Nephrogenic Systemic Fibrosis (NSF)

What causes NSF

NSF was first described in the late 1990s and linked to gadolinium-based contrast agents (GBCAs) in 2006. Gadolinium helps MRI scans show blood vessels and tissues. It is normally removed quickly by the kidneys. When the kidneys work very poorly, gadolinium stays in the body much longer. Some older agents, mainly "linear" types, release free gadolinium more easily. Free gadolinium is thought to deposit in tissues and trigger cells that produce excess collagen and scar-like fibrosis.

Risk factors

• severe chronic kidney disease, with eGFR below 30 mL/min/1.73 m²
• dialysis
• acute kidney injury
• higher or repeated doses of older, higher-risk gadolinium agents
• inflammation, recent surgery or blood clots may contribute

NSF has not been seen in people with normal kidney function.

Symptoms

Symptoms usually begin days to months after gadolinium exposure, occasionally longer.

Skin

• swelling of the hands, feet, legs and arms
• reddened or darkened patches that become thick, hard and tight, sometimes with a "woody" or orange-peel texture
• burning, itching or sharp pain
• usually starting on the lower legs and moving up, and rarely affecting the face

Joints and muscles

• stiffness and reduced movement as skin and deeper tissues harden
• contractures that fix the hands, elbows, knees or ankles in a bent position
• muscle weakness
• difficulty walking, and in severe cases wheelchair dependence

Eyes and organs

• yellow plaques on the whites of the eyes
• fibrosis of internal organs, including the heart, lungs, diaphragm, liver and muscles, which can be life-threatening in severe cases

Diagnosis

Diagnosis combines:

• a history of kidney disease and gadolinium exposure
• typical skin and joint findings
• a deep skin biopsy showing thickened collagen and specific spindle-shaped cells
• sometimes measurement of gadolinium in tissue

NSF must be distinguished from scleroderma, morphea, eosinophilic fasciitis, lipodermatosclerosis and other causes of skin thickening. Unlike scleroderma, NSF usually spares the face and does not cause Raynaud's phenomenon or the autoantibodies typical of scleroderma.

Treatment

There is no proven cure. Options include:

• improving kidney function: recovery from acute kidney injury or a successful kidney transplant can halt progression and sometimes partly reverse skin changes
• physical therapy: daily stretching and range-of-motion exercises to prevent contractures and maintain mobility
• pain control for burning and joint pain
• therapies with limited evidence: extracorporeal photopheresis, ultraviolet light therapy, imatinib, sodium thiosulfate, plasma exchange and others, used case by case
• dialysis soon after gadolinium exposure in people already on dialysis to help remove the contrast, although proof that this prevents NSF is limited

Prevention

NSF is now very rare because of changes in practice:

• screening kidney function (eGFR) before contrast MRI in at-risk patients
• using group II gadolinium agents, which are considered very low risk, at the lowest effective dose
• avoiding gadolinium in severe kidney disease unless the information is essential and cannot be obtained otherwise
• considering non-contrast MRI or other imaging
• coordinating dialysis timing for people on dialysis

If you have kidney disease and need an MRI, tell the radiology team. With modern agents, the risk is extremely low, and needed scans should not be avoided out of fear.

Outlook

The course varies. Some people have mild disease that stabilizes. Others have progressive skin and joint involvement causing severe disability. Internal organ involvement can be fatal. Improvement of kidney function offers the best chance of stabilization or improvement.

Frequently asked questions

What is nephrogenic systemic fibrosis?

NSF is a rare disease in which the skin and connective tissues become thick and hard, and joints can become stiff and fixed. It occurs in people with severe kidney disease after exposure to certain gadolinium contrast agents used in MRI.

Is gadolinium safe if I have kidney disease?

For most people with mild to moderate kidney disease, modern group II gadolinium agents are considered very low risk. For people with severe kidney disease or on dialysis, doctors weigh benefits and risks, use the safest agent at the lowest dose, and consider alternatives.

Can NSF be cured?

There is no reliable cure. Improving kidney function, particularly with a kidney transplant, can stop progression and sometimes improve symptoms. Physical therapy helps preserve mobility, and other treatments are tried case by case.

Can people with normal kidneys get NSF?

NSF has essentially not been reported in people with normal kidney function. The kidneys clear gadolinium quickly when they work well, preventing buildup in tissues.