Clinical Measure of Frailty Predicts Risk of Delayed Graft Function

A 10-minute bedside test of frailty can predict the likelihood of delayed graft function (DGF) in patients undergoing kidney transplants, according to a new study in the Archives of Surgery. Frailty has emerged as an important characteristic of health state in the elderly, but in this study, the effect of frailty on DGF was independent of age.

“It’s actually quite difficult to predict who is at higher risk for delayed graft function based on recipient characteristics,” said senior author Dorry Segev, MD, PhD, associate professor of surgery at Johns Hopkins School of Medicine in Baltimore. While hyperacute rejection is largely due to known factors such as blood type—“showstoppers,” in Segev’s words—and long-term organ failure is controlled in large part by how well donor and recipient tissues match, the factors controlling DGF have been harder to tease apart.

Even the underlying cause of DGF is unknown, he said. “That’s the million dollar question.” The suspicion is that inflammation in the patient causes inflammation in the kidney, resulting in ischemia reperfusion injury. “The thinking is that there is something about the milieu that you’re putting that kidney into, some inflammatory state in the recipient, that is causing it.”

“Frailty is well documented as an inflammatory state,” he went on, leading to the hypothesis that frailty might influence DGF. “It makes sense biologically.”

To test that hypothesis, Segev and colleagues prospectively enrolled 183 kidney transplant recipients, all of whom had been cleared by a surgical team for transplantation, and measured their level of frailty immediately before surgery, using a five-part scale:
  • shrinking, assessed by asking the patient if they had unintentionally lost more than 10 pounds in the past year.

  • exhaustion, assessed by two questions about motivation and effort.

  • low physical activity, determined by asking about frequency and duration of leisure activities.

  • time required to walk 15 feet, adjusted for sex and height.

  • grip strength, measured by handheld dynamometry, and adjusted for body mass index.

“The test is entirely objective and takes about five to 10 minutes to administer,” Segev said. The scale has been well validated in the elderly, and is starting to be validated in surgical and kidney disease populations.

In Segev’s study, patients had a mean age of 53 years, and had been on dialysis for a median of 2.5 years. He found that DGF occurred in 15 percent of nonfrail patients, but 30 percent of frail patients. The approximately twofold greater risk for DGF remained after adjusting for multiple variables, including patient age, diabetes, and obesity. “Frailty was the strongest predictor of delayed graft function of any factor having to do with the recipient.”

The measure of frailty has a number of potential uses, according to Segev. “One question is who is a good candidate for a kidney transplant. We have a fairly poor ability to predict which patients are going to do well and which are going to do poorly,” particularly in older adults. “And this is important because kidney transplant is not the only therapy for these patients,” since dialysis remains an option.

“The second question is how to optimize someone’s transplant care,” including organ characteristics. “In a frail patient, I might think twice about putting in a kidney that’s been out of the body for 30 hours, while in a non-frail patient I might be more willing to do that, because I know the risk for developing delayed graft function is half that of the frail patient.” Decisions about length of hospital stay and medications may also be reviewed based on frailty.

If a patient is frail, can presurgical treatment improve their frail state? “That’s the other million-dollar question in this area,” Segev said. Work in this field, called “prehabilitation,” is just starting to emerge. “It would appear intuitive that such rehabilitation would do something useful, but there are no studies completed to know whether that’s true or not.”

Doubts remain

“There is a lot of interest in characterizing the underlying health status of patients before they undergo kidney transplants,” commented Peter Reese, MD, assistant professor of medicine and biostatistics in the Renal Electrolyte and Hypertension Division at the University of Pennsylvania in Philadelphia.

“There are some patients who are worse off than their ages or comorbidities would lead you to believe, and frailty is potentially a powerful syndrome that could be used to predict which patients are going to do well after kidney transplant.”

“But whether or not it would be helpful clinically is unclear,” he said, “partially because it’s not easy to measure.” Most clinicians, he noted, don’t routinely perform handheld dynamometry or walking speed, and the measure of weight loss requires longitudinal data that may not be available. “This would significantly add to the burden of preoperative preparation for kidney transplant patients. Something like frailty may be very important. I’m just not sure frailty itself will ultimately be the one we need to measure. We need to compare it to other things,” in order to find the one that best combines clinical ease with predictive value, Reese said.

Nonetheless, he said, “some kind of summary measure of the patient’s physiologic reserve could be very important, and could add a lot of value” to presurgical planning. “For some patients we might recommend they undergo physical therapy prior to transplant.” For others, who don’t look like good risks on paper or to the eye, but who are not frail or who have good physical status, “maybe we would accept them, whereas previously we might have turned them down.” Whatever the measure of physical reserve that the field chooses, “we are hoping that such measures would allow us to look under the hood.”