Chronic kidney disease is a progressive inflammatory disorder affecting approximately 15% of US adults, and the prevalence is increasing rapidly. Advanced chronic kidney disease requiring hemodialysis is associated with multiple co-morbid conditions that greatly reduce physical function and quality of life, including muscle wasting, bone disorders, and cardiovascular disease. Protein-energy malnutrition is especially common for reasons including poor nutrient intake, amino acid losses during dialysis, and elevated intradialytic catabolism; these factors promote loss of lean mass and declines in physical function. Low physical function and adverse changes in body composition accelerate development of other co-morbid conditions, highlighting the cycle of disease and disability characteristic of this population.
Numerous pharmacological therapies are commonly used in an effort to reduce the incidence or severity of chronic kidney disease co-morbidities, but these treatments are associated with high costs and significant side effects. Furthermore, the complexity of chronic kidney disease suggests multiple therapeutic approaches may be beneficial in this population. Intradialytic protein supplementation and exercise training during dialysis are two lifestyle interventions that have been suggested as potential methods to mitigate the cycle of disease and disability. Studies have shown that both parenteral and oral intradialytic supplementation improve protein homeostasis, increase serum albumin and prealbumin levels, and have anabolic effects on skeletal muscle. However, the effect of intradialytic protein on functional disease outcomes in this population is not known. Similarly, numerous studies have demonstrated that intradialytic exercise training has beneficial effects on physical function and quality of life, but surprisingly few studies have examined its effect on other clinical outcomes, particularly cardiovascular disease.
The goal of this research was to examine the relationships between the comorbid conditions associated with advanced chronic kidney disease, and determine the efficacy of intradialytic protein supplementation and exercise training as therapeutic approaches. This goal was accomplished through a series of studies both in animal models and also in clinical populations. In a mouse model of renal insufficiency, a combination of soy protein and exercising improved bone microarchitecture and a main effect of soy protein consumption was observed for improvements plasma urea as an indicator of renal function; results from this study an others prompted consideration of these effects in a clinical population.
In a cross-sectional analysis of sixty hemodialysis patients, we found multiple aspects of chronic kidney disease to be interrelated, supporting the idea of the cycle of disease and disability characteristic of these patients. This study was notable for its comprehensive inclusion of functional outcome variables associated with hemodialysis treatment in an effort to characterize relationships among these factors, and possibly provide information on how best to intervene to improve health outcomes in this extremely sick population. For the first clinical intervention study, seventeen hemodialysis patients completed a four month intradialytic cycling program; exercising during dialysis improved physical functioning and improved cardiovascular disease risk as measured by serum alkaline phosphatase and epicardial fat thickness.
Protein intake during dialysis, either soy or whey protein, attenuated inflammation associated with a single dialysis session and reduced the acute phase protein response after a six month supplementation program. Long-term protein intake also improved physical functioning and reduced circulating alkaline phosphatase levels, similar to the findings after four months of intradialytic cycling. Taken together, these data suggest modest benefits of intradialytic exercise and protein supplementation on functional outcomes in this critically ill population. Future directions include investigating the combined effects of intradialytic protein and exercise in maintenance dialysis patients, as the complexity of the disease suggests multiple therapeutic strategies may be necessary to improve health outcomes and quality of life for this population
