Definition

What is nephrogenic systemic fibrosis (NSF)?

Nephrogenic systemic fibrosis (NSF) occurs in some individuals with reduced kidney function, who have been exposed to an intravenous contrast material that contains gadolinium. A contrast material is a dye that is sometimes used during magnetic resonance imaging (MRI). The term, fibrosis, refers to the thickening and scarring of connective tissue, most often the consequence of inflammation or injury. NSF is characterized by thickening and hardening (fibrosis) of the skin, subcutaneous tissues, and, sometimes, underlying skeletal muscle. The arms and legs are most often affected. In some cases, the skin on the trunk can also become involved. This proliferation of fibrotic tissue may become systemic, extending to other areas including the smooth, delicate membrane that surrounds the lungs (pleura), the sac surrounding the heart (pericardium), the thin sheet of muscle that aids respiration by moving up and down when breathing (diaphragm), and the outermost layer (dura mater) of the three membranes covering the brain and spinal cord.

NSF was thought to predominantly involve the skin and was originally referred to as nephrogenic fibrosing dermopathy. However, it is now known that it may involve several internal organs (systemic disorder), potentially leading to a progressive and severe disease course. NSF has not been reported in individuals with normal kidney function.

How common is nephrogenic systemic fibrosis (NSF)?

Nephrogenic systemic fibrosis (NSF) is a rare disorder. Please discuss with your doctor for further information.

Symptoms

What are the symptoms of nephrogenic systemic fibrosis (NSF)?

Nephrogenic systemic fibrosis can begin days to months after exposure to gadolinium-containing contrast, but progresses quickly. Some signs and symptoms of nephrogenic systemic fibrosis may include:

  • Swelling and tightening of the skin
  • Thickening and hardening of the skin, typically on the arms and legs and sometimes on the body, but almost never on the face or head
  • Skin that may feel “woody” and develop an orange-peel appearance and darkening (excess pigmentation)
  • Burning, itching or severe sharp pains in areas of involvement
  • Skin thickening that inhibits movement, resulting in loss of joint flexibility
  • Rarely, blisters or ulcers

In some people, involvement of muscles and body organs may cause:

  • Muscle weakness
  • Limitation of joint motion caused by muscle tightening (contractures) in arms, hands, legs and feet
  • Bone pain
  • Reduced internal organ function, including heart, lung, diaphragm, gastrointestinal tract, or liver, but direct evidence is often lacking
  • Yellow plaques on the white surface (sclera) of the eyes
  • Blood clots

The condition is generally long term (chronic), but some people may improve. In a few people, it can cause severe disability, even death.

There may be some symptoms not listed above. If you have any concerns about a symptom, please consult your doctor.

When should I see my doctor?

If you have any signs or symptoms listed above or have any questions, please consult with your doctor. Everyone’s body acts differently. It is always best to discuss with your doctor what is best for your situation.

Causes

What causes nephrogenic systemic fibrosis (NSF)?

The exact underlying cause of NSF is not fully understood. The disorder occurs in individuals with advanced kidney disease who have been exposed to gadolinium-based contrasts agents that are used in magnetic resonance imaging.

Gadolinium is a heavy metal with paramagnetic qualities that cause it to respond differently within a magnetic field. Because of this trait, gadolinium has been used for magnetic resonance imaging examinations. Gadolinium is considered toxic and, in order to be used in contrast dyes, is bound to other molecules to facilitate its passage through the body. Gadolinium contrast agents are ultimately excreted through the kidneys. Individuals with impaired kidney function cannot adequately and quickly eliminate GBCA from the body. Researchers believe this prolonged excretion may lead to a breakdown of the contrast chemical, with release of the Gadolinium atom (dechelation). This foreign material may then lead to a process resembling a chronic wound healing reaction, with abundant production of collagen.

In addition to kidney disease and exposure to GBCAs, individuals with NSF may have a “proinflammatory” state, which refers to any condition that causes an inflammatory reaction in the body. In individuals who had developed NSF, this has included recent major surgery, infection, malignancy or the formation of blood clots (thrombosis). Many individuals with NSF have had recent vascular surgery or a thrombotic condition before the onset of the disorder. The exact relationship between these inflammatory conditions and risk for development of NSF is not known.

Researchers have also detected the presence of “circulating fibrocytes” (CFs) in the skin of individuals with NSF. CFs are circulating cells that respond to tissue damage by exiting the circulation and maturing into cells that produce fibrous tissue (collagen). They are normally participants in the wound healing process. Researchers believe that these cells are inappropriately summoned to the skin in great numbers, despite the lack of an obvious injury. Currently investigators suspect the dechelation event allows the CFs to home to the skin, where they produce the abundant collagen typical of NSF. The precise details of this process are not fully understood and require further study.

Risk factors

What increases my risk for nephrogenic systemic fibrosis (NSF)?

There are many risk factors for nephrogenic systemic fibrosis (NSF), such as:

  • Have moderate to severe kidney disease
  • Have had a kidney transplant, but have compromised renal function
  • Are receiving hemodialysis or peritoneal dialysis
  • Have acute kidney injury

Diagnosis & treatment

The information provided is not a substitute for any medical advice. ALWAYS consult with your doctor for more information.

How is nephrogenic systemic fibrosis (NSF) diagnosed?

  • Physical exam for signs and symptoms of the disease, and evaluation for a possible history of MRI using gadolinium when advanced kidney failure is present
  • A sample of tissue (biopsy) taken from the skin and muscle
  • Other tests as needed that may indicate involvement of muscles and internal organs

How is nephrogenic systemic fibrosis (NSF) treated?

There is no cure for nephrogenic systemic fibrosis, and no treatment is consistently successful in halting or reversing the progression of the disease. Nephrogenic systemic fibrosis only occurs rarely, making it difficult to conduct large studies.

Mayo Clinic doctors have experience with the following treatments for nephrogenic systemic fibrosis. More research is needed to determine if these treatments help, but they have shown limited success in some people:

  • In people with severely reduced kidney function, performing hemodialysis immediately after receiving gadolinium-containing contrast may decrease the possibility of nephrogenic systemic fibrosis.
  • Physical therapy. Physical therapy that helps stretch the involved limbs may help slow the progression of joint contractures and preserve movement.
  • Kidney transplant. For people who are appropriate candidates, improvement in renal function because of a kidney transplant may help improve nephrogenic systemic fibrosis over time.
  • Ultraviolet A phototherapy. Exposure of the skin to ultraviolet A light may reduce the skin thickening and hardening, but it’s unclear if the treatment penetrates deeply enough into the skin to be effective.
  • Extracorporeal photopheresis. This treatment involves drawing the blood outside the body and treating the blood with a drug that sensitizes it to ultraviolet light. The blood is then exposed to ultraviolet light and returned to the body. Some people have shown improvement after receiving this therapy.
  • This procedure involves removing unwanted substances from the blood by separating solid blood cells from plasma, replacing plasma with donor plasma or albumin, then mixing it with the original solid blood cells and returning it to the body.

These medications have been shown to help some people, but side effects limit their use:

  • Pentoxifylline (Pentoxil). There is limited success with this medication, which theoretically decreases the thickness and stickiness (viscosity) of blood, aiding circulation.
  • Imatinib (Gleevec). Although this treatment shows some promise in reducing skin thickening and tightening, more research is needed.
  • Sodium thiosulfate. Possible benefit has been shown using this medication, but more research is needed.

Lifestyle changes & home remedies

What are some lifestyle changes or home remedies that can help me manage nephrogenic systemic fibrosis (NSF)?

Please discuss with your doctor for further information.

If you have any questions, please consult with your doctor to better understand the best solution for you.

Hello Health Group does not provide medical advice, diagnosis or treatment.

Sources

Review Date: November 24, 2017 | Last Modified: November 24, 2017

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