Nephrogenic Systemic Fibrosis (NSF)

Overview

What is nephrogenic systemic fibrosis?

Nephrogenic systemic fibrosis (NSF) is a rare disease that can affect different parts of the body. It most commonly first appears as swelling or itching of the skin. It can lead to thickening or hardening of the skin and deposits in other parts of the body.

The disease was first observed in 1997, and was thought to only affect the skin. Only later was the risk to other organs recognized.

Although the condition was first seen in patients with severe kidney problems (often people who were on dialysis), only a small minority of patients were affected. These patients often had other problems that could lead to inflammation in the body, such as recent major surgery, blood clot, cancer or infection.

Nephrogenic systemic fibrosis may be a progressive condition. As it gets worse, it can go well beyond the skin and cause multiple organs to fail. It can be fatal.

Symptoms and Causes

What causes nephrogenic systemic fibrosis?

Most, if not all, cases of nephrogenic systemic fibrosis are caused by exposure to gadolinium-based contrast agents (GBCA). Exposure occurs when the chemical element gadolinium is used to enhance images gathered in magnetic resonance imaging (MRI).

Nephrogenic systemic fibrosis occurs in patients who have acute kidney injury (AKI), chronic kidney disease (CKD) or those on dialysis (ESRD). Additional patients at risk include those with diabetes mellitus, hypertension, kidney transplant, a single kidney or history of kidney surgery.

There have been reports of patients who have not been exposed to gadolinium in an MRI developing nephrogenic systemic fibrosis. However, most of those patients have in fact been exposed to gadolinium in one way or another, such as in another test or a surgery, an injury or an infection.

About 4% of patients with severe kidney problems will develop nephrogenic systemic fibrosis after exposure to gadolinium. About 30% of cases are reported to be fatal but that number could be much higher as the condition is often misdiagnosed or not reported accurately because it is not well understood.

Gadolinium has been used since the late 1980s. Exactly how gadolinium leads to nephrogenic systemic fibrosis is unclear. However, it does appear that the risk of developing the condition goes up as a person is exposed to certain types called linear gadolinium and as a higher amount of gadolinium is given.

Since 2009, no new cases of NSF have been reported. This finding reflects the use of more stable, less toxic gadolinium agents and limiting the use of gadolinium in patients with renal failure. Agents that are macrocytic are much less toxic. As a result, the safe use of gadolinium and avoidance of fibrosis has increased.

What are the symptoms of nephrogenic systemic fibrosis?

Patients can develop symptoms of nephrogenic systemic fibrosis as early as the day they are exposed to gadolinium-based contrast agents, or up to several months later. In one study, 50% of patients had symptoms within 12 days after exposure. The likelihood of a patient developing NSF differs after exposure to different formulations of GBCAs and as a higher amounts of gadolinium are given.

  • Early symptoms tend to be itchy, red bumps that may be hard. These bumps may gather to form a dimply appearance that can resemble an orange peel. The bumps are most common on the arms and legs, as well as the torso. They rarely affect the face.
  • Patients also can develop pain in their joints that can become disabling. This can be followed by hardening and thickening of the skin especially over the arms, legs and trunk.
  • Fibrosis can progress with deposits in the muscles, lungs, esophagus and heart that damage these organs. This condition can be fatal.

Diagnosis and Tests

How is nephrogenic systemic fibrosis diagnosed?

The only way to be certain is to have a deep skin biopsy (where tissue is taken for microscopic examination). A doctor would most likely only order such a test if he or she had reason to believe the patient may have nephrogenic systemic fibrosis.

Management and Treatment

How is nephrogenic systemic fibrosis treated?

Currently, there are no effective treatments. Dialysis can remove gadolinium from the body after an MRI, but there is no evidence that this stops patients from developing nephrogenic systemic fibrosis. Therefore, patients already on dialysis should undergo a dialysis session right after being given gadolinium for an MRI, but starting dialysis for this purpose is not recommended.

Avoiding exposure of at-risk patients to gadolinium is the best practice but there may be situations when gadolinium must be given to obtain the best information from an MRI.

We recommend giving intravenous fluids to patients at risk who still make urine and using the low-risk gadolinium compounds. MRIs using gadolinium contrast can be ordered for many reasons, including to look for possible masses in the skull, study the blood vessels throughout the body, look for malignancies and evaluate unknown masses in the body. Patients who have certain kidney problems should not undergo these tests unless there is no other way to diagnose a problem.

GBCAs can provide crucial, life-saving medical information. Each time a gadolinium-enhanced MRI study is considered, doctors should weigh the benefit of the MRI against the potential risk of gadolinium deposition for each individual patient.

If your physician orders an MRI with contrast agents and you have kidney problems, ask him or her if you are at risk for nephrogenic systemic fibrosis. If so, ask what alternative tests are available for you.

Prevention

Can nephrogenic systemic fibrosis be prevented?

For patients with normal kidney function, there does not appear to be any risk. Patients with kidney disease whose eGFR is below 30 ml/min/1.73 m2 are at increased risk. Only one patient has been reported to develop NSF with kidney function better than this. Patients on dialysis who require gadolinium, studies have shown that performing dialysis immediately after gadolinium-based MRI can help reduce the chances of developing nephrogenic systemic fibrosis.

The U.S. Food and Drug Administration recommends against using gadolinium-based contrast agents in patients with certain kidney problems unless there are no other options. Other imaging methods should be used on these patients if possible.

The risk for gadolinium-related damaged is less if we use the lowest dose necessary, avoid repeat doses, and only use the safer macrocytic types of gadolinium.

Last reviewed by a Cleveland Clinic medical professional on 04/18/2018.

References

  • American Family Physician. Accessed 5/10/2018.Gadolinium-Associated Nephrogenic Systemic Fibrosis. (http://www.aafp.org/afp/2009/1001/p711.html)
  • National Institutes of Health Genetic and Rare Diseases Information Center. Accessed 5/10/2018.Nephrogenic Systemic Fibrosis. (https://rarediseases.info.nih.gov/diseases/9725/nephrogenic-systemic-fibrosis#ref_237)
  • National Organization for Rare Disorders. . Accessed 5/10/2018.Nephrogenic Systemic Fibrosis (https://rarediseases.org/rare-diseases/nephrogenic-systemic-fibrosis)
  • J. Ramalho, R.C. Semelka, M. Ramalho, et al. Gadolinium-Based Contrast Agent Accumulation and Toxicity: An Update. American Journal of Neuroradiology July 2016, 37 (7) 1192-1198.

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