Overview

With less than 1% of kidney disease cases being due to fibrillary glomerulonephritis (FGN), this condition affecting the filtration properties of the kidneys is extremely rare.¹ The kidneys are important organs, filtering out waste from the blood and maintaining healthy levels of water, salt and minerals in our blood. Problems with the kidneys can have knock-on effects throughout the body, hence it is vital to keep an eye out for any signs or symptoms that could indicate these problems. This article highlights the role of the kidneys and how fibrillary glomerulonephritis can affect their function. 

The kidneys

Where are the kidneys located?

Just below the rib cage, on either side of the spine, are two fist-sized organs known as the kidneys. These bean-shaped organs are part of a wider system known as the urinary tract. This system is made up of the ureters, the bladder and the urethra, in addition to the kidneys (Figure 1).²

What do the kidneys do?

The kidneys primarily function by filtering blood that is circulated in the body, to ultimately produce waste products that make up urine. They also ensure that there is a healthy balance of water, salt and essential minerals in the blood. Our bodies rely on the right mix of calcium, potassium and sodium; if this balance is skewed, it will noticeably affect the function of other organs.²

The two main regions of the kidney are the medulla (inner part) and cortex (outer part). The small unit responsible for blood filtration is known as the nephron (a tube that loops between the cortex and medulla). There are around 1 million nephrons in each kidney, which work together to efficiently filter out all the surplus or unwanted molecules in the blood (Figure 2).³

Each nephron is supplied with blood through a small bundle of blood vessels called the glomerulus.⁴ Water and most other small molecules can filter through the thin walls of the blood vessel into the nephron's tubes. Here, essential minerals and water are reabsorbed into the bloodstream, leaving only the excess molecules and waste products that make up urine.

What is fibrillary glomerulonephritis? 

Fibrillary glomerulonephritis is a rare disease that affects the glomerulus in the kidneys. It is characterised by the abnormal buildup of long proteins in the glomeruli, which become tangled and clogged. This disrupts the effective blood filtration abilities of the kidneys.¹

Causes

The cause of fibrillary glomerulonephritis is currently unknown. Despite its rare nature, the condition has gained research attention with many researchers looking at similar conditions to try and gain an insight into potential triggers and causes.¹

Signs and symptoms

People with fibrillary glomerulonephritis present with symptoms and signs akin to those of other kidney diseases (Figure 3), including:⁵

• High blood pressure (hypertension)
• Blood in the urine
• Protein in the urine often gives rise to a foamy appearance
• Poor kidney function results in changes to the amount of urine produced
• Nausea
• Fatigue

How it differs from other glomerular diseases 

Fibrillary glomerulonephritis is distinguished from other kidney and glomerular diseases through the identification of a substance called DNAJB9 (a molecule that sticks to abnormally shaped proteins). In healthy individuals, there are usually low levels of DNAJB9 in the kidneys. With the long misfolded proteins present in fibrillary glomerulonephritis, the levels of DNAJB9 increase in the kidneys – as a way of tagging the abnormal proteins – to attract the attention of immune cells. Testing for this specific marker protein in suspected cases of fibrillary glomerulonephritis increases the chances of an accurate diagnosis.¹

How does fibrillary glomerulonephritis impact kidney function?

Clogging the kidneys with abnormal proteins can activate the immune system. As previously mentioned, DNAJB9 attaches to these proteins and signals to immune cells as a call to action. This generally induces swelling of the area and triggers an inflammatory response. Swelling of delicate areas, like the glomerulus of the kidneys, can lead to further damage.⁶

Over time, this damage worsens and reduces the efficiency of blood filtration, allowing much larger proteins to pass through the filters. This is why high protein levels are detected in the urine of individuals with kidney problems.⁷

Blockage of these filters can also cause waste products to build up in the bloodstream, which triggers activation of the immune system throughout the body. If left untreated, this can result in kidney failure and can be fatal.⁶

Treatment

Currently, there are no available treatments for fibrillary glomerulonephritis that have proven to be effective. In an attempt to reduce swelling of the kidneys in this condition, steroids are often used to prevent further damage from the activated immune system. In some cases, a special type of filtration process called plasmapheresis has been used in an attempt to remove protein from the blood outside of the body. However, unless the cause of the condition is treated, external filtration is only beneficial in the short term. If fibrillary glomerulonephritis reaches a point where the kidney can no longer recover, a final option is a kidney transplant.⁷

FAQs

Is fibrillary glomerulonephritis hereditary?

There is little evidence to suggest that fibrillary glomerulonephritis can be passed down through families, however, this has been reported in very rare instances.⁸

What is the prognosis for fibrillary glomerulonephritis?

The prognosis for fibrillary glomerulonephritis is generally quite poor, with between 40-50% of those diagnosed progressing to end-stage kidney disease within a few years.⁹

Is it possible to prevent the onset of fibrillary glomerulonephritis?

While there is little research on preventing the onset of this condition, maintaining a healthy lifestyle and eating a balanced diet will help keep the kidneys healthy. In particular, high blood pressure puts the kidneys under extra stress.¹⁰ By aiming to keep blood pressure at an ideal level, the onset of kidney disease is less likely. 

What is the average age of onset for fibrillary glomerulonephritis?

Fibrillary glomerulonephritis usually starts at the age of 50 years, however, in some cases, the onset can be earlier.¹¹

Summary

Fibrillary glomerulonephritis (FGN) is a rare kidney disease that affects less than 1% of kidney disease cases. The kidneys filter waste from the blood and maintain balanced mineral levels. In FGN, abnormal protein buildup clogs the kidney's filtration units, disrupting their function.

Symptoms often resemble other kidney diseases, including high blood pressure, blood in urine, protein-rich urine, urine output changes, nausea, and fatigue. FGN is unique due to the high levels of DNAJB9 in the kidneys, a marker protein that signals immune cells to attack abnormal proteins. 

The disease stems from unknown causes, though researchers are exploring similar conditions for clues. Over time, these protein buildups reduce kidney efficiency, leading to potential kidney failure, as larger proteins and waste accumulate in the bloodstream. Without effective treatments, doctors use steroids to manage kidney swelling and sometimes perform plasmapheresis to filter proteins externally.

However, plasmapheresis is only a temporary solution. A kidney transplant becomes necessary if the kidney sustains irreversible damage. Despite its rarity, FGN requires early diagnosis to mitigate its serious consequences on kidney function and overall health.