New study suggests cause of debilitating skin condition

September 24, 2007

WINSTON-SALEM, N.C. - New findings from researchers at Wake Forest University Baptist Medical Center and colleagues suggest why some people with kidney failure can develop a rare tightening and swelling of the skin and other organs, including the lungs and heart.

Reporting in the October issue of the American Journal of Dermatopathology, the authors suggest a possible explanation for why some patients on kidney dialysis who are injected with a "contrast agent" during a magnetic resonance imaging (MRI) develop nephrogenic systemic fibrosis (NSF).

The U.S. Food and Drug Administration now requires a warning about the potential risk on the products' labels. NSF leads to thickened, rough or hard skin usually on the arms, legs or trunk. In some cases, the limbs can become difficult or even impossible to move.

"The cause of this syndrome has been unclear," said David C. Sane, M.D., senior researcher on the project. "Our research suggests both a potential cause and the possibility of preventing or treating NSF."

Sane said the finding - that an enzyme known as transglutaminase-2 (TG2) may be involved - is the first to suggest how exposure to contrast agents may lead to NSF.

It has not been known what causes NSF, but a risk factor is exposure to gadolinium, an agent injected into patient's veins during some MRI procedures to help improve the visibility of internal organs during the test. The condition is relatively rare - it occurs in about 2 percent to 4 percent of kidney patients on dialysis who are exposed to gadolinium.

The researchers tested the hypothesis that TG2 may be involved in the response. The enzyme is found throughout the body and is involved in blood clotting and wound healing. They hypothesized that gadolinium may activate the enzyme and cause NSF.

The group obtained skin biopsies from five people with NSF and three healthy people. All NSF patients had renal failure and had previously had imaging procedures using gadolinium. The researchers tested for the presence of TG2 in the skin samples.

"Compared to the healthy subjects, there was a marked increase in TG2 in the subjects with NSF," said Sane. "This suggests that activation of TG2 can produce the syndrome. TG2 is expressed in virtually all tissues and may explain why the fibrosis can occur in the heart and lungs, as well as the skin."

Sane said the results also suggest a strategy for preventing or treating NSF - drugs such as cysteamine that inhibit the activation of TG-2.

"Our research is a pilot study, but we believe the results warrant further research into the use of TG-2 inhibitors in the treatment and prevention of NSF," said Gil Yosipovitch, M.D., co-senior researcher, and a dermatologist. "Solving this puzzle might allow dialysis patients to take full advantage of the diagnostic capabilities of MRI."

"This could be a general mechanism for a broad range of disorders that involve fibrosis, or tissue thickening," said Sane.
-end-
Other researchers were lead investigator Amy Parsons, M.D., Daniel Sheehan, M.D., and Omar P. Sangueza, M.D., all from Wake Forest's Department of Pathology, and Charles S. Greenberg, M.D., with Duke University.

Media Contacts: Karen Richardson, krchrdsn@wfubmc.edu, or Shannon Koontz, shkoontz@wfubmc.edu, 336-716-4587.

Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. The system comprises 1,154 acute care, psychiatric, rehabilitation and long-term care beds and is consistently ranked as one of "America's Best Hospitals" by U.S. News & World Report.

Wake Forest Baptist Medical Center

Related Dialysis Articles from Brightsurf:

Immediate dialysis no better than wait-until-necessary approach, researchers find
In the largest international study of its kind, researchers at the University of Alberta and Toronto's St.

Predictors of 5-year mortality in young dialysis patients
The analysis published in NDT [1] evaluated for the first time the association of a large number of demographic, HD treatment and laboratory variables with mortality in patients on chronic hemodialysis treatment since childhood.

COVID-19 mortality alarmingly high in dialysis patients
Analysis of a Spanish experience shows that COVID-19 is frequent in hemodialysis patients, who appear to be at risk for worse outcome.

Survival following switch from urgent in-center hemodialysis to home dialysis
Few patients who start urgent and unplanned dialysis in clinical centers switch to home dialysis.

Is ownership of dialysis facilities associated with access to kidney transplants?
An analysis that included data for nearly 1.5 million patients with end-stage kidney disease looked at whether ownership of dialysis facilities was associated with patients' access to kidney transplants.

At-home dialysis improves quality of life
The rate of people starting voluntary at-home peritoneal dialysis rose from 15% to 34% over 10 years at Kaiser Permanente in Northern California, providing a convenient and safe way to manage advanced-stage kidney disease compared with center-based hemodialysis, according to research published today in JAMA Internal Medicine.

Hydration sensor could improve dialysis
Researchers from MIT and Massachusetts General Hospital have now developed a portable sensor that can accurately measure patients' hydration levels using a technique known as nuclear magnetic resonance (NMR) relaxometry.

Uncovering possible role of polyphosphate in dialysis-related amyloidosis
Researchers from Osaka University found that the low concentrations of the naturally occurring biopolymer, polyphosphate (polyP), induces amyloid formation from β2 microglobulin under both acidic and neutral conditions but by different mechanisms.

Study compares dialysis reimbursement around the globe
Dialysis reimbursement policies in most countries are focused on conventional in-center hemodialysis, although home hemodialysis and peritoneal dialysis might contribute to quality of life and cost savings.

Elderly patients on dialysis have a high risk of dementia
Older kidney disease patients who are sick enough to require the blood-filtering treatment known as dialysis are at high risk of dementia, including Alzheimer's disease, according to a study led by scientists at Johns Hopkins Bloomberg School of Public Health.

Read More: Dialysis News and Dialysis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.