In Taiwan, there are more than 90 thousand patients with end-stage renal disease (ESRD)
receiving hemodialysis (HD) island-wide. The leading two causes of death are cardiovascular
diseases and sepsis. Though evidence is clear that exercise training in this population is
beneficial to fitness、quality of life、morbidity, it is seriously underuse. Poor physical
fitness is known to associate with high-leveled systemic inflammation and immune
dysregulation but the detailed relationship remains unclear in the ESRD population. Moreover,
though exercise improves low physical fitness, available research concerning its effect on
the pro-/anti-inflammatory immune response is scarce. In the current proposal, physical
fitness is classified into cardiopulmonary fitness and muscle fitness. Muscle fitness is
further divided into three domains: strength, mass, and oxidative capacity. The 3-year
proposal plan to recruit 90 patients with ESRD who receive regular HD for more than 6 months.
Every participant will go through 3 phases：control phase、training phase and the maintenance
phase (within-subject design). In the control phase, no exercise education or training will
be given to the participants. In the training phase, the participants will receive
in-hospital supervised exercise training prior to HD. The training program will last 6 months
and about 60 training sessions in total. The training protocol contains cyclic aerobic
training in moderate-intensity and high-intensity interval training plus isokinetic
resistance training. In the following maintenance phase, home-based exercise training will be
educated. The control and maintenance phases are 1-2 and 3 months respectively in duration.
Before and after each phase and in the middle of the training phase (5-time points totally),
every participant will receive a thorough evaluation as follows: CPET with noninvasive
cardiac output monitor, isokinetic strength testing, handgrip strength, muscle oxidative
capacity, body composition by dual-energy x-ray absorptiometry, Chinese Kidney Disease and
Quality of Life questionnaire and international physical activity questionnaire and blood
sampling for pro-/anti-inflammatory markers, including chemokine, cytokine, immune cells, and
immuno-regulatory microRNAs, etc. The hypothesis of the proposal is as follows. (I) When
cardiopulmonary fitness/muscle fitness drops to a certain level, the inflammatory immune
response will rise. The proposal aims to find the best biomarkers and their cut-off points
among the various indicators of cardiopulmonary and muscle fitness that reflect immune
dysregulation. (II) Other than physical fitness, cyclic aerobic and resistance training
improves pro-/anti-inflammatory immune dysregulation. Additionally, three months after
cessation of training, a thorough assessment will be performed to examine whether a healthy
lifestyle behavior modification has been achieved and whether the beneficial effect of
physical fitness and immune regulation induced by the training program is maintained. The
goal of each year is as follows. FIRST year: To explore the relationship between
cardiopulmonary fitness and pro-/anti-inflammatory immune response in ESRD patients under HD;
SECOND year: To explore the relationship between muscle fitness and pro-/anti-inflammatory
immune response; THIRD year: To evaluate the effects of cyclic aerobic and resistance
training on physical fitness and pro-/anti-inflammatory immunomodulation in ESRD patients
under HD.