Intra Hemodialytic Oral Protein and Exercise (IHOPE)
Condition: Kidney Diseases
MeSH terms: Kidney Diseases
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Control; Protein; Protein + Exercise
Intervention type(s): Dietary Supplement; Dietary Supplement; Behavioral
Intervention description(s): A placebo non-nutritive beverage will be administered before dialysis sessions 3 times per week.; A whey protein beverage will be administered before dialysis sessions 3 times per week.; A whey protein beverage will be administered before dialysis sessions 3 times per week. Patients will also exercise by stationary bicycle during dialysis sessions 3 times per week.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Supportive Care