Nephrogenic Systemic Fibrosis – Symptoms and Causes

Overview

Nephrogenic systemic fibrosis is a rare condition that primarily affects individuals with severe kidney failure. The disease typically causes skin thickening and darkening over extensive areas, resembling conditions like scleroderma.

The condition has been strongly linked to the use of older gadolinium-based contrast agents during MRI imaging in people with impaired kidney function.

Beyond skin changes, this disorder can impact internal organs, including the heart and lungs. Many patients develop joint contractures—a painful condition where muscles and tendons shorten, limiting movement and causing disability.

Symptoms

Nephrogenic systemic fibrosis can develop anywhere from days to years after exposure to older gadolinium-based contrast agents. The condition presents with several noticeable skin changes and other symptoms.

Skin-related symptoms include:

• Swelling and skin tightening
• Red or dark patches on the skin
• Hardened, thickened skin (typically on arms and legs, rarely on face)
• Skin with a “woody” texture or orange-peel appearance
• Burning sensations, itching, or sharp pains
• Limited movement due to skin thickening
• Occasional blisters or ulcers

Beyond skin symptoms, some people experience:

• Weakness in muscles
• Limited joint movement from muscle contractures in extremities
• Pain in bones, particularly hips or ribs
• Reduced function in internal organs (heart, lungs, diaphragm, digestive system, liver)
• Yellow plaques on the white part of the eyes (sclera)

The condition tends to be long-lasting. While some patients see improvement over time, others may develop severe disability. In rare cases, nephrogenic systemic fibrosis can be fatal.

Causes

The development of nephrogenic systemic fibrosis (NSF) is not completely understood by medical experts. This condition involves the formation of fibrous tissue in the skin and other connective tissues, creating scarring throughout the body.

Research has identified a strong link between NSF and older gadolinium-based contrast agents (group 1) used during MRI scans, especially earlier-generation types in people with kidney problems.

When kidney function is impaired, these substances remain in the bloodstream longer because the kidneys cannot effectively remove them.

Risk Factors

While the connection between these contributing factors and NSF is not fully understood, ongoing research suggests they may interact with impaired kidney function to trigger the disease process.

The risk is significantly higher in patients with:

• Moderate to severe kidney disease
• Kidney transplant recipients with impaired kidney function
• Individuals undergoing hemodialysis or peritoneal dialysis
• Patients experiencing acute kidney injury

Additional factors may further increase the risk of NSF when combined with kidney disease and gadolinium exposure. These include:

• High-dose erythropoietin (EPO) treatment for anemia
• Recent vascular surgery
• Blood clotting disorders
• Severe infections

NSF typically involves the skin and the tissues just beneath it, but it can also cause scarring and thickening in internal organs and other soft tissues throughout the body.

Prevention

To prevent nephrogenic systemic fibrosis, doctors recommend avoiding older Group 1 gadolinium-based contrast agents. Newer Group 2 contrast agents offer a safer alternative with no increased risk.

Medical professionals now use these safer contrast materials during MRI procedures for patients with kidney problems.