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Chronic kidney disease (CKD) patients receiving hemodialysis treatment (CKD stage 5) suffer
from a variety of co-morbid diseases, many of which may be mechanistically linked. Protein
malnutrition, muscle catabolism and wasting are especially common, and these lead to reduced
muscle strength, declines in physical function, and low levels of physical activity.
Physical inactivity exacerbates these functional declines, and also promotes cardiovascular
disease (CVD) and bone disorders. This cycle of disease and disability greatly reduces
quality of life (QOL) and increases mortality rates in dialysis patients.
Many factors contribute to the development of these co-morbidities. Chronic inflammation is
believed to be a cause and a consequence of the protein malnutrition, CVD and bone disorders
in dialysis patients. In addition, abnormalities in mineral metabolism resulting from the
deficit in kidney function promote the loss of mineral from bone and the deposition of
mineral in the vasculature, a process termed vascular calcification (VC). VC is associated
with a variety of CVD-related disorders, including arterial stiffness, increases in arterial
wall intima-media thickness (IMT), left ventricular hypertrophy (LVH), and declines in
cardiac function. As a result of these abnormalities, cardiovascular events are 10 to 30
times greater in dialysis patients than in age- and sex-matched subjects in the general
population.
A variety of pharmacological therapies are commonly used to help prevent or attenuate the
progression of CKD co-morbidities; however, morbidity and mortality in this population
remain extremely high, indicating that additional therapeutic strategies that may improve
the health and QOL in this population are needed. Recently, the National Kidney Foundation
recommended that dialysis patients increase their protein intake to 1.2 g/kg/day to help
prevent protein malnutrition; however, little is known about the efficacy of this
recommendation. Intradialytic (during dialysis) protein supplementation has been shown to
increase serum albumin levels11, and also increases amino acid uptake into skeletal muscle,
an effect that is potentiated by both resistance and endurance exercise. However, the
individual and combined effects of intradialytic protein supplementation and exercise
training on lean mass, muscle strength, and physical function is unknown. Furthermore,
intradialytic protein supplementation and exercise training improve many risk factors
associated with CVD and renal bone disease (e.g., plasma lipids, inflammatory variables),
but their effect on functional CVD outcomes (e.g., arterial stiffness, VC, IMT, LVH,
myocardial performance) and bone health in dialysis patients is unknown.
The primary objective of the proposed research is to evaluate the efficacy of intradialytic
oral protein supplementation, with and without concomitant intradialytic endurance exercise
training (cycling), on physical function, CVD risk, and bone health. We will also examine
potential mechanisms for these effects, and determine if improvements in these factors lead
to improvements in QOL. Hemodialysis patients will be randomized to the following groups
for 12 months: 1) usual care/control (CON); 2) intradialytic protein supplementation (PRO);
or 3) intradialytic protein supplementation + exercise training (PRO+EX).
Primary Aim #1: Examine the effects of intradialytic oral protein supplementation and
exercise training on physical function.
Hypothesis #1: Physical function, as assessed by a shuttle walk test, will improve in
PRO+EX and PRO, compared to CON, and the magnitude of improvements will be greatest in
PRO+EX. In secondary analyses, we also will examine the effects of our interventions on
other variables related to physical function, including lean body mass, muscle strength, and
activities of daily living (ADL) assessments.
Primary Aim #2: Examine the effects of intradialytic oral protein supplementation and
exercise training on CVD risk.
Hypothesis #2: CVD risk, as assessed by carotid artery stiffness, will improve in PRO+EX
and PRO, compared to CON, and the magnitude of improvements will be greatest in PRO+EX. In
secondary analyses, we also will examine the effects of our interventions on other factors
related to CVD risk, including carotid IMT, myocardial performance, LVH, aortic
calcification, and epicardial fat levels.
Primary Aim #3: Examine the effects of intradialytic oral protein supplementation and
exercise training on bone health as determined by bone mineral density (BMD).
Hypothesis #3: BMD will be reduced significantly more in CON than in PRO+EX or PRO. We
anticipate that BMD will remain stable in PRO+EX or PRO. Because the exercise is not bone
loading (i.e., invoking ground or joint reaction forces), we do not expect additive effects
of PRO+EX on BMD.
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