Sit Less, Interact, Move More (SLIMM) Intervention for Sedentary Behavior in Chronic Kidney Disease (CKD)

There are an estimated 15.5 million adults with stage 3 chronic kidney disease (CKD) while
only about 600,000 patients have end-stage renal disease (ESRD) in the United States. This is
because most of the people with CKD die before they reach ESRD. In order to decrease the high
mortality in the CKD population, the "non-renal" issues that contribute to increased
morbidity and mortality in this population need to be addressed.

Relevance of sedentary behavior in CKD: Prolonged sitting time (as assessed by a
questionnaire or television viewing time) was associated with lower kidney function. Total
and light physical activities, measured objectively with an accelerometer were found to be
positively associated with kidney function in a study of community dwelling adults. In an
analysis of National Health and Nutrition Examination Survey (NHANES) data, it was noted that
participants with CKD spent more than two-thirds of the awake time in sedentary activities
and longer sedentary duration was associated with increased mortality. It was also noted in
another study that compared to those with CKD, those on maintenance hemodialysis had 3.4 fold
higher odds of being sedentary independent of demographics, co-morbidity, body size, serum
C-Reactive Protein (CRP) and albumin. Thus, sedentary behavior is very common in CKD, appears
to worsen with more advanced kidney failure and increases mortality risk in this population.

Feasibility of replacing sedentary activities with moderate/ vigorous physical activities:
Moderate/ vigorous physical activities are less likely to be an effective replacement for
sedentary activities as most Americans do not reach even the current goals and achieving the
currently recommended levels of 2.5 hrs/ week of moderate/ vigorous activities would account
only for 2% of the total awake time (112 hours/week). Therefore, decreasing sedentary
activities must involve an increase in activities that are less intensive than moderate/
vigorous activities.

The concept of Non- Exercise Activity Thermogenesis (NEAT) and biological relevance of light
intensity activity: In a overfeeding study, it was demonstrated that increase (average 336
kcal/day) in non- exercise activity thermogenesis accounted for 10-fold differences in fat
storage, directly predicted resistance to fat gain and explained most of the variations in
weight gain between participants. Obese persons have less non-exercise activity thermogenesis
and spend an average of 2 hrs/d more in a seated position compared to lean persons.
Objectively measured light activity was inversely associated with insulin resistance and
cardiometabolic risk factors. Daily lifestyle activities were negatively associated with
insulin resistance. Thus, replacing sedentary activities with non-exercise intensity
activities of daily living could increase energy expenditure and decrease adiposity.

Determining what kind of light activity would be most beneficial in replacing sedentary
activity: As standing (~ 1.5 Metabolic Equivalents of Task (METs)) is by definition
non-sedentary (i.e. not sitting or lying down), one might consider replacing sitting duration
with standing duration in order to decrease sedentary behavior. However, replacing sitting
duration with casual walking (2 to 2.9 METs) duration might be even more beneficial. This
notion is supported by the following theoretical calculations of energy expenditure. Assuming
16 hrs/day of awake time, it was calculated that the weekly energy expenditure for a person
weighing 80 kg for trade-off of 1 to 5 min/hr of sedentary activity at 1.2 METs with 1.5 METs
(standing intensity activities) or 2.5 METs (casual walking intensity activities). Additional
kcal/week was calculated as the difference in energy expenditure between sedentary activity
and 1.5 or 2.5 METs activity using the equation Kcal/ week = (METs/hr) x weight in kg X
weekly duration of the physical activity. Trade-off of 1-5 min/hr of sedentary duration with
standing intensity activities duration is expected to result in additional weekly expenditure
of 50-250 Kcal only. On the other hand, similar trade off of sedentary duration with casual
walking intensity activities duration is expected to result in ~ 200 to 1000 Kcal/ week of
additional energy expenditure. This is consistent with prior observation that increase in
non-exercise activities could lead to an additional 350 Kcal/d of energy expenditure in obese
individuals.

Indeed, in the NHANES analyses, it was noted that trade-off sedentary duration for light
intensity (2.0 to 2.9 METs) activities but not for very light intensity (1.5 to 1.9 METs)
duration was associated with significantly lower risk of mortality. Thus, replacing sedentary
duration with casual walking duration could increase energy expenditure and decrease
mortality in CKD.

Inclusion Criteria:

- Stage 3/4 Chronic Kidney Disease, as defined by estimated glomerular filtration rate
(eGFR) 15 to < 60 ml/min/1.73m^2

- Body Mass Index (BMI): 25 to 39.9 kg/m^2

- Able to achieve gait speed of > 1 m/sec and able to walk ≥ 320 meters in the 6-minute
walk test

Exclusion Criteria:

- Previous renal replacement therapy

- Life expectancy < 1 year

- Pregnancy

- Prison incarceration