Overview

Fibrillary glomerulonephritis (FGN) is a rare condition that causes inflammation in the glomeruli, the part of the kidney responsible for filtering water and waste products out of the blood. It is caused by the deposit of fibril proteins and is often secondary to other health conditions, such as diabetes, cancer, and autoimmune conditions. Symptoms of this condition are often detected on routine urine tests. Whilst different medications can be prescribed at the early stages of this condition, it can quickly progress to end-stage renal failure, requiring dialysis and eventually a kidney transplant. 

Structure and function of the glomerulus

The glomerulus is the part of the kidney that filters excess liquid and waste products out of your blood.  It is made up of a collection of capillaries (small blood vessels) enclosed within a sac called the Bowman’s capsule. It is located at the proximal region of the nephrons (functional units of the kidneys). The blood flows into the capillary network through an afferent arteriole, gets filtered, and then leaves the glomerulus to continue around the body via the efferent arteriole. The filtrate collected then drains into the collecting ducts via a tubule and will become urine. The two arterioles moderate the flow of blood through the glomerulus as necessary by constricting and dilating, maintaining high pressure in the glomerulus to ensure a fast filtration rate.² 

The capillaries of the glomerulus have many unique characteristics that allow them to perform their specific job. The endothelial cells of the capillaries contain many fenestrations (small pores) that allow for quick filtering of the blood. The arterioles are made up of smooth muscle cells which can constrict and dilate, allowing them to control the flow of blood into the glomerulus. Finally, special endothelial cells called podocytes surround the capillaries, which prevent plasma proteins from entering the filtrate.³  

How does the glomerulus filter the blood?

As blood flows into the glomerulus, the thin capillary walls allow smaller molecules, waste products, electrolytes, and water to pass into the neighboring tubule. The larger molecules, such as proteins and blood cells, remain in the bloodstream. As the filtered fluid runs along the tubule, much of the molecules in the filtrate are reabsorbed. Any remaining fluid and wastes then leave the body as urine.  

Pathophysiology and presentations of fibrillary glomerulonephritis

Fibrillary glomerulonephritis is a condition involving inflammation and damage to the glomeruli. It is often caused by your immune system attacking the tissues in the kidney.⁴ Some cases of glomerulonephritis are mild and may only be picked up incidentally by blood tests. More severe cases can cause symptoms such as dark and frothy urine due to the presence of blood and proteins. 

In fibrillary glomerulonephritis (FGN), this inflammation is caused by deposits of unusual fibril proteins in the kidney. These fibril proteins are immunoglobulins produced by the body’s immune system.⁵ They can get trapped in the capillary layers, blocking the filtration and causing inflammation in the tissues. Over time, this can then cause permanent damage to the structures, which affects the kidney’s ability to function effectively and eventually leads to renal failure. 

Causes

Fibrillary glomerulonephritis (FGN) is a relatively rare condition, being present in 0.5-1% of kidney biopsies.⁶ Whilst the cause of fibrillary glomerulonephritis is unknown, it tends to affect middle-aged adults between the ages of 40 and 80 and mostly occurs in people with other health conditions, such as diabetes, high blood pressure, cancer, and autoimmune conditions.¹ 

Symptoms

The symptoms of fibrillary glomerulonephritis are similar to the symptoms of any other type of glomerulonephritis. 

• Proteinuria: high levels of protein in the urine. It is usually picked up in a urine test, but can sometimes be seen as “frothy” urine
• Hematuria: the presence of blood in the urine. Microscopic blood is picked up in urine tests; larger amounts can be seen as very dark urine
• Swelling in the legs and feet

As the condition develops and kidney function starts to deteriorate, other symptoms can develop, including:

• High blood pressure 
• Anaemia

Tests for fibrillary glomerulonephritis

Early symptoms of FGN may be picked up by routine lab tests, such as blood or protein in the urine. However, many other conditions can cause these symptoms. A diagnosis of FGN specifically can only be made by microscopic examination of kidney tissue, which will show protein build-up in the glomeruli.⁵  Electron microscopy is then needed to determine the kind of proteins that are present. Under the microscope, FGN presents as straight fibrils that are arranged randomly in two areas of the glomeruli: the mesangium and the glomerular basement membrane.⁷ The fibrils are larger than those of amyloidosis (another condition that produces fibril proteins) at between 10 nm to 30 nm. Immunofluorescence can also be used to confirm FGN.

Treatment for fibrillary glomerulonephritis

There are currently no specific guidelines for the treatment of fibrillary glomerulonephritis.⁷ If FGN is caused by another condition, this must first be identified and treated. Otherwise, treatment will be based on the severity of the condition. Medications such as anti-proteinuric agents, like angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, may be prescribed.⁷  As the disease progresses, steroids, chemotherapy drugs, and immunotherapy may also be used. Eventually, as the function of the kidney declines, dialysis and a kidney transplant may be required. 

Prognosis for fibrillary glomerulonephritis

The prognosis for FGN is poor, with close to one-half of patients progressing to end-stage renal disease within a few years after diagnosis.⁸

FAQs

What is fibrillary glomerulonephritis in lupus?

Fibrillary glomerulonephritis is the inflammation of the glomeruli due to fibril protein deposits. This occurs mostly in people with other health conditions, such as diabetes, hypertension, cancer, and autoimmune conditions, such as lupus.¹

What happens to the glomeruli structure in fibrillary glomerulonephritis?

In fibrillary glomerulonephritis, deposits of unusual fibril proteins become trapped in the capillary layers of the glomeruli. This can block filtration, leading to inflammation in the tissues. Over time, this can then cause permanent damage to the structures, which affects the kidney’s ability to function effectively and eventually leads to renal failure.