Nephrogenic Systemic Fibrosis

What is nephrogenic systemic fibrosis?

Nephrogenic systemic fibrosis (NSF) is a rare disease that occurs mostly in people with kidney disease after exposure to gadolinium-based contrast agents (GBCAs). Gadolinium is a substance found in contrast dye. Healthcare providers use contrast dye during imaging tests like magnetic resonance imaging (MRI). Having kidney damage puts you at risk for NSF because your kidneys have trouble filtering GBCAs from your bloodstream.

NSF causes your skin to become thick, hard or begin to swell and itch. It can lead to joint contracture, which is when your muscles and tendons become stuck in a bent or straightened position. NSF can also affect other parts of your body like your heart and lungs because it causes the tissue and muscles in your chest to harden. There’s currently no treatment for NSF that can stop its progression or reverse its effects.

The U.S. Food & Drug Administration (FDA) requires warning labels on certain GBCAs that say the product shouldn’t be given to people with kidney disease because it’s a known cause of NSF. The newer GBCAs on the market aren’t known to cause NSF in people with kidney disease.

How common is nephrogenic systemic fibrosis?

It’s an incredibly rare disease. There haven’t been any new cases of NSF in over 10 years. The prevalence went down significantly after 2006 when the healthcare community became aware of how GBCAs affect people with kidney issues.

What are the symptoms of nephrogenic systemic fibrosis?

You can develop symptoms of nephrogenic systemic fibrosis (NSF) as early as the day of exposure to gadolinium-based contrast agents, or up to several months later. In one study, 50% of people had symptoms within 12 days of exposure.

Symptoms of NSF include:

• Swelling, tightening and hardening of your skin. This occurs mostly on your arms, legs and trunk area. It rarely affects your face.
• Darkened bumps or patches on your skin. Your skin may eventually dimple and resemble an orange peel.
• Itchy, burning or painful skin.
• Being unable to move your muscles and joints as you typically can. This is due to your skin thickening and swelling.

Some people have symptoms that affect their internal organs and muscles. These symptoms can cause:

• Extreme muscle weakness.
• Loss of range of motion (how far you can bend and straighten your arms, legs, etc.) due to your muscles tightening.

Fibrosis can progress and cause hardened deposits in your muscles, lungs, esophagus, eyes and heart. This can impact how well these organs work. It can cause long-term and permanent disability and be fatal in some people.

What causes nephrogenic systemic fibrosis?

Most cases of nephrogenic systemic fibrosis occur after exposure to gadolinium-based contrast agents (GBCA). Exposure occurs when the chemical gadolinium is used to enhance images during an MRI. Exactly how gadolinium leads to nephrogenic systemic fibrosis is unclear. But, it’s clear that there’s a link between kidney disease and GBCAs. It also appears that your risk goes up more if you’re given higher amounts of gadolinium or if your healthcare provider used certain GBCAs.

Nephrogenic systemic fibrosis most often happens to people with chronic kidney disease (CKD) or those on dialysis.

There haven’t been any new reports of NSF in almost 15 years. This is due to the development and use of more stable, less toxic GBCAs. Limiting the use of gadolinium in people with kidney disease also played a role. The FDA advises against using older GBCAs in people with kidney disease or a kidney injury.

What are the risk factors for nephrogenic systemic fibrosis?

The main risk factor for developing NSF is having kidney disease or some other kidney function impairment. This includes having prior kidney surgery, kidney transplant or having a single kidney. Other conditions like blood clotting problems or infection may further increase your risk of NSF if you have kidney disease.

Healthcare providers are now aware of the harmful effects older GBCAs have on people with reduced kidney function. Your risk is much lower now that preventive measures are in place.

What are the complications of nephrogenic systemic fibrosis?

Complications of NSF can be severe and fatal. Noticing your skin is tight or hard is usually the first sign. But, as the condition worsens, the hardening can affect your internal organs and muscles. For example, your muscles and joints could become so stiff and unmovable that you’re unable to walk. If NSF affects your lungs or heart, it can cause breathing problems or impair your heart’s ability to pump blood.

How is nephrogenic systemic fibrosis diagnosed?

The only way to be certain you have NSF is to have a skin biopsy. During a skin biopsy, a healthcare provider removes a sample of your skin and sends it to a lab for analysis. A provider would most likely only order this test if they had reason to believe you may have NSF based on your health history and a physical exam.

How is nephrogenic systemic fibrosis treated?

Currently, there are no approved treatments for NSF. There are limited studies on treatments for NSF since the disease is rare. But, the following treatments have been shown to help certain people with NSF:

• Dialysis can remove gadolinium from your body after an MRI. This can be helpful for people with chronic kidney disease, but there’s no evidence that this will stop you from developing NSF.
• Physical therapy may help preserve your range of motion and flexibility.
• Kidney transplants could be an option in people with NSF.

If you have kidney disease, it’s best to avoid exposure to gadolinium. But there may be situations when gadolinium is necessary to get the best images from an MRI. Healthcare providers should weigh the benefit of the MRI against the potential risk of gadolinium exposure. If your provider orders an MRI with contrast agents and you have kidney problems, ask them if you’re at risk for NSF.

Can nephrogenic systemic fibrosis be prevented?

Avoiding older GBCAs in people with kidney disease is the best way to prevent NSF. Using newer GBCAs is safer and less toxic to people with kidney conditions.

The FDA recommends against using gadolinium-based contrast agents in people with certain kidney conditions unless there are no other options.

For people with normal kidney function, there doesn’t appear to be any risk of using GBCAs.

What is the mortality rate of nephrogenic systemic fibrosis?

Prior to 2019, the FDA reported 3,094 total cases of NSF, including 742 deaths. But there haven’t been any new cases in over 10 years. This is mainly because the FDA and healthcare community are aware of the effects of GBCA on people with kidney disease.

When should I see my healthcare provider?

Contact your healthcare provider if you have kidney disease and notice any of the following symptoms as they could be signs of NSF:

• Hardening or thickening of your skin.
• Itchy or burning skin.
• Red or darkened patches on your skin.

A note from Cleveland Clinic

With preventive measures in place, you’re unlikely to get a diagnosis of NSF. But if you have kidney disease and require an MRI, talk to your healthcare provider about NSF and your risk. While newer GBCAs aren’t toxic and appear safe, sharing your health history with your provider and discussing your risk is always a good practice.