Higher death rates in kidney patients with newly recognized disease

September 28, 2007

Nephrogenic systemic fibrosis (NSF) is a newly identified debilitating and painful condition that affects patients with kidney failure and is characterized by a thickening and hardening of the skin. It usually affects the arms and legs but it can also affect internal organs and can progress so rapidly that patients can be immobilized and wheelchair-bound within a few weeks. Although it is not clear what causes NSF, the condition has been linked to gadolinium, a contrast agent used in MRI scans. A new study published in the October issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis) on the prevalence of NSF and its risk factors found that the disease is associated with an increased risk of dying and that gadolinium exposure is a significant risk factor for developing it.

Led by Jonathan Kay of the Massachusetts General Hospital in Boston, MA, Derrick J. Todd, Anna Kagan, and Lori B. Chibnik conducted a study on patients undergoing dialysis at six outpatient centers in the Boston area. They used a simple three-part skin examination to check for the three skin changes associated with NSF: hyperpigmentation (darkening of the skin), hardening and tethering (thickening). Patients with two out of the three findings were considered to have a positive examination for NSF and their death rates were followed for two years following the exam. The researchers chose a noninvasive skin examination in order to maximize participation and minimize the complications sometimes seen when these patients undergo surgical procedures such as biopsies. In addition, using electronic medical records, patients who had undergone scans with gadolinium-containing contrast agents were also identified and their records were examined to confirm when the exposure took place.

The results showed that of 186 patients, 25 had skin changes consistent with NSF. A total of 25 patients (24 percent) died within two years of the skin examination; those with NSF had a mortality rate of 48 percent compared with 20 percent for those who did not have skin changes consistent with NSF. Patients who had been exposed to gadolinium were almost 15 times as likely to develop NSF skin changes: among the 90 patients with electronic records, 54 had been exposed to gadolinium and 30 percent of these developed NSF compared to only 1 percent of the 36 patients who had not been exposed to gadolinium. Conversely, 94 percent of the 17 patients who developed NSF changes had previously been exposed to gadolinium, compared with 52 percent who did not develop skin changes.

This is the first study to establish the prevalence of NSF-related skin changes in patients undergoing dialysis and the first to quantify the association between NSF skin changes and exposure to gadolinium. Because NSF is a newly reported condition, skin biopsies were available for only five patients and in each of these cases the diagnosis of NSF was confirmed. "The paucity of available skin biopsy specimens highlights that NSF is likely under recognized by many practicing physicians," the researchers state. They also note that the increased risk of death in patients with NSF skin changes largely occurred within the first six months following their examation, suggesting an increased risk of early mortality.

Although additional studies are needed to determine why patients with kidney disease risk developing NSF after exposure to gadolinium, the researchers conclude that contrast agents containing this element should be used only with extreme caution in patients with chronic kidney disease and that, if they are exposed to gadolinium, these patients should subsequently receive regular careful skin examinations. They conclude: "The identification of larger numbers of patients with NSF will allow further investigations into the pathogenesis, treatment, and prevention of this recently described debilitating, and potentially fatal, condition."

In an accompanying editorial in the same issue, Shawn E. Cowper, Phillip H. Kuo and Richard Bucala of Yale University School of Medicine in New Haven, CT, point out that reported cases of NSF have led to a Public Health Advisory urging caution in the use of MRI scans for patients with kidney disease and prompt dialysis in those who have undergone scans involving gadolinium. They note that the study by Todd and colleagues contributes to this evolving story, and that the evidence of early skin changes seen in the study raises the possibility that such changes are more common than was previously thought and may point to an early or less severe form of NSF. Many questions remain about the origins of NSF (including why some patients exposed to gadolinium develop the disease and others do not) and they suggest that studying how cells respond to gadolinium exposure will shed light on this disease. They conclude: "Such information also could facilitate the development of MR contrast agents that have a less toxic response profile, and preserve the high clinical utility of contrast-enhanced MR as an imaging modality in patients with renal insufficiency."
-end-
Articles:

"Cutaneous Changes of Nephrogenic Systemic Fibrosis: Predictor of Early Mortality and Association With Gadolinium Exposure," Derrick J. Todd, Anna Kagan, Lori B. Chibnik, Jonathan Kay, Arthritis & Rheumatism, October 2007; (10.1002/art.22925).

"Nephrogenic Systemic Fibrosis and Gadolinium Exposure: Association and Lessons for Idiopathic Fibrosing Disorders," Shawn E. Cowper, Phillip H. Kuo, Richard Bucala, Arthritis & Rheumatism, October 2007; (10.1002/art.22926).

Wiley

Related Kidney Disease Articles from Brightsurf:

Waistline matters in kidney disease
Does fat matter in kidney disease? The investigators found that all measures of higher abdominal fat content (including visceral fat, liver fat, or subcutaneous fat) and slower walk times were associated with increased levels of cardiometabolic risk factors in adults with non-dialysis dependent kidney disease.

Reducing urinary protein for patients with rare kidney disease slows kidney decline
New findings show that reducing the amount of protein in the urine of patients with focal segmental glomerulosclerosis can significantly slow declines in kidney function and extend time before patients' kidneys fail.

Antioxidant agent may prevent chronic kidney disease and Parkinson's disease
Researchers from Osaka University developed a novel dietary silicon-based antioxidant agent with renoprotective and neuroprotective effects.

Acute kidney injury and end stage kidney disease in severe COVID-19
Many COVID-19 patients experience hematuria, proteinuria and elevated serum creatinine concentration early in the course of the disease.

Genes tell a story about diabetic kidney disease
Studying Finnish genes leads to unique revelations about the development of a serious complication of diabetes, and informs an ongoing genomic study of a Singaporean cohort as part of Singapore's Diabetes Study in Nephropathy and other Microvascular Complications (DYNAMO).

New study provides insight into chronic kidney disease
Researchers have further analyzed a known signaling pathway they believe brings them one step closer to understanding the complex physiology of patients with chronic kidney disease (CKD), which might provide a path to new treatment options.

Predicting risk of chronic kidney disease
Data from about 5 million people (with and without diabetes) in 28 countries were used to develop equations to help identify people at increased five-year risk of chronic kidney disease, defined as reduced estimated glomerular filtration rate (eGFR).

A healthy diet may help prevent kidney disease
In an analysis of published studies, a healthy dietary pattern was associated with a 30% lower incidence of chronic kidney disease.

Is kidney failure a man's disease?
A new analysis of the ERA-EDTA Registry [1] reveals a striking gender difference in the incidence and prevalence of end-stage renal disease.

Chronic kidney disease: Everyone's concern
850 million people worldwide are affected by kidney disease. This worrying figure was published last June.

Read More: Kidney Disease News and Kidney Disease 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.