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Nephrogenic systemic fibrosis (NSF) is an uncommon disorder of the organs and skin that predominantly affects people with severe kidney disease. The disease develops when patients have negative reactions to the contrast dyes used in imaging scans such as magnetic resonance imaging or MRIs. These tests require injections that enable the doctor to evaluate the scans, but repeated injections of the dye agent gadolinium can cause thickening of the skin and underlying tissues (fibrosis) with the formation of firm nodules and hardening of skeletal muscles.

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What is Gadolinium?

Gadolinium is a metallic element used in gadolinium-based contrast agents (GBCA). The rare earth metal can be converted to an injectable solution given intravenously to a patient prior to an imaging scan. According to the FDA, GBCAs clarify, contrast, and provide detailed images of MRI kidney scans. People with severe renal insufficiency cannot eliminate gadolinium from the body. One study found that after gadolinium enters the bloodstream, the substance goes to the brain and remains there, instead of being removed through urination. Currently, the health implications of gadolinium remaining in the brain are unclear.

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Are There Alternatives to Gadolinium-Based Contrast Agents?

About half of all MRIs use a GBCA to enhance diagnostic imaging scans. In addition to monitoring severe kidney insufficiency, the dyes are used during MRIs that scan brain injuries, liver inflammation, circulatory disorders, and inflammatory joint disease. In 2017, the FDA put warnings on GBCA products that recommend people with adequately functioning kidneys should not stop having MRI scans using GBCA dyes, as no studies indicate GBCA is detrimental to these individuals. Additionally, a gadolinium contrast agent is not always necessary when performing MRI scans. Whether one is necessary is a topic to discuss with a physician.

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Why Does GBCA Cause Nephrogenic Systemic Fibrosis?

Nephrogenic systemic fibrosis (NSF) is an uncommon disorder of the organs and skin that predominantly affects people with severe kidney disease. The disease develops when patients have negative reactions to the contrast dyes used in imaging scans such as magnetic resonance imaging or MRIs. These tests require injections that enable the doctor to evaluate the scans, but repeated injections of the dye agent gadolinium can cause thickening of the skin and underlying tissues (fibrosis) and hardening of skeletal muscles. Conditions causing inflammatory reactions, such as infections, major surgeries, or thrombosis, could induce NSF symptoms as increased collagen production attempts to fight systemic tissue inflammation.

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Symptoms of NSF

Signs of NSF often emerge within a few weeks of exposure to GBCA. Symptom severity and progression depends on a person's ability to properly eliminate the substance from their body. Early signs of NSF are

  • Dark patches of skin, papules, that develop on the arms and legs. Papules are more commonly seen on the upper arms, wrists and below the thighs
  • Fluid retention and swelling (edema)
  • Itchy, red skin
  • Shiny patches of skin

Advanced symptoms of NSF include

  • Wrinkled, thick, reddish-orange patches of skin
  • Yellowing of the eyes
  • Muscle weakness
  • Induration (skin hardening) that may reduce joint flexibility and cause pain during movement
  • In severe cases, the person may eventually need to use a wheelchair. Joints may become so rigid they can no longer be moved, remaining in a permanently straight or bent position.
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Treatment for NSF

Doctors recommend supportive treatments such as physical therapy and pain medications for treating nephrogenic systemic fibrosis. The former helps preserve functionality and prevent joint contractures and rigidity. Plasmapheresis is a newer treatment that is similar to dialysis but involves a kidney transplant. By filtering the blood and removing antibodies in plasma that might cause rejection of the kidney, doctors can make it safe for a person to undergo a kidney transplant from donors with incompatible blood types. Plasmapheresis reduces the time it takes to find an appropriate kidney donor by removing the problems associated with incompatibility. Intravenous immunoglobulin therapy and immune modulators may also help reduce or delay symptoms of NSF. Immunoglobulins are special antibodies that suppress cytokines and other inflammatory mediators responsible for the systemic inflammation seen in people with NSF. Phototherapy, exposing the skin to ultraviolet light (UVA rays), may also help the skin manifestations of NSF. All of these treatments are considered experimental, as there is no proven treatment for NSF.

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Can Children Develop NSF?

Nephrogenic systemic fibrosis in children is rare, though there are a few cases in babies who receive GBCA due to having immature kidneys or congenital heart disease. However, many babies and young children requiring MRI scans with GBCA do not develop signs of NSF. Researchers speculate that infants may have some resistance to GBCA, perhaps relating to their immature immune systems and lack of inflammatory response.

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Diagnosing NSF

Diagnosis of nephrogenic systemic fibrosis involves assessing visible symptoms. The doctor will also perform a histological examination of skin biopsies and determine the degree of GBCA exposure. NSF symptoms mimic those of other conditions, and the doctor will also test for these. People with limited exposure to GBCA may have another skin disorder like systemic sclerosis, cellulitis, or eosinophilic fasciitis that presents symptoms similar to NSF.

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Who is Most at Risk for NSF?

People undergoing regular peritoneal or kidney dialysis have a higher risk of NSF than those who do not yet need dialysis. Also, individuals getting GBCA injections after serious kidney injuries due to an accident may be at risk if they do not receive kidney dialysis before the injections. The likelihood of developing NSF increases as kidney function decreases, dependent on the individual's exposure to GBCA.

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Complications of NSF

In addition to reduced flexibility and painful thickening of the skin, NSF may target organ tissue, specifically the heart or lungs. Thickening and hardening of the tissues around these organs can inhibit breathing and interfere with normal heart rhythms. Organ failure due to NSF is rare but can affect people with severe kidney disease who need numerous MRIs. Fractures and breaks are additional complications of NSF. People with reduced joint flexibility are prone to stumbling and falling as NSF progresses. If the skin around the knee and hip joints thicken and harden enough to inhibit movement, the individual should use a walking aid to prevent injury.

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Preemptive Kidney Transplants to Avoid NSF

A preemptive kidney transplant means individuals with renal insufficiency or failure receive their transplant before beginning dialysis. Getting a kidney transplant soon after kidneys start failing is called an early transplant. These types of transplants may prevent NSF from worsening if MRIs using GBCA are a necessary part of treatment. Kidney patients should talk with their physicians about the risks of NSF and whether it would be in their best interest to consider an early transplant.

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Disclaimer

This site offers information designed for educational purposes only. You should not rely on any information on this site as a substitute for professional medical advice, diagnosis, treatment, or as a substitute for, professional counseling care, advice, diagnosis, or treatment. If you have any concerns or questions about your health, you should always consult with a physician or other healthcare professional.