February 27, 2012

Simple ‘frailty’ test predicts kidney transplant outcomes

A simple 10-minute bedside assessment conducted prior to surgery appears to be the best method yet for predicting which kidney transplant patients will do well with their new organs, just-published Johns Hopkins research suggests. A report on the research, which appears in the February issue of the Archives of Surgery, suggests that a recently developed test of frailty, typically used to assess the physiological reserve of elderly patients, is also a useful measure for transplant candidates of all ages.

“Few current measures are accurate in predicting kidney transplant success, but we think we have identified one that works incredibly well,” said study leader Dorry L. Segev, an associate professor of surgery at the Johns Hopkins University School of Medicine. “A few years ago, we showed that a frailty score is a simple yet powerful bedside tool to predict surgical outcomes in elderly patients, and now it seems it can do the same for younger patients with chronic diseases like kidney failure.”

Frailty, Segev says, is medically best defined as a low level of physiological reserve and reduced ability to withstand stress to the body. It is measured using a five-point scale developed at Johns Hopkins. Patients are classified as frail if they meet three or more of the following criteria: shrinking (unintentional weight loss of 10 or more pounds in the previous year), weakness (decreased grip strength as measured by a hand-held dynamometer), exhaustion (measured by responses to questions about effort and motivation), reduced physical activity (determined by asking about leisure time and activities) and slowed walking speed (the time it takes to walk 15 feet).

For the current study, Segev and his team measured frailty in 183 patients prior to kidney transplant between December 2008 and April 2010. Twenty-five percent of the patients met the criteria for frailty, a figure three times higher than in elderly adults who live at home. Kidney transplant patients classified as frail were nearly twice as likely to have early problems with their new organs, a sign that their new kidneys would be more likely to fail in the future. This increased risk of a poor outcome, Segev says, occurred regardless of the age of the transplant recipient.

Segev and his team used the short-term outcome of delayed graft function—meaning a nonfunctioning organ within the first week after transplant—as a marker for risk of longer-term concerns. Although the transplanted kidney may recover and work eventually, he says, it is unlikely to work for as long as a kidney that begins working more quickly in its new body. Researchers found delayed graft function, or DGF, in 30 percent of the patients deemed frail and in just 15 percent of those who were not.

“This information tells us how long the kidney will likely last and how to best treat the patient,” he said. “Our ability to predict delayed function of a new kidney should help overcome one of the biggest barriers to improving outcomes in transplant right now.”

Segev, who is director of clinical research for transplant surgery at Johns Hopkins, says that accurate predictions can help guide clinical decisions, such as ensuring that frail patients receive organs at least risk of DGF. For example, the risk of DGF increases when a kidney spends a longer time outside the body on its way from donor to recipient. Segev says that a kidney coming from across the country might not be the best kidney for a frail patient, since it would be less likely to function quickly and thereby more likely to have problems down the road.

The link between frailty and chronic kidney disease may be found in certain markers typically associated with inflammation, Segev says. As some people age, such genes and proteins may be expressed at higher levels. Frailty, typically found in at least some measure in the elderly, appears to occur in younger kidney patients undergoing dialysis as well. Those who are classified as more frail, young or old, seem to also have a risk of developing inflammation in the new transplanted kidney, which can lead to poor outcomes.

“We have found similarities between what makes people age and what makes dialysis patients sick,” Segev said. “But what makes people frail in the first place and what part of frailty affects the kidneys are the questions we have yet to answer.”

This research was supported by a Clinical Scientist Development Award from the Doris Duke Charitable Foundation.

Other Johns Hopkins researchers involved in the study are Jacqueline M. Garonzik Wang, Priyanka Govindan, Jack W. Grinnan, Minghao Liu, Hassan M. Ali, Anindita Chakraborty, Vaibhav Jain, Reside L. Ros, Nathan T. James, Lauren M. Kucirka, Erin C. Hall, Jonathan C. Berger, Robert A. Montgomery, Niraj M. Desai, Nabil N. Dagher and Jeremy D. Walston.


Related websites

Comprehensive Transplant Center at Johns Hopkins

Dorry Segev