As a dialysis patient and peer coach, Caroline Wilkie knows how postdialysis fatigue and cramping can get in the way of socializing, work, or other responsibilities.
“A lot of us don’t plan things in advance because we never know how tired we’re going to be,” Wilkie said.
Her views and those of other patients with ESRD took center stage recently in a project led by ASN’s Kidney Health Initiative (KHI), a public–private partnership between ASN and the U.S. Food and Drug Administration (FDA), aimed at understanding which symptoms patients find most troubling. The project found that insomnia, fatigue, and cramping were the top-ranked physical symptoms, according to results published in the Clinical Journal of the American Society of Nephrology (CJASN). The top-ranked mood symptoms were anxiety, depression, and frustration.
The ultimate goal of the project is to spur the development of therapies that help address these symptoms and improve patients’ quality of life, said Jennifer E. Flythe, MD, MPH, assistant professor of medicine at the University of North Carolina at Chapel Hill and co-chair of the project. She noted that currently there are no FDA-approved treatments specifically for treating ESRD-related symptoms. This often leaves patients experimenting with non–evidence-based ways to manage symptoms. For example, Wilkie noted, some try pickle juice or mustard for cramps.
“A lot of people just try a lot of different things until they find relief, or some people don’t ever find relief,” Wilkie said.
Prioritizing symptoms
Previous research had documented symptoms that affect ESRD patients, but the KHI project is the first to document how patients rank them, said Steven Weisbord, MD, MSC, associate professor of medicine in the Renal-Electrolyte Division at the University of Pittsburgh School of Medicine.
The KHI study included 32 participants in focus groups in North Carolina, Arizona, and Washington state, along with 87 patients who responded to an online survey. The high frequency of fatigue (94%), cramping (79%), and body aches (76%), along with depression (66%), worry (64%), and frustration (63%), confirmed the results of previous studies by Weisbord and colleagues that used a tool to assess symptoms.
The highest-priority symptoms were consistent across the focus and survey groups in the KHI study. Patients rated symptoms with the greatest impact on day-to-day activities, quality of life, and their family’s finances as the most burdensome. For example, one focus group participant reported in the study, “Sometimes I think I am a burden to my family because I cannot work [because of my symptoms]…Sometimes I get real depressed.”
“What was concerning to them was how frequently these symptoms occurred, the duration, and how unpredictable they were,” said Wendy St. Peter, PharmD, a professor in the College of Pharmacy at the University of Minnesota and the KHI board liaison to the ESRD symptom project. “Those are things that oftentimes as healthcare providers we don’t think about.”
Patients also gave their views about the types of symptom-targeted therapies they might find helpful. Participants reported that their physical symptoms were often interrelated with their mood symptoms. For example, Flythe noted that postdialysis-related fatigue might leave patients so tired they can’t play with their grandchildren or work, which might contribute to a depressed mood. By treating fatigue, physicians might be able to address both problems without having to use pharmacotherapy to treat the mood symptoms, Flythe said.
Additionally, study participants expressed a desire for behavioral therapies that might address their symptoms, such as peer support groups or cognitive behavioral therapy. Given that the average dialysis patient is already taking 19 pills a day and is aware that medications may come with side effects, it is not surprising that patients weren’t eager to add to their pill burden, St. Peter said.
“It was a really good reminder that they are interested in other therapies,” Flythe said.
Symptom strategies
The hope is that these insights into patients’ preferences will drive the development of new symptom-directed therapies or the repurposing of existing medications to ease symptoms in patients with ESRD.
Numerous medications are available to treat insomnia, but there hasn’t been much study about whether they are effective for patients with ESRD, noted St. Peter. A few small studies have looked at the effects of antidepressant medications in patients with ESRD, but some results have been disappointing.
“We just don’t know what’s going to be most effective or whether the medications will be effective at all in dialysis patients,” St. Peter said. She noted it is particularly important to assess whether drugs that are eliminated through the kidneys will be safe in ESRD patients, whose kidneys are compromised.
There was also discussion about behavioral or other therapies that might be helpful. For example, Wilkie suggested that cognitive behavioral therapy or exercise might ease some symptoms. So far, there are limited data on cognitive behavioral therapies in ESRD patients, noted Flythe. A few small studies have looked at the potential benefits of exercise for patients receiving dialysis. She noted the key challenge is finding interventions that are accessible and easy for patients to stick with.
“It’s figuring out what types of exercise programs are sustainable,” Flythe said. “It’s less of a question of whether they can be helpful.”
Another approach to reducing symptoms like cramping and fatigue might be to adjust dialysis itself, noted St. Peter. She explained that rapid removal of fluids and shifts in electrolyte levels during traditional in-center dialysis, which is usually delivered three times a week for 4 hours, might contribute to cramps or fatigue. Slowing the process or using more frequent home dialysis might help, but more study is needed.
“Patients who are getting daily dialysis or longer dialysis oftentimes feel better overall,” St. Peter said. “These therapies haven’t been investigated yet for symptoms such as cramping or fatigue, so those are really important considerations.”
To help drive such research and the development of new therapies, KHI held a workshop with patients, clinicians, industry representatives, and the FDA in January 2018 to develop plans for each of the top-rated symptoms. Those plans will be published later this year. Weisbord cautioned that the process of translating the findings of the KHI project into practice will be challenging and may take a long time.
In the meantime, Flythe hopes the KHI project will help raise awareness among physicians about the importance of symptoms to patients’ quality of life. A study by Weisbord and colleagues found that physicians often weren’t aware of their patients’ symptoms. Weisbord attributed this in part to a focus by nephrologists on adjusting medications or dialysis prescriptions, along with potential discomfort or unfamiliarity with treating conditions like pain or depression.
“When you have a limited time to talk to a patient, oftentimes conversations get focused on numbers,” Flythe said.
But it is important for physicians to ask, Flythe and Weisbord said.
“We need to be very cognizant of patients’ symptoms and what is very important to each patient,” St. Peter said. “They want to feel their care providers are listening to them, that if they’re having symptoms they are taken seriously.”
Wilkie also urged patients to speak up and share their symptoms with their physicians.
“It helps, even if there’s nothing that can be done; it helps for your doctors to know what you’re going through,” Wilkie said.
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