Fibrillary Glomerulonephritis (FGN) is a rare and progressive disease that affects the kidneys' function. Let’s delve deeper to better understand FGN, including what typical symptoms look like, the potential treatment options and what causes it.

Introduction

What is fibrillary glomerulonephritis?

To remove waste and extra water from the blood during the urine production, healthy kidneys usually filter about a cup of blood every minute. There are millions of these filtering units in the kidney, named nephrons. Each nephron has a blood filter called the glomerulus, and a tubule which removes excess waste and allows essential minerals to be reabsorbed back into the blood.¹

FGN is a disease that affects the kidneys’ glomeruli. The body of individuals with FGN produces large quantities of abnormal proteins, called fibres, which enter the glomeruli, disrupting the filtration as the proteins get stuck. This results in the over-activation of the immune system, which leads to swelling within the kidneys. Over time, the constant inflammation damages the glomeruli, and the fibres spill into the urine, leading to increased damage to the kidney and the formation of scar tissue. Ultimately, the kidneys lose the ability to function and filter waste from the blood.² The word “fibrillary” in FGN refers to the protein fibres, and “glomerulonephritis” refers to the swelling in the kidneys’ glomeruli.³

Who gets fibrillary glomerulonephritis?

FGN is rare and is present in 0.5% to 1.4% of native kidney biopsies.⁴ The disease can be found in patients aged from as young as 10 to 89, and seems to affect Caucasians more than other races.³ It has been linked to people with autoimmune diseases, HIV, hepatitis C viral infections and some cancers. Therefore, these individuals must be screened for FGN.⁴

What are the symptoms of fibrillary glomerulonephritis?

FGN is a progressive disease; symptoms usually start gradually and worsen over time, however, symptoms can arise abruptly and all at once. The disease can lead to kidney failure as they stop working entirely, resulting in the need for dialysis and kidney transplants.² Some of the most common FGN-associated symptoms are as follows:

Blood in the urine (hematuria)

Red blood cells are not normally found in urine; however, due to kidney damage and inflammation in patients with FGN, blood may leak into the urine. This symptom of FGN is clinically called hematuria. It occurs when the filters in the kidney are damaged, and since FGN involves glomerular damage, hematuria is a common characteristic in patients. There are two types of hematuria: microscopic hematuria, which means that blood cannot be seen with the naked eye and a microscope is needed to view the red blood cells, and gross hematuria, which is the detection of blood in the urine with the naked eye, as urine tends to be tea or cola-coloured.⁵

Protein in the urine (proteinuria)

Another common symptom of FGN is an abnormal amount of protein in the urine, or proteinuria. Most proteins are too large for kidney filters, so they are not normally found in the urine, but when kidney filters are damaged and do not function properly, as in individuals with FGN, protein gets lost in the urine. The sign of proteinuria is the presence of frothy urine.⁶

High blood pressure (hypertension)

Patients develop hypertension, or high blood pressure, because the kidneys have a role in regulating blood pressure. When kidneys become dysfunctional, the excess waste and fluids that cannot be removed raise blood pressure in the body. High blood pressure then contributes to damage in the kidney blood vessels, thus creating a cycle of deteriorating kidney function.⁷

Other symptoms

Patients with FGN may have swelling in their legs and feet and anaemia. Kidney failure is a risk to patients, with signs of kidney failure being nausea, itching, fatigue, shortness of breath, confusion or heart palpitations.² Patients also lose the ability to excrete phosphorus by the kidneys, which is an important mineral for several important functions. Long-term elevated phosphorus in the body increases the risk of end-stage renal disease and cardiovascular disease.⁸

How do we detect fibrillary glomerulonephritis?

Blood tests performed may indicate whether there is waste build-up in the blood due to kidney dysfunction. Urinalysis may be performed when the patient notices foamy urine or the presence of blood in their urine, as blood could indicate kidney damage, and foamy urine may indicate protein presence. However, this is not unique to FGN as other conditions also involve damage to the kidney’s glomeruli filter ², such as Immunotactoid glomerulopathy, fibronectin glomerulopathy and collagenofibrotic glomerulopathy.³ These diseases differ in the type of protein that disrupts and damages the kidney filter function.

To detect FGN, tests must be performed to determine which proteins are affecting the glomeruli. This involves the performance of a kidney biopsy, a procedure that removes tiny pieces of the kidney tissue.⁹ Clinicians then examine the tissue under a microscope, specifically an electron microscope, which allows them to determine the type of proteins building up in the kidneys. Only then can clinicians provide a firm diagnosis.² 

What are the treatment options for fibrillary glomerulonephritis?

There is currently no FGN treatment, with many therapies previously tried but deemed ineffective. Therefore, clinicians tend to focus on managing FGN and reducing its symptoms, such as proteinuria and high blood pressure.³ To reduce hypertension, patients are prescribed renin-angiotensin system blockade, which is a drug that is known to not only control blood pressure but also decrease proteinuria. Taking this drug means that the progression to entire kidney failure is slowed down.¹⁰

Steroids may be prescribed, which help reduce swelling by suppressing the overactivation of the immune system. Similarly, immunosuppressants, like steroids, may be prescribed, which suppress the immune system. However, these increase the risk of infections since immunity is impaired.

Plasma exchange is a procedure performed to remove some plasma from the blood. Plasma is a fluid in the blood that has substances that cause inflammation in the kidneys. To reduce swelling in the kidneys, plasma is removed from the blood cells, replaced with a substitute, and then placed back into the body. This may be performed when disease progression becomes severe.

Clinicians may advise patients with FGN to make dietary changes, such as decreasing fat, salt, potassium and protein intake. These help control and reduce blood pressure and keep body fluids at a normal level.

If kidney failure occurs, kidney dialysis is a treatment offered to patients that involves filtering the blood of waste manually. However, most commonly for patients with kidney failure, a kidney transplant will be required.¹¹

What is the prognosis of fibrillary glomerulonephritis?

Unfortunately, the prognosis in FGN is poor, the cause of the disease is unknown, and almost half of FGN patients experience kidney failure. This highlights the importance of understanding FGN, as it begins and develops, to prevent/ treat it better.

Future research is underway on novel treatment methods to manage FGN. For example, several studies have been conducted on an immunosuppressant drug named rituximab, which has already shown some promise for the future. Some studies have shown that rituximab given to patients stabilised kidney functions, while some studies show that it is effective when given at the early stages of FGN before chronic kidney damage has occurred. Additionally, recent studies have found a way to detect FGN more easily, improving the rate of diagnosis. This is done by discovering a biomarker of FGN specific to the disease.¹⁰

Summary

Fibrillary Glomerulonephritis (FGN) is a rare kidney disease caused by a build-up of small protein fibres in the kidneys’ glomeruli that, over time, lead to the kidneys not working properly. Typical symptoms of FGN include high blood pressure (hypertension), protein in the urine (proteinuria), blood in the urine (hematuria), swelling, and kidney function problems. Seeking medical attention when these symptoms arise at an early stage is important, as early treatment can help with the management of the disease and prevent kidney failure. 

FGN is diagnosed through urine tests, kidney biopsies and tissue studies under microscopes, which ensures that the specific protein that affects FGN is detected to establish an accurate diagnosis. Unfortunately, there is no FGN cure; however, there are numerous management treatment strategies to decrease/manage symptoms. Moreover, much research is underway to find a more suitable treatment to improve quality of life.