The right mix of ingredients
The MU Kidney Transplant Research Team consists of Richard Madsen, emeritus statistics professor; Cindy Russell, assistant professor of nursing; Gilbert Ross, MU Transplant Program interim director; Catherine Ashbaugh, advanced practice nurse, MU Health Care-Transplant Department.
A 64-year-old man who recently returned home after undergoing a kidney transplant reaches for his prescription. He removes the cap from his pill bottle and shakes an anti-rejection drug into his hand. Washing it down with a swig of orange juice, he replaces the cap and puts the bottle back on his kitchen windowsill. And even though she’s not there, Cindy Russell knows exactly when this daily ritual occurred — and she knows when it slipped the patient’s mind.
An assistant professor at the school, Russell is using a high-tech device to track the medication-taking habits of more than 200 renal transplant recipients. Each patient in her study, which is funded by a $220,500 grant from the National Institutes of Health, takes anti-rejection medicine from bottles topped with a special cap that contains a computer chip. The chip records each time the cap is removed from the bottle, and Russell downloads the information to her computer, creating a database that may yield valuable information about the postoperative medication compliance patterns of transplant recipients.
Organ transplants offered a second chance at life for almost 16,000 people last year, according to the United Network of Organ Sharing. Yet if organ recipients don’t follow a demanding regimen of anti-rejection drug therapy following their operations, they face alarming consequences that can cost the very life the transplant saved.
Without careful and diligent medication management, a transplant patient’s body will treat the new organ as a foreign substance and attack it, destroying the organ and potentially killing the patient. For kidney transplant patients, organ rejection, which can be immediate or occur over time, may cause the patient to lose all kidney function and result in the need for uncomfortable and expensive dialysis. Yet with the average transplant patient taking 17 pills per day, usually for a variety of conditions such as diabetes and hypertension, getting all the doses correct can be a complex and confusing task.
“Most people wait a long time to get a transplant, and there’s a shortage of organs available,” says Russell. “It’s a shame to use precious organs on people who don’t or can’t take their medications properly in order to keep their new kidney.”
Russell hopes that her study will uncover patterns or commonalities among patients who fail to take their drugs properly, offering insights that may lead to useful interventions.
Russell’s methodology involves the most accurate remote method of medication monitoring available. Only two previous studies with renal transplant recipients have used the 5 TrackCap from Aardex Ltd., a Swiss company that calls itself “the world leader in electronic devices and software for monitoring prescription drug intake by ambulatory patients.” The $110-per-cap cost has made the 5 TrackCap more popular for research purposes than for clinical use.
“This isn't’t an intervention, it’s simply a measurement tool,” Russell notes. “It allows people to work with a health care team to see how well they do with medication management over time.” Although Russell’s research program deals exclusively with renal transplant patients, she says that the cap could be a useful tool for high-risk residents in assisted living facilities.
Historical research on medicine-taking habits varies widely, yet previous studies indicate that about 25 percent of renal transplant patients do not take their prescriptions properly. Russell’s work is unique in its search for behavioral patterns related to taking medication. In fact, when presenting data on the first 44 patients in the study, Russell identified several distinct patterns.
“No one takes their meds early,” she says. “Some, about 30 percent, take their medicine consistently on time. Overall, the group missed doses about 10 percent of the time.”
Russell’s ultimate aim is to determine how the retention and health of the kidney correlates to anti-rejection medication patterns during a two-year time frame. At the same time, her study will measure variables that may predict specific patterns and allow for the development of useful long-term interventions to improve medication compliance and potentially improve transplant outcomes. To accomplish this, Russell is tracking the habits of her subjects for six months to a year and then reviewing their health after two years.
Patients fail to take their medicines correctly — even when those medicines may mean the difference between life and death — for many reasons. Mental health, social support, and the degree of self-confidence a patient has in his ability to properly manage his medicines all play a role in subsequent behaviors. In addition, prior research has established that patients who take their medications correctly 80 percent of the time are considered compliant. Thus, even “compliant” patients are allowed room for error.
In the particular case of transplant patients, specific issues may impact the ability to take anti-rejection medicines properly.
One such issue is cost, which typically runs around $1,500 per month for antirejection drugs. Skipping doses here and there may be a matter of economic necessity in some cases. This is despite the efforts of the tax-supported Missouri Kidney Program, which acts as a payor of last resort in instances where a patient earns too much to qualify for Medicaid but not enough to afford medicines without other financial help.
The side effects common to the immunosuppressants that prevent the body from rejecting a transplanted organ are another possible cause for noncompliance. For instance, many post-transplant patients take the steroid Prednisone, which can cause weight gain, bone loss and immune suppression leading to a risk of illness or infection. Other common post-transplant drugs may cause gout, diarrhea, gum disease and hair growth. The typically large pills also may be difficult to swallow for some patients.
The process of refilling prescriptions at a pharmacy or by mail may be daunting, especially for older patients who lack helpful friends or family. And the drugs must be taken once or twice daily for as long as the organ lasts — years in many cases.
Despite the difficulties inherent in the medication process, Russell points out that dialysis is much more difficult to tolerate and more expensive in the long run.
“There are better long-term outcomes for transplant patients than for those who do not receive a new kidney,” she says. “Our study was funded in part because the government wants people to keep their transplanted organs, especially since dialysis becomes more expensive than transplant after several years.”
About 12 percent of kidney transplant patients reject their initial organ and receive a second transplant. It is not known how many of those reject the initial organ due to medication noncompliance. However, with need outpacing the demand for healthy kidneys, Russell’s work could be key to reducing the number of second-time transplants as healthcare professionals better understand how to help patients manage their medications.
Russell is using Bandura’s Social Cognitive Theory to guide her assumptions. The theory is a well-known model that allows researchers to understand behavior and behavioral change. Self-confidence is one factor the theory takes into account as an indicator of behavior. Another important variable involves the subject’s own expectations as a force to shape behavior. For example, a subject who strongly desires a future free of dialysis is more likely to do whatever is necessary to achieve that expectation.
The patients in Russell’s study have been recruited from the University’s transplant program and from the University of Tennessee in Memphis.
In addition to the NIH grant, Russell has received funding from the National Kidney Foundation, the American Nurses Foundation/Sigma Theta Tau, MU Research Council and the John A. Hartford-Atlantic Foundation.
Russell’s passion grew from professional experience as an advanced practice nurse working with heart and kidney transplant patients at University Hospital in Columbia.
“One of the problems the transplant team faced was compliance with meds,” she says. “There are so few kidneys available, and we want the people who do get them to do well.” Russell was frustrated by patients who stopped taking their medications or didn't’t take them properly. “I thought it would be a good area to study more,” she adds, “especially because there were no interventions that had been tested through a scholarly, empirical approach in the literature.”
Russell imagines the interventions her work could lead to would involve nurses, pharmacists and social workers, who would provide some type of ongoing phone, online, group or written support to help patients stay on track.
“One of the heartwarming things I found that surprised me, is that people we ask to be in the study are so willing to become involved in order to help other transplant patients and society at large,” Russell says. “They feel they’ve been given a gift and they want to give back. That’s one of the reasons I like research in this field – the people are unique and wonderful.”