Optimizing Cardiovascular Health and Physical Function in Hemodialysis Patients Through Volume Control and Exercise

Patients with kidney failure require regular hemodialysis (HD) therapy 3-4 days per week to
filter their blood and remove excess fluid. However, the dialysis process is inefficient, as
it typically does not remove all of the fluid and waste products that accumulate in patients
since their last treatment. This accumulation of excess fluid is called volume overload (VO).
Chronic VO can have adverse effects on the heart and arteries, primarily by increasing blood
pressure, eventually lead to enlargement of the heart and cardiac dysfunction (1-3). Some
evidence also suggests that it adversely impacts patient's physical activity levels and
function.

Past research has shown that a patient's fluid volume can be controlled using 'volume
control' strategies. These strategies involve progressively reducing a patient's
post-dialysis body weight by slowly increasing the amount of fluid removed during each
dialysis session (e.g., by removing an extra 200-300ml of fluid each session). Patient's
dietary sodium intake is simultaneously restricted to control their thirst and to prevent
fluid intake and accumulation between their treatments. Stringent volume control has been
shown to improve cardiovascular health and reduce mortality (2-3), but is rarely/never
practiced in U.S. dialysis clinics. Instead, patients in the U.S. are normally provided blood
pressure or other medications to help mitigate the effects of excessive fluid accumulation
between sessions. However, there is little evidence that these medications are efficacious,
as most have no impact on fluid accumulation per se. Moreover, dietary sodium restriction, a
principle component of successful volume reduction strategies, often requires comprehensive
changes to an individual's diet due to the pervasive inclusion of salt in the U.S. food
supply. Registered dietitians provide the majority of nutrition counseling to HD patients,
but they lack the time to provide the level of care needed to sustain patient's dietary
changes. As a result, chronic volume overload is a common problem in U.S. dialysis patients,
as there are no established protocols for managing this problem other than through
pharmacological interventions with no proven efficacy.

The investigators are proposing a multifactorial intervention designed to improve HD
patient's cardiovascular health and physical function. The intervention includes a novel
volume control protocol that may be combined with exercise training to optimize the benefits
of the volume control strategy. HD patients from selected clinics will be randomly assigned
to: 1) volume control protocol (VC); or 2) VC + exercise training (VCE). The VC protocol will
include 2 primary components: 1) a progressive increase in the amount of fluid removed during
a patient's dialysis treatment (ultrafiltration volume) at the discretion of the patient's
physician, and 2) a dietary intervention to improve patient's food choices, focused on
reducing the intake of fast and processed foods that are high in sodium, as well as
phosphorus additives that may also have damaging effects on the heart, arteries, and bone.
The dietary intervention will involve training the existing clinic staff to help deliver
better and more consistent nutritional messages to their patients, to supplement the work of
the existing clinic dietitian.

Patients randomized to exercise group (VCE) will receive the VC intervention in addition to a
personalized exercise training and physical activity prescription from a "lifestyle
interventionist" (LI). This will include exercise during dialysis treatment, as well as
counseling on how to increase physical activity levels outside of the clinic - namely at home
or in the community.

The LI will also help deliver the nutritional education component of the VC protocol. As most
HD clinics typically employ one or more full time registered dietitians, the LI will work
closely with them to support their work. The LI will focus on basic nutrition messages
including decreasing the intake of fast and processed foods, ensuring regular meals, and
adequate protein intake. This education will be conducted according to the Fresenius Tech
Talk model. Short in-services will be held with clinic staff to educate them on general
nutrition principles. Staff will be encouraged to incorporate these talking points into
patient conversations. Outcomes will be evaluated by the LI at baseline, and after 6 and 12
months. Primary outcomes include mean arterial blood pressure and physical function.
Secondary outcomes include: hospitalization rates, cardiovascular function, dialysis
compliance, fall incidence, and blood pressure medication prescription.

This study will provide novel information regarding the effects of a novel volume control
strategy and exercise training on physical function and cardiovascular health in HD patients.
Results from this study will enable nephrologists to make more informed decisions regarding
the extent to which this low-cost treatment strategy should be included as a component of the
standard care in their clinics. Ultimately, this could lead to greater use of this treatment
strategy and result in significant improvements in the health and quality of life of this
critically ill patient population.

Inclusion Criteria:

- Any patient with a blood pressure > 130/85, or prescribed at least one
anti-hypertensive medication

Exclusion Criteria:

- Patients already below their prescribed dry weights and who are normotensive in the
absence of hypertensive medications, and without peripheral edema