Overview

Fibrillary Glomerulonephritis (FGM) is a rare disease in which the filtering structure of the kidney, known as the glomeruli, is damaged due to inflammation. It is caused by the deposition of proteins in the capillaries which deteriorates filtering capabilities, resulting in toxic buildup, loss of blood cells, high blood pressure (hypertension) and other renal dysfunction. The disease is typically observed in middle-aged adults, with varying female-to-male ratios reported between studies.¹ There is a general agreement that outcomes for FGM are poor, with many requiring kidney transplants due to persistent renal dysfunction or complete kidney failure. The lack of standardised treatment complicates prognosis and disease management, with most treatments relying on the management of symptoms rather than the treatment of the disease itself. Although the precise pathophysiology of FGM was vaguely understood until recently, studies have highlighted its strong association with infections and autoimmune diseases, which has helped to introduce a more structured and personalised approach to treating the disease.

Overview of disease

Symptoms

The primary function of the kidney is homeostasis, in other words, the control of internal properties in the body to achieve a steady state. FGM disrupts this because the body is not able to filter out unwanted chemicals. Therefore, the symptoms of FGM would typically appear in the uria, but more widespread and systemic signs may be found too. Typical symptoms include the following: 

• Excess protein in urine resulting in foamy or bubbled uria (proteinuria)
• Dark-coloured urine due to excess blood cells
• Joint or stomach pain
• Rashes, jaundice, fatigue, loss of appetite
• Reduced urine frequency

Symptoms would differ depending on the cause, and it is unlikely that the patient expresses all symptoms. However, studies do agree that proteinuria is a highly common symptom associated with FGM.²

Causes of FGM

The precise aetiology of FGM has been long unknown, although recent studies have revealed varying associations with infectious disease, autoimmune diseases and cancer.³ The common mechanism that contributes to FGM among those conditions is the production of antibodies by the immune system, which deposits at the glomeruli.

Infectious diseases

One pathogen that is likely to cause FGM is a bacteria called streptococcal bacteria. In recent years, there has been an increase in FGM caused by infections at the heart (endocarditis), throat or skin by streptococcal bacteria.⁴

Other pathogens that may trigger FGM are viral infections by Hepatitis C or Human Immunodeficiency Virus (HIV), although the latter has only been reported in 2 case studies.^5,6

Autoimmune diseases

Autoimmune diseases can also produce large amounts of antibodies, which may cause inflammation at the glomeruli, resulting in FGM. Examples include Lupus, goodpasture’s syndrome and IgA nephropathy.

Other causes

Inflammatory diseases such as vasculitis or other conditions that cause sclerosis, including diabetes and hypertension are known to cause FGM, albeit at much lower frequency than infectious diseases. There is sparse evidence of genetic factors, while cancer is also thought to contribute to FGM, even though there may be a lack of understanding of its mechanism.^7,8

Diagnosis

Diagnosis of FGM has been long limited to kidney biopsy.⁹ This was an issue as it is relatively invasive and requires electron microscopy which may be unavailable in many countries. With that said recent advances have helped to identify a biomarker known as DnaJ homolog subfamily B member 9 (DNAJB9).¹⁰ This has opened up a possible diagnosis method that is more standardised and accessible compared to its predecessors. Further research is required, however, to confirm if DNAJB9 is a targettable molecule for treatment or merely a measurable biomarker. It is also unknown whether DNAJB9 is an autoantigen that contributes to the inflammation of glomeruli, or is simply a protein associated with its pathophysiology.

Prognosis and Outcome of FGN

How severe is FGN?

Date on outcome

A study led by Samih H. Nasr in 2011 reported the following data on how 66 patients with FGN fared 4 years after monitoring:¹¹ 

• 13% with complete/partial remission
• 43% with persistent renal dysfunction
• 44% with progression to end-stage renal disease (ESRD)

The general consensus based on these numbers is that the prognosis of FGN is poor, with a large portion of patients who develop ERSD requiring kidney transplant or dialysis. 

Complications associated with FGN

The deteriorated filtering ability of the kidney results in toxic accumulation, poor homeostasis of nutrients and loss of proteins and red blood cells (RBCs). When such issues are left untreated in the long term, this results in acute kidney failure, chronic kidney disease, hypertension and nephrotic syndrome. Its systemic effect also contributes to a range of conditions that are not directly associated with the kidney, notably cardiovascular diseases. 

The diverse aetiology of FGN also increases the complexity of disease management. FGN induced by microbial infection requires treatment for the infecting pathogen, while those caused by autoimmune diseases may reveal underlying genetic mutations. Some diseases that occur in tandem may be rare, for example, Behcet Syndrome, which would further complicate treatment due to the lack of, or limited options.¹² Studies also reveal that up to 10% of patients with FGN have monoclonal gammopathy (conditions where abnormal antibodies are found in the blood). This can also give rise to complications in identifying the cause of FGN.¹³

Treatment for FGN

As of today, there is a lack of standardised treatment due to the rarity of FGM. Most treatments focus on the management of symptoms, for example using Renin-angiotensin-aldosterone system blockers (anti-hypertensives) and immunosuppressives (to reduce inflammation).¹⁴

Other approaches, such as the use of steroids, plasmapheresis, cyclophosphamide and cyclosporine have been of little success. Clinical studies suggest a possible role of monoclonal antibody treatment too, although further testing is required.¹⁴ A third of Patients who undergo kidney replacement may develop the disease again but at a much lower severity.¹⁰

Prevention

Prevention of FGM is usually dependent on preventing/avoiding diseases that can cause FGM, including infections and hypertension. Hygiene and safe sex are crucial for the former, while those who have high blood pressure may consider a healthier diet with less intake of sodium. Although the evidence may be little, there seem to be some genetic risk factors too, therefore testing could be considered if a family member has FGM. 

FAQ’s

What is the difference between FGM and Nephrotic syndrome?

Symptoms of FGM may be mistaken for nephrotic syndrome – another disease that occurs in the kidney. A key difference between the two diseases is that nephrotic syndrome is associated with greater proteinuria and the uria may appear more bubbly/fuzzy.

Is FGM and chronic kidney disease (CKD) the same thing?

No, FGM and CKD are two different conditions. FGM is one of the causes that result in CKD, alongside interstitial nephritis and polycystic kidney disease.

Is FGM considered as a disability?

Yes. Alongside many kidney diseases, FGM is considered to be a disability and patients can apply for a range of social support schemes.

How can I manage proteinuria at home?

There are many ways in which you can reduce protein in uria before visiting a clinic. One example is to reduce sodium in the diet to manage hypertension. You can also reduce your protein intake. In turn, increasing fibre-rich food in the diet can help to manage blood sugar levels and cholesterol, which are both beneficial to managing proteinuria. Drinking a lot of water has little positive effects. You may also consider reducing the usage of non-steroidal anti-inflammatory drugs (NSAIDs), although you should seek advice from a medical professional. 

Summary

FGM is a disease that has rightfully attracted intense research interest in recent years, and further studies would help standardisation of treatment to yield consistent disease prognosis. The introduction of the non-invasive biomarker DNAJB9 would allow easier and quicker diagnosis of the disease, which can allow strategised long-term treatment plans. An increase in case studies and data recording thanks to more scientific interest can greatly accelerate the study of its precise disease mechanism. With that said, its complex aetiology still remains, meaning some level of complication during the treatment of FGM would be unavoidable. The current aim is to increase research findings regarding the pathophysiology of FGM, to allow a more individualised treatment for patients.