What Is Fibrillary Glomerulonephritis?

You may have come to this page after being told you have a condition called fibrillary glomerulonephritis (FGN) and wanted to know more. Apart from being difficult to pronounce, many people will not have heard of it before. After reading this article, you will have learnt useful information, including:

• Symptoms you may experience.
• Available treatments.
• The long-term outlook 

Overview of fibrillary glomerulonephritis

FGN is a disease affecting the kidneys. Your kidneys filter the blood through millions of filtering units called glomeruli, removing waste and producing urine. In this disease, these filters get clogged up with proteins that have been made by your body. This means the kidneys may not function properly, producing symptoms and potentially progressing to kidney failure.¹

What causes it?

Recently, a protein called DNAJB9 was found in abundance in those with FGN compared to patients with other diseases affecting the kidneys and healthy subjects. What role this protein plays is debatable, although there is the suggestion that it may cause the body’s immune system to attack normal cells.² At the present moment, however, this remains only a theory, and there are no definitive answers.

What are the signs and symptoms?

Because the filtering units are damaged, proteins that are meant to stay in your blood pass through them and into your urine. This is called proteinuria and is seen in virtually every case. There is also a high likelihood of having blood in your urine (haematuria).  When presenting to your healthcare professional, you may have decreased kidney function (renal insufficiency) and high blood pressure (hypertension).²

Because of the proteinuria, you will have less protein in your blood, and this can cause swelling in your legs or feet.

As kidney function deteriorates, other issues may develop, such as anaemia – a lack of healthy red blood cells or the haemoglobin that’s in them, which transports oxygen around the body.  Once kidney failure occurs, there can be fatigue, nausea, confusion, shortness of breath and general weakness.

Who gets fibrillary glomerulonephritis, and what are the risk factors?

Most adults are diagnosed in middle age, with the average age taken from 3 studies being 57, although it has been found in children to those in their eighties.³ It tends to affect white people more than others, and those assigned female at birth (AFAB) are represented slightly more.⁴

There may be an association with malignancy, diabetes and autoimmune disorders (where the immune system attacks the body), as these conditions were seen in people with FGN in studies.  Examples of some of the autoimmune diseases observed included Crohn’s disease, lupus and a condition affecting the thyroid called Grave’s disease.

Hepatitis C virus infection was also present in certain people in some studies, meaning it may be worthwhile to be tested.²

Many cases, however, have no underlying disease.

How is it diagnosed?

Routine tests may show that there’s a problem with the kidneys.  This might be the presence of protein or microscopic amounts of blood in the urine.  Further tests would then be carried out, but diagnosis can be a challenge and take some time as the only definitive way to identify FGN is by using a powerful microscope called an electron microscope on samples taken from a kidney biopsy. This will look for the proteins, called “fibrils”, that are building up in the filtering units.  Even then, early-stage cases may not show these fibrils, and other conditions can appear similar in the various tests, making diagnosis even trickier.⁵

One study in 2022 evaluated whether the protein mentioned earlier, DNAJB9, could be reliably used to diagnose FGN. It found that it was a good marker of FGN, even in early-stage cases and cases that weren’t the standard type.⁵

Tests to look out for other associated conditions will often be ordered as well.

What are the treatment options?

As it is such a rare disease, there are no large randomised controlled trials available to help healthcare professionals choose a therapy that targets the disease specifically. That said, controlling blood pressure is recommended and can be helped with drugs called angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs). Having a low-sodium diet may be advised, as this reduces swelling and can decrease blood pressure. You could also be given drugs that lower the amount of fats (including cholesterol) in your blood if they are found to be high.¹

Studies investigating drugs that suppress the immune system have been relatively small and didn’t seem to show a benefit. Although some patients responded to the drugs, and one called rituximab may help with proteinuria, there isn’t enough data to draw conclusions on giving immunosuppressive therapy for FGN.^1,6

In patients where there is an associated condition, treatment of the underlying disorder may provide benefit.

Patients who have a chronic Hepatitis C virus infection should be treated appropriately for that infection, but the evidence that this improves FGN is lacking.¹

Healthcare professionals will want to monitor you for signs of kidney disease progression after you’ve been diagnosed, and if it gets to a certain stage, you may be offered an immunosuppressive treatment like rituximab or other options such as steroids, cyclophosphamide, mycophenolate mofetil (MMF), and cyclosporine.⁷

What is the long-term outlook?

While there are limited treatment options available, some cases get better spontaneously with good blood pressure control.  Complete or partial remission is possible and is more likely in those with milder disease.  However, roughly 40-50% of those with FGN progress to kidney failure, also known as end-stage renal disease (ESRD) within 2-6 years.¹

In one study, 61 people with FGN had their kidney biopsies assessed under a microscope and were followed up after diagnosis. The average time it took those who developed kidney failure varied by the type of histology (what it looked like under the microscope), with one type called “diffuse sclerosing” averaging only 7 months, while the longest was “membranous glomerulonephritis” at 87 months.  The amount of creatinine, which is used to measure kidney function, at diagnosis was a good predictor of who would progress to kidney failure. 18% who had a lower creatinine developed kidney failure, while 72% did from the higher group.⁸

What happens if I reach end-stage renal disease?

In this scenario, a treatment called dialysis is available. This is when a machine does the work of your kidneys, removing waste and excess fluid from your blood. It is necessary as the waste products and excess fluid can cause damage to your body if their levels are high. Another option is transplantation if you are eligible.

There are two main types of dialysis: haemodialysis and peritoneal dialysis.

Haemodialysis

This is when the machine removes blood from your body through a needle in your arm. The blood then passes through a filter, removing waste via a cleaning fluid.

Peritoneal dialysis

A thin tube called a catheter is passed into your abdomen (tummy) and uses a lining in your body (the peritoneum) as a filter.

The abdomen is filled with cleaning fluid, and after some time, it is removed, taking away the excess fluid and waste.

Transplantation

A transplant represents the best option as a treatment and is when a healthy kidney from a donor is placed inside your body to do the functions of your own kidneys. If successful, it may give you a longer lifespan and a less restricted life.^9,10

Unfortunately, the disease can reoccur in the transplanted kidney. One study that looked at 14 patients after their transplant found 3 developed FGN again after an average of 5 years and beyond.¹⁰

What lifestyle changes can I make?

You can adopt a kidney-healthy diet by making the following changes:

• Choosing low-salt foods so your sodium intake is lower.
• Ensuring your diet is rich in fruits, vegetables, legumes, fish, poultry, and whole grains.
• Consuming low-fat and cholesterol products and eating more fibre helps lower cholesterol in the blood.
• Sometimes, you may be advised to restrict your fluid and protein intake – check with your healthcare professional before making this change.

Keeping physically fit and looking after your mental health is another important part of therapy.  Having open conversations with others and seeking help when needed – whether through counselling or some other option could help you cope with living with this disease.

https://unckidneycenter.org/2015/04/fibrillary-glomerulonephritis/

Summary

You will have hopefully gained some valuable insights into this rare condition that affects the filtering units of the kidneys.  The course of the disease varies between individuals, and while the possibility of remission exists, a significant amount faces progression to kidney failure.

FGN affects white people, and people AFAB slightly more, and the cause of it is still being investigated.  Diagnosis is reliant on a kidney biopsy, and most people first present with protein and microscopic amounts of blood in their urine.

Although treatment remains elusive, good blood pressure control, fat-lowering drugs, dietary changes, and potentially immunosuppressive therapies are the main ways in which it can be managed.

If you do reach ESRD, then dialysis can replace the function of your kidneys for a period, and then there is always the possibility of a transplant providing a healthy kidney without the disease recurring.

With time, there may be further, larger trials to guide optimum treatment, while in the present, it would be worthwhile trying to find support for living with a rare kidney disease.