What Is Nephrogenic Systemic Fibrosis?

Introduction

In this article we will talk about a disease called nephrogenic systemic fibrosis (NSF), exploring its patterns and symptoms and explaining in detail the different factors involved in its diagnosis, treatment, and prevention.

So what is nephrogenic systemic fibrosis (NSF)?

Nephrogenic systemic fibrosis is a serious but infrequent condition caused by exposure to certain contrast agents during magnetic resonance imaging (MRI).

NSF can affect anyone, with no distinction of sex or age and can afflict both adults and children. The chances of contracting this condition depend on the amount of renal function and type of contrast agent used.¹    

Briefly, this condition can lead to thickening of the skin and tissues and is the cause of several issues in body organs.

What causes nephrogenic systemic fibrosis?

The precise cause is not fully understood, however nephrogenic systemic fibrosis is thought to be triggered by exposure to gadolinium-based contrast agents, a clear colourless fluid with magnetic properties, this agent is used during MRI to help blood vessels and organs to be seen clearly and help with diagnosis.

Kidney disease is also thought to increase the risk of contracting this condition, as kidneys show a decreased ability to remove this agent from the bloodstream.

In fact, the Food and Drug Administration (FDA) recommends avoiding contrast agents containing gadolinium in people with chronic and acute kidney injury.²

What are other important risk factors?

The risk of developing nephrogenic systemic fibrosis can also be related to other conditions in combination with kidney disease and exposure to a gadolinium contrast agent. These conditions include:

• The use of erythropoietin, a naturally-produced hormone that stimulates blood cell production
• Recent surgery
• Blood clotting problems
• Severe infection
• Other kidney-related conditions, such as kidney surgery, kidney transplant, cancer of the kidney or single kidney
• Dialysis, or the removal of waste products in the blood in the absence of kidneys
• Diabetes mellitus, a condition in which the blood sugar is too high
• Hypertension (high blood pressure)

These risk factors can compromise renal function, leading to an increased chance of contracting this side effect. Patients over the age of 60 can also have an increased susceptibility. If any patient presents any of these risk factors a clinical assessment should be carried out before any kind of gadolinium-based contrast agent is used.¹

What are the main symptoms?

Nephrogenic systemic fibrosis can appear as soon as a few days from exposure to this substance or even years after. The physical symptoms can be painful and lead to severe limitations in movement of the joints, as well as cause internal organ damage.

These symptoms can include:

• Burning and itching skin
• Reddened and darkened areas on the skin
• Skin fibrosis or thickening and scarring of the skin
• Oedema, fluid under tissues causing swelling
• Severe limitations in movement due to loss of flexibility in joints (arms, ankles, wrists, feet, and hands)
• Discolouration of sclera or yellowing of the white layer of the eye
• Fibrosis of internal organs such as lungs and diaphragm (leading to respiratory failure), myocardium, pericardium (heart tissue and membrane), and pleura (the membrane surrounding and protecting the lungs).³

By impacting the organs, this condition can also lead to disability and, in the worst cases, to death. ⁴

How is nephrogenic systemic fibrosis diagnosed?

This condition is not diagnosed through specific testing, but a good medical history, involving the use of MRI and the presence of advanced kidney disease, physical examination and exclusion of other conditions, can lead to the right diagnosis.

A biopsy (sample) of the affected organ or tissues can also help support the diagnosis.^1,2

How can we treat nephrogenic systemic fibrosis?

To this day there is still no cure for this condition, and no treatment is effective at stopping or reversing its progression.

Nephrogenic systemic fibrosis is considered a rare disease, which means studies for this disease are harder to conduct, making it difficult to make significant discoveries.

Different treatments have been known to show results; however, further research is needed to understand whether these treatments can really help. These treatments include:

• Haemodialysis: after the administration of a gadolinium-based contrast agent, haemodialysis⁸ can help people with advanced-stage chronic kidney disease, and any kidney-related disease, by reducing the risk of this side effect.
• Physical therapy: stretching of the limbs has the potential to slow down the progression of the loss in flexibility of the joints and help maintain freedom of movement.
• Kidney transplant: in particular cases, a kidney transplant may help improve renal function, reducing the symptoms of the disease over time.
• Extracorporeal photopheresis (ECP) with ultraviolet light A is a therapy that works by removing blood from the patient’s body. The blood is then treated with a light-sensitising drug and exposed to UV light, before being introduced back into the patient's body. This treatment has shown positive outcomes for some patients.²

Medications for this condition are considered mostly experimental and are not used. While some patients have shown positive effects, the side effects can make it challenging to use them.These medications include:

• Imatinib (Gleevec): helps with the reduction of skin thickening but needs more research.
• Pentoxifylline (Pentoxil): this treatment offers  limited success in helping circulation, however more research is required.
• Sodium thiosulfate: this treatment has also shown improvements but requires more research.
• High-dose immune globulin: this medication has shown possible benefits but requires further research.²

How can nephrogenic systemic fibrosis be prevented?

Prevention measures have been put into place in previous years and the incidence of nephrogenic systemic fibrosis has been reduced greatly:¹ 

• Guidelines have been put into place by authorities such as the FDA, American College of Radiology (ACR) and the European Society of Urogenital Radiology (ESUR) advising radiologists against the use of gadolinium-based contrast agents on patients with renal conditions.
• Examination of patients at risk before the use of these agents
• Early haemodialysis for patients affected by NSF after MRI with the use of gadolinium

Conclusion

• Nephrogenic systemic fibrosis is a rare but serious condition affecting people with kidney disease.
• It is a side effect caused by the use of type 1 gadolinium-based contrast agents used during MRI scans.
• It can be contracted by anyone without distinction of sex and age, but people over the age of 60 have a higher risk.
• It causes the skin to thicken, joint pain and organ damage. It can also result in reduced mobility and lead to death.
• There is no cure, but various treatments can help manage and slow down the disease.
• Patients with kidney disease should be evaluated before undergoing MRI.

FAQs

What are the symptoms of nephrogenic fibrosis?

The symptoms of nephrogenic systemic fibrosis can involve skin conditions such as red and dark areas on the skin, itchiness and burning sensations, thickening and scarring of skin and internal organs, and can also lead to limitation of movement. In worst cases, this condition can lead to death.

Is nephrogenic systemic fibrosis curable?

There is currently no cure for nephrogenic systemic fibrosis; experimental treatments are available, however research is still ongoing.

How long does it take for nephrogenic systemic fibrosis to occur?

Nephrogenic systemic fibrosis can manifest anytime after exposure, this could mean days or even years.

What is the meaning of the word nephrogenic?

Nephrogenic signifies a process originating in the kidney.