Study Reveals Deadly Effects of Inactivity for Kidney Transplant Recipients

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A new study indicates that not getting enough exercise can be fatal for kidney transplant patients.

“From our research we can conclude that a low level of physical activity is a new—and modifiable—risk factor for cardiovascular and all cause mortality in these patients,” said Dorien Zelle, of the University Medical Center Groningen, in the Netherlands, lead author of the Clinical Journal of the American Society of Nephrology (CJASN) study.

Intervention trials are needed to investigate whether increasing physical activity levels may improve outcomes after transplantation, she added.

The price of inactivity

Patients with advanced chronic kidney disease, particularly

A new study indicates that not getting enough exercise can be fatal for kidney transplant patients.

“From our research we can conclude that a low level of physical activity is a new—and modifiable—risk factor for cardiovascular and all cause mortality in these patients,” said Dorien Zelle, of the University Medical Center Groningen, in the Netherlands, lead author of the Clinical Journal of the American Society of Nephrology (CJASN) study.

Intervention trials are needed to investigate whether increasing physical activity levels may improve outcomes after transplantation, she added.

The price of inactivity

Patients with advanced chronic kidney disease, particularly those receiving dialysis, tend to get little exercise. Most increase their physical activity after receiving a kidney transplant, but only slightly. Studies in the general population have shown that low levels of physical activity increase individuals’ risk for cardiovascular disease and premature death. Zelle and her colleagues looked to see whether the same holds true for kidney transplant recipients.

Maintaining heart health is particularly important for these patients, given that kidney transplant recipients have a fourfold to sixfold increased risk of dying of heart-related causes than do individuals in the general population.

“Partly this is due to clustering of several risk factors. High cholesterol, high blood pressure, and obesity are often seen after transplantation and create a ‘bad’ risk profile,” said Zelle.

To study whether low exercise levels are linked to cardiovascular disease and premature death in kidney transplant recipients, Zelle and her team studied the health of 540 kidney transplant recipients between 2001 and 2003, assessing physical activity through questionnaires and recording deaths until August 2007. With regard to the guidelines for minimum requirements of physical activity, 260 (48 percent) of patients were not meeting the criteria, and 79 (14.6 percent) were completely inactive.

During the study period, 81 patients died, 37 of whom succumbed to cardiovascular ailments. Those with lower levels of physical activity experienced higher rates of death. Cardiovascular deaths occurred in 11.7 percent of patients considered inactive, 7.2 percent of those considered moderately active, and 1.7 percent of those who were active. Deaths resulting from any cause occurred at rates of 24.4 percent, 15.0 percent, and 5.6 percent in these respective groups.

Kidney specialists not involved with the research said that the findings provide valuable information for physicians and patients.

“There seems to be relatively little attention devoted to self-care among kidney transplant recipients besides issues of medication adherence, and there does not seem to be enough scientific research on patient-related modifiable factors influencing graft or patient survival,” said Elisa Gordon, PhD, MPH, of the Northwestern University Transplant Outcomes Research Collaborative in Chicago. “Thus, this paper makes a very nice contribution toward clearly showing the significant association of the patient-related factor of physical activity with patient survival.”

Gordon also noted that the study suggests a direct effect of exercise on kidney health.

“The authors found that physical activity levels are related to creatinine clearance. In my own research, I similarly found that physical activity levels are related to estimated glomerular filtration rates, suggesting that graft function is affected by physical activity,” she said. (Gordon EJ et al., Transpl Int 2009; 22:990–998).

Jamie MacDonald, PhD, of Bangor University’s School of Sport, Health and Exercise Sciences and the Renal Unit at Gwynedd Hospital in the United Kingdom, added that the study’s finding of a linear dose–response effect between physical activity and risk reduction is of particular note.

“Previous studies in patients with chronic kidney disease have shown reverse epidemiology between certain risk factors and outcome—such as body mass index—or a ceiling effect with the highest levels of physical activity not necessarily inferring greater benefit for survival,” MacDonald said.

Interventions needed

Zelle noted that there may be several reasons why kidney transplant recipients have low levels of physical activity. Exercise capacity is approximately 30 percent lower in these patients than in control individuals, and patients often have low muscle mass before transplantation as a consequence of their chronic kidney disease and dialysis treatments.

“A lack of physical activity after transplantation can adversely affect muscle mass; so it’s obvious that to restore and maintain muscle mass after transplantation, regular physical activity is required,” said Zelle.

Zelle noted that it has become a habit for kidney transplant recipients to be inactive. “Before transplantation most patients had very low levels of physical activity mainly because of the burden of being a dialysis patient,” she said.

Although this study did not assess the causes of low physical activity levels in kidney transplant recipients, Gordon’s work has indicated that patients’ psychosocial factors are involved and that patients reported that transplant professionals inconsistently communicated to them about engaging in physical activity (Gordon EJ et al., Clin Transplant 2010; 24:E69–81; Gordon EJ et al., Chronic Illn 2009; 5:75–91).

Zelle and her coauthors, in collaboration with researchers at the University Medical Center Maastricht, plan to design a randomized controlled lifestyle intervention study to determine whether increased physical activity can improve the health and prolong the lives of transplant recipients. Patients will take part in a supervised exercise program and receive individual counseling to promote exercise and a healthy diet.

“It is often hard to change habits, and we hope that our intervention program will provide help in this,” said Zelle.

MacDonald offered some recommendations for other types of studies that should be conducted. “Researchers should consider further epidemiological studies, perhaps using time-lagged analyses to provide stronger evidence of cause and effect. Funding bodies can also have greater confidence to support experimental exercise intervention studies,” he said. “These types of studies will not only strengthen the evidence base for physical activity, but by elucidating mechanisms may also identify further targets for intervention. For example, does a lack of physical activity cause low muscle mass or the other way around?”

Gordon suggested some immediate steps that can be taken. “In my opinion, these findings underscore the need for transplant health care providers and nephrologists to routinely recommend engaging in physical activity and specify required amounts and types of exercise, emphasize the importance of engaging in physical activity, and address any barriers that patients may have such as limited self-efficacy. Also, transplant or health care centers should promote a chronic care model approach to support kidney transplant recipients such as through the provision of rehabilitation centers.”

Study coauthors include Eva Corpeleijn, PhD, Ronald Stolk, MD, Mathieu de Greef, PhD, Reinold Gans, MD, Gerjan Navis, MD, and Stephan Bakker, MD, PhD (University Medical Center Groningen, the Netherlands).

Disclosures: This research was performed within the framework of the Centre for Translational Molecular Medicine, project PREDICCt (Prediction and Early Diagnosis of Diabetes and Diabetes-related Cardiovascular Complications, grant 01C-104), and supported by the Netherlands Heart Foundation, Dutch Diabetes Research Foundation, and Dutch Kidney Foundation.

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