombosis is dangerous as it can block blood flow, and lead to serious problems including shortness of breath, heart attacks and strokes¹²

Metabolic complications 

FGN can also lead to an imbalance of metabolites within our body. This includes:

• Hyperkalemia - This condition refers to high potassium levels in the blood. This is because the damaged kidney cannot properly filter excess potassium into the urine, and hence a high level remains in the blood. This can lead to serious consequences, such as the damaging of the heart (and this is commonly felt through heart palpitations)¹³
• Hypocalcemia - This condition refers to low levels of calcium in the blood. In FGN patients with CKD, the damaged kidneys cannot perform their function of producing vitamin D, a vital substance needed to allow us to absorb calcium from our food into our blood. Hence, without this production, not enough calcium is present in the blood of FGN patients. This can lead to serious consequences, such as secondary hyperparathyroidism, bone deformities, fractures (breaks in bones), muscle aches, seizures and arrhythmia¹⁴
• Metabolic acidosis - This condition refers to increased levels of acid in the blood. Acid naturally builds up in the blood when people ingest food that contains or results in the production of acid. To neutralise it, the kidneys play an important role by producing a substance called ammonia. However, in FGN patients with CKD, their damaged kidneys cannot make ammonia, resulting in the acid not being neutralised and staying in the blood. This can lead to the serious consequences of osteoporosis, fractures, muscle loss, and in very severe cases even death¹⁵

Uremia complications

Uremia is an FGN complication that occurs in the later stages of the disease, and it refers to waste products not being filtered out of the blood and continuing to circulate the body. Uremia can lead to a whole set of consequences: 

• Uremic pericarditis - Uremia can lead to the irritation and the swelling of the pericardium, which is the thin tissue surrounding the heart. In ESRD patients, the waste products in the blood can travel to this tissue and cause infection, which results in its swelling. Pericarditis can then lead to fluid build-up around the heart, as well as scarring of the heart, all of which impairs the function of the organ and increases the risk of heart disease and attack¹⁶
• Uremic encephalopathy - Uremia can cause dysfunction of the brain. This leads to symptoms of confusion, memory difficulties, changes in personality and in severe cases, coma¹⁷
• Peripheral neuropathy - This is when the nerves found outside of the brain and spinal cord get damaged. Uremia can cause this in late-stage FGN patients. Symptoms include restless legs, cramps and numbness in muscles, weakness of muscles, and the painful burning in legs and arms¹⁸
• Uremic gastroenteropathy - Uremia can also result in the disease of the stomach and the intestines, resulting in patients being constipated or having diarrhoea, vomiting, and not having an appetite¹⁹
• Uremic pruritus - This is the itching of the skin commonly found in FGN patients with CKD²⁰

How is FGN diagnosed?

In order to detect early signs of kidney damage and try to stop FGN from becoming irreversible, analysis of urine and blood tests will help detect protein and/or blood in urine. This is an indicator that the kidneys are not working properly, as large molecules are being filtered out of the blood.¹

To officially diagnose FGN, however, an examination of kidney tissue using electron microscopy needs to be done. This will allow doctors to visualise what is happening in the kidney, and to find evidence of unusual fibril proteins building up in the glomeruli.¹

How is FGN treated? 

No cure has been found for FGN yet, and specific treatment options are quite limited. Doctors focus on using treatments to target specific symptoms and complications individual FGN patients experience, such as proteinuria and hypertension. Moreover, if a patient has another health condition which resulted in the development of FGN, doctors focus on treating the underlying disease, as this often helps improve FGN symptoms. 

Patients who have ESRD and uremia likely require a kidney transplant and/or dialysis, to replace their irreversibly-damaged kidney with a healthy one.¹

Summary

FGN is an uncommon condition of the glomerulus, the part of the kidney responsible for removing waste products and excess fluid out of the blood and into the urine, and keeping proteins and blood cells in the blood. In FGN patients, unusual proteins called fibril proteins block the glomeruli walls, resulting in the activation of the immune system, which in turn damages the glomerulus tissue due to unnecessary inflammation. This damage of the glomerulus affects proper filtration of the blood, and this in turn can lead to a variety of severe health complications. These include protein in the urine (known as proteinuria), swelling due to fluid build-up in organs all over the body (edema), chronic kidney disease, an increased risk of developing heart disease and suffering from a heart attack, anaemia, thrombosis, alterations in metabolite levels in the blood, and waste products remaining within the blood causing infections in different organs. To prevent such serious complications from occurring, it is important to be diagnosed and treated early. Diagnosis occurs through early detection of protein and blood in a patient’s urine, alongside electron microscopy of the kidney. Treatment is currently focused on improving symptoms a patient may experience, and for late-stage cases, kidney transplants and dialysis can be done.