Invest Clin 65(3): 346 - 357, 2024 https://doi.org/10.54817/IC.v65n3a07
Corresponding author: Changdong Zhu. Department of Clinical Laboratory, Lujiang County People’s Hospital,
Hefei, China. E-mail: zhucd2023@163.com
The effect of regular exercise combined with
quantitative nutritional support on immune
function indicators such as CD3+, CD4+,
CD8+, and nutritional status in dialysis
patients.
Chunfeng Kong
1
and Changdong Zhu
2
1
Department of Hemodialysis, Lujiang County People’s Hospital, Hefei, China.
2
Department of Clinical Laboratory, Lujiang County People’s Hospital, Hefei, China.
Keywords: hemodialysis; immune function; nutritional status.
Abstract. To study the effect of regular exercise and quantitative nutri-
tional support on dialysis patients’ immune function indicators and nutritional
status, 100 uremic patients who underwent hemodialysis treatment in our hos-
pital from February 2021 to February 2023 were selected as the study subjects.
They were divided into a control group (n=50) that received regular exercise
and routine nutritional support, and a research group (n=50) that received
regular exercise and quantitative nutritional support. This study compared the
baseline levels of nutritional indicators such as prealbumin (PA), transferrin
(TF), serum albumin (SAB), and hemoglobin (HB); cellular immune indicators
such as CD3+, CD4+, and CD8+; as well as humoral immune indicators such
as immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin
M (IgM) at enrollment and after three months of intervention. At the time of
enrollment, there were no significant differences in nutritional indicators be-
tween the two groups of patients (
p>0.05), nor in the levels of cellular immune
indicators (
p>0.05) or humoral immune indicators (p>0.05). After three
months of intervention, nutritional indicators such as PA in all patients in the
experiment grew (
p<0.05), and those in the research group exceeded the con-
trol group (
p<0.05). Similarly, the levels of CD3+ and other cellular immune
indicators and the concentrations of IgA and other humoral immune indicators
increased in both groups after three months of intervention (
p<0.05). Howev-
er, these increases were higher in the research group than in the control group
(
p<0.05). Regular exercise combined with quantitative nutritional support can
effectively improve hemodialysis patients’ nutritional index levels, nutritional
status, immune index levels, and immune function.
Effect of regular exercise and quantitative nutritional support on dialysis patients 347
Vol. 65(3): 346 - 357, 2024
Efecto del ejercicio regular, combinado con soporte nutricional
cuantitativo, sobre indicadores de la función inmune tales
como CD3+, CD4+, CD8+, y el estado nutricional en pacientes
en diálisis.
Invest Clin 2024; 65 (3): 346 – 357
Palabras clave: hemodiálisis; función inmune; estado nutricional.
Resumen. Para estudiar el efecto del ejercicio regular y el apoyo nutri-
cional cuantitativo sobre los indicadores de función inmune y el estado nutri-
cional de los pacientes en diálisis, se seleccionaron como sujetos de estudio
100 pacientes urémicos que se sometieron a tratamiento de hemodiálisis en
nuestro hospital desde febrero de 2021 hasta febrero de 2023. Se dividieron en
un grupo control (n=50) que recibió ejercicio regular y apoyo nutricional de
rutina y un grupo de investigación (n=50) que recibió ejercicio regular y apoyo
nutricional cuantitativo. Este estudio comparó los niveles basales de indicado-
res nutricionales como prealbúmina (PA), transferrina (TF), albúmina sérica
(SAB) y hemoglobina (HB); indicadores inmunes celulares tales como CD3+,
CD4+ y CD8+; así como indicadores inmunes humorales como inmunoglobuli-
na A (IgA), inmunoglobulina G (IgG) e inmunoglobulina M (IgM) al momento
de la inscripción y después de tres meses de intervención. En el momento del
reclutamiento, no hubo diferencias significativas en los indicadores nutriciona-
les entre los dos grupos de pacientes (p>0,05), ni en los niveles de indicadores
inmunes celulares (p>0,05) o indicadores inmunes humorales (p>0,05). Des-
pués de tres meses de intervención, los indicadores nutricionales como la PA en
todos los pacientes del experimento aumentaron (p<0,05), y los del grupo de
investigación superaron al grupo control (p<0,05). De manera similar, los nive-
les de CD3+ y otros indicadores inmunes celulares y las concentraciones de IgA
y otros indicadores inmunes humorales aumentaron en ambos grupos después
de tres meses de intervención (p<0,05). Sin embargo, estos aumentos fueron
mayores en el grupo de investigación que en el grupo control (p<0,05). El ejer-
cicio regular combinado con apoyo nutricional cuantitativo puede mejorar efi-
cazmente los niveles de índices nutricionales, el estado nutricional, los niveles
de índices inmunológicos y la función inmune de los pacientes en hemodiálisis.
Received: 09-12-2023 Accepted: 02-03-2024
INTRODUCTION
Hemodialysis (HD) is a renal replace-
ment therapy commonly used in patients
with advanced or end-stage renal disease.
Diabetes nephropathy accounts for a high
proportion of HD, which is consistent with
the increasing trend of the number of dia-
betes patients
1
. When the kidneys lose nor-
mal function, HD draws the patient’s blood
out of the body, simulates kidney function
through a special filter to remove waste,
toxins, and excess water from the body, and
then reinfuses the purified blood back into
the patient’s body to maintain water-electro-
lyte and acid-base balance. This process can
348 Kong and Zhu
Investigación Clínica 65(3): 2024
help patients maintain and improve their
quality of life
2
. However, at the same time as
treatment, patients may experience compli-
cations such as malnutrition
3
.
During the HD process, waste and excess
water in the patient’s body are discharged
through a dialyzer, which may increase the
patient’s metabolic rate and energy con-
sumption. Dialysis patients must limit their
intake of substances such as sodium, potas-
sium, and phosphorus during and between
treatment periods while also controlling
their water intake, which may lead to loss
of appetite and reduced intake. When energy
intake is insufficient to meet the patient’s
metabolic needs, it can lead to energy expen-
diture exceeding the intake, leading to mal-
nutrition
4
. During dialysis, some nutrients
and proteins may be removed along with the
waste, leading to protein loss. The inflam-
matory response and chronic inflammatory
state during dialysis may lead to metabolic
disorders, promote protein breakdown, ac-
celerate protein loss, and lead to malnutri-
tion
5
. The causes of HD malnutrition include
both iatrogenic and non-iatrogenic factors.
Possible factors related to iatrogenic factors
include poor dialysis adequacy and excessive
loss of serum albumin during dialysis, while
non-iatrogenic factors include poor appetite
and insufficient nutrition supplementation.
These factors can be changed and incorpo-
rated into the nutritional assessment
6
.
When dialysis patients are in a state of
severe metabolic stress, a sharp decrease in
serum albumin and a significant decrease
in albumin and hemoglobin are usually ob-
served. These changes are usually accompa-
nied by a deterioration in the overall health
status of patients and are unlikely to respond
to adjustments in dialysis plans. In such cas-
es, targeted nutritional interventions and
protein supplementation must be used dur-
ing dialysis
7
. Protein-energy malnutrition
and deficiency of single nutrients can affect
immune responses
8
. When immune cells are
activated, they can meet nutritional needs
through anaerobic respiration. Signals from
adipose tissue limit the activity and quantity
of immune cells in nutrient-deficient situa-
tions
9
. Under malnutrition, the secretion
of adipokines is dysregulated, affecting the
activity of immune cells and leading to an
increased susceptibility of inflammatory au-
toimmune reactions to infectious diseases
10
.
Long-term protein deprivation correlates
the degree of malnutrition in body weight
with the antibody response in the humoral
immune response
11
. Nutritional metabolism
is related to the differentiation and func-
tion of various immune cells, and nutritional
intervention can manipulate immune cell
function. Nutritional intervention can en-
hance nutritional status, affecting immune
cell dynamics
12
. This study applies regular
exercise combined with quantitative nutri-
tional intervention to HD patients and ana-
lyzes its effectiveness.
PATIENTS AND METHODS
General Information: The research
subjects of this study consisted of 100 ure-
mic patients who received HD treatment in
our hospital from February 2021 to February
2023. The patients knew the purpose of the
research, agreed to participate, and signed
an informed consent form. Inclusion crite-
ria: (a) Dialysis time≥6 months. (b) Age≥18
years old. (c) Regular dialysis 2-3 times a
week. (d) Comply with the diagnostic criteria
for malnutrition in the GLIM Malnutrition
Diagnostic Standards - Global Consensus Re-
port in Clinical Nutrition receive nutritional
support. (e) Stable conditions, electrolyte
disorders, acidosis, and other uremic signs
have been effectively controlled. Exclusion
criteria: (a) Concomitant acute gastrointes-
tinal diseases. (b) Concomitant malignant
tumors and other malignant consumptive
diseases. (c) Presented diseases that affect
metabolism, such as hyperthyroidism and
adrenal diseases. (d) Significant edema
of pleural and abdominal effusion. (e) The
combination of severe depression and recent
poor appetite that led to a decrease in body
Effect of regular exercise and quantitative nutritional support on dialysis patients 349
Vol. 65(3): 346 - 357, 2024
mass index. Other exclusion criteria: (a) de-
terioration of the condition or death during
the study. (b) Missing visits. (c) Automatic
exit. This study included 100 patients, with
no excluded cases. Upon meeting the inclu-
sion criteria, participants were randomly as-
signed into two groups to ensure compara-
bility and to minimize selection bias. Data
were systematically collected at two distinct
time points: baseline data at the beginning
of the study and follow-up data upon inter-
vention completion. Eighty valid data were
collected, and the effective data recovery
rate was 100%. There were no significant
differences in general information such as
gender, age, body mass index, and primary
disease between the two groups of patients
(p>0.05), as shown in Table 1.
Method: A nutritional assessment was
conducted on the included patients, and
their nutritional status was evaluated based
on the Malnutrition Universal Screening
Tool (MUST). BMI 20.0 was scored as 0.
A BMI between 18.5 and 20.0 was 1 point.
BMI 18.5 was 2 points, or weight loss with-
in 5% in the past 3-6 months was 0 points.
Weight loss between 5% and 10% in the
past 3-6 months was 1 point. Weight loss of
more than 10% in the past 3-6 months was 2
points. Fasting or consuming food less than
five days due to acute illness was 2 points.
A score of 0 indicates a low nutritional risk
state, and regular nutritional screening is
sufficient. A score of 1 indicated a moder-
ate nutritional risk state, requiring record-
ing dietary intake status within three days
and repeated screening. A score of 2 or more
indicated a high-risk state and required nu-
tritional intervention. After evaluation, the
patient’s BMI was ≤ 18.5, indicating a high-
risk state and requiring nutritional interven-
tion.
Control Group (CG): Regular exercise
combined with routine nutritional support.
Regular exercise: When patients came to the
hospital for treatment, exercise education
was carried out, and patients were advised to
take moderate walks indoors and outdoors
and engage in mild aerobic exercises such
as jogging, cycling, and swimming. Exercise
should be carried out 2 hours after meals,
and loose and breathable clothes suitable for
the ambient temperature should be worn.
Before and after exercise, measuring the
pulse and keeping records was necessary. If
there was any discomfort during exercise, it
should have to be stopped immediately, and
excessive exercise should be avoided. The
frequency of exercise was 3-5 times a week,
and the heart rate of exercise needed to be
20 times/min higher than the resting rate.
Each walk took 2-3 minutes and required
2-3 minutes of rest, with an average of 60-
80 steps per minute, alternating. Nutritional
support: Based on the patient’s condition
and dietary habits, it was essential to know
Table 1
Comparison of general information between two groups of patients.
Group n
Gender
Age (years)
BMI
(kg/m
2
)
Primary disease
Male Female
Chronic
glomerulonephritis
Diabetic
nephropathy
Polycystic
kidney
Other
Control
Group
50
28 (56)
22 (44)
56.56±12.36
18.49±3.21
13 (26)
15 (30)
11 (22)
11 (22)
Research
Group
50
30 (60)
20 (40)
57.12±12.40
18.50±3.20
14 (28)
14 (28)
10 (20)
12 (24)
χ
2
/t - 0.164 0.226 0.016 0.163
p - 0.685 0.822 0.988 0.983
Values are expressed as n (%) or X±SD.
350 Kong and Zhu
Investigación Clínica 65(3): 2024
how to correctly use scale tools such as salt
spoons and oil cups to help patients match
their daily meals and master nutritional sup-
port. Then, it was necessary to encourage pa-
tients to record and grasp their nutritional
intake. Weekly dietary surveys needed to be
conducted on patients, and timely guidance
and supplementation should be provided for
any unreasonable situation. It is also neces-
sary to correct unhealthy dietary habits and
adjust dietary plans.
Research group (RG): In the study, the
rRG received a comprehensive nutritional
intervention that included both a special-
ized nutrient formula and a tailored food
plan. The nutritional support was twofold:
(a) Specialized Nutrient Formula: The RG
was provided with a specially formulated oral
nutrient solution designed to meet the spe-
cific needs of hemodialysis (HD) patients.
The formula composition was based on indi-
vidual protein and energy requirements. Dai-
ly protein needs were calculated at 0.8 to 1.2
grams per kilogram of body weight. Energy
requirements for males and females were de-
termined using separate formulas: for males,
the formula used was 88.362 + (13.397 ×
weight in kg) + (4.799 × height in cm) -
(5.677 × age in years); for females, the for-
mula was 447.593 + (9.247 × weight in kg)
+ (3.098 × height in cm) - (4.330 × age in
years). The nutrient solution was composed
of a blend containing 1-9% protein, 1-20%
maltodextrin, 1-10% plant mixed oils, 0.1-
1% borage oil, 1-15% corn syrup solids, 1-5%
sugar, 1-2% cellulose, 0.1-1% essential min-
erals, 0.01-0.1% emulsifier, and 0.01-0.05%
L-carnitine and L-taurine. The RG members
were instructed to consume this nutrient
solution 200-250 mL per session, 6-7 times
daily, ensuring each feeding was completed
within 15-20 minutes and spaced at least two
hours apart. (b) Tailored Food Plan: In addi-
tion to the nutrient solution, patients in the
RG were provided with a food plan tailored
to their needs and dietary habits. This plan
was not solely based on the consumption of
the nutrient solution but was supplemented
by regular meals. The food plan aimed to en-
sure that patients received a balanced diet,
taking into account their daily total energy
and nutrient requirements. Fat intake was
targeted to provide 30% of the total daily
calorie intake, and carbohydrates were to
account for 50%. Patients were educated on
using tools like salt spoons and oil cups to
properly portion their meals and were en-
couraged to maintain a record of their nu-
tritional intake. Weekly dietary surveys were
conducted to offer personalized guidance
and to make any necessary adjustments to
their diet. (c) The combination of the nutri-
ent solution and the tailored food plan was
designed to ensure that patients in the RG
received adequate nutrition to address their
high-risk nutritional state, as identified by
the Malnutrition Universal Screening Tool
(MUST). Additionally, patients were advised
to consume fruit and vegetable juices be-
tween feedings, with a hydration goal of 500
mL of water plus the volume of the previous
day’s urine output. Weekly follow-ups via We-
Chat phone calls by nurses helped monitor
the patient’s adherence to the feeding regi-
men and provided an opportunity for ongo-
ing nursing guidance, including reminders
about the importance of nutrient tube main-
tenance and timely follow-up appointments.
Electronic records of follow-up data.
Outcome Measures
Nutritional status: At the time of en-
rollment, fasting peripheral venous blood
was collected from patients from 6:00 to
7:00 in the morning during the intervention
period of three months. After centrifuga-
tion, serum was collected for nutritional in-
dicators, including PA, TF, SAB, and HB. PA
standard reference range= 0.20-0.40 g/L.
TF’s typical reference range = 2.5-4.3 g/L.
SAB typical reference range = 35-55 g/L.
HB normal reference range=110~160 g/L.
Immunity
Cellular immune indicators: At the
time of enrollment, the patient’s fasting
Effect of regular exercise and quantitative nutritional support on dialysis patients 351
Vol. 65(3): 346 - 357, 2024
peripheral venous blood was collected from
6:00 to 7:00 in the morning for cellular im-
mune index testing during the intervention
period of three months. The detection in-
dicators include CD3+, CD4+, and CD8+.
The normal reference range for CD3+
was 955-2860/μL. CD4+normal reference
range= 450~1440/μL. CD8+ normal refer-
ence range= 320~1250/μL.
Humoral immune indicators: At en-
rollment, fasting venous blood was collected
from patients at 6:00 to 7:00 in the morn-
ing for humoral immune index testing dur-
ing the intervention period of three months.
The detection indicators include IgA, IgG,
and IgM, and the normal reference range of
IgA is 0.71-3.85 g/L. Normal reference range
of lgG =7.0-16.6 g/L. IgM typical reference
range = 0.4-3.45 g/L.
Statistical analysis: IBM SPSS 26.0®
was used for data processing, and the mea-
surement data was expressed as mean ± stan-
dard deviation (±SD). According to the Kol-
mogorov-Smirnov test, the measurement data
conformed to a normal distribution, with in-
dependent t-tests performed between groups
and paired t-tests performed within groups.
Graph Pad Prism 8 was used to draw a bar-
separated scatter plot of indicator horizontal
changes. The number of cases used in tech-
nical data, expressed as a percentage (n,%),
was subjected to the χ
2
test, and p<0.05 was
considered statistically significant.
RESULTS
Comparison of nutritional status between
the two groups of patients
At the time of enrollment, there was no
significant difference in the levels of PA, TF,
SAB, and HB nutritional indicators between
the two groups of patients (p>0.05). After
intervention for three months, the levels of
nutritional indicators such as PA in all pa-
tients in the experiment grew (p<0.05),
while the RG group exceeded the CG group
(p<0.05), as shown in Table 2.
Comparison of cellular immune indicators
between the two groups of patients
At the time of enrollment, there were
no significant differences in the levels of
cellular immune indicators such as CD3+,
CD4+, and CD8+ between the two groups of
patients (p>0.05). At the time of interven-
tion for three months, the levels of CD3+
and other cellular immune indicators in
both groups of patients increased (p<0.05),
while the RG exceeded the CG (p<0.05), as
shown in Table 3.
Table 2
Comparison of nutritional index levels between the two groups of patients.
Group n
PA (g/L) TF (g/L) SAB (g/L) HB (g/L)
Baseline
Parameters
At three
months of
intervention
Baseline
Parameters
At three
months of
intervention
Baseline
Parameters
At three
months of
intervention
Baseline
Parameters
At three
months of
intervention
Control
group
50
0.17±0.07
0.30±0.86
*
2.30±0.31
2.96±0.26
*
33.90±1.07
35.79±3.85
*
106.74±8.11
114.85±5.73
*
Research
group
50
0.16±0.07
0.34±0.57
*
2.30±0.33
3.15±0.40
*
33.74±1.06
37.11±2.17
*
104.82±6.27
117.44±5.16
*
t - 0.256 2.463 0.041 2.170 0.777 2.110 1.325 2.375
p - 0.799 0.016 0.968 0.032 0.439 0.037 0.188 0.020
PA: pre albumin. TF: transferrin. SAB: serum albumin. HB: hemoglobin.
Values are expressed as X±SD; *p<0.05 compared to levels at admission to the study.
352 Kong and Zhu
Investigación Clínica 65(3): 2024
Comparison of humoral immune indicators
between the two groups of patients
At the time of enrollment, a significant
difference did not exist in the concentration
of IgA, IgG, and IgM humoral immune indi-
cators between the two groups of patients
(p>0.05). At the time of intervention for
three months, the levels of IgA and other hu-
moral immune indicators in both groups of
patients increased (p<0.05), and the RG ex-
ceeded the CG (p<0.05), as shown in Table 4.
DISCUSSION
Prealbumin PA, also known as thyroid
binding protein, transports thyroid hor-
mones
13
. Its main synthetic organ is the liv-
er. In cases of malnutrition in the body, the
synthesis of PA is affected, and its blood level
decreases
14
. PA is often used as an essential
indicator to evaluate the nutritional status
of patients. During dialysis, HD patients ex-
crete a certain amount of protein through
dialysis, resulting in protein loss. The side
effects of medication, the disease itself, and
other factors in patients can lead to loss of
appetite and affect dietary intake. Patients
can also suffer malnutrition by limiting
phosphorus, sodium, and potassium intake
to control the fluid balance and avoid ma-
terial accumulation in the blood
15
. TF is a
protein responsible for iron transport, pres-
ent in plasma and involved in HB synthesis
and oxygen transport
16
. It absorbs iron from
Table 3
Comparison of cellular immune index levels between the two groups of patients.
Group n
CD3+(μL) CD4+(μL) CD8+(μL)
Baseline
Parameters
At three months
of intervention
Baseline
Parameters
At three months
of intervention
Baseline
Parameters
At three months
of intervention
Control
Group
50
944.74±21.05
974.04±24.64*
441.30±16.31
465.67±27.42*
313.38±14.93
364.68±20.60*
Research
Group
50
943.17±25.87
989.20±35.40*
442.11±18.57
479.95±27.49*
310.87±15.41
373.82±16.74*
t - 0.333 2.487 0.233 2.597 0.827 2.435
p - 0.740 0.015 0.816 0.011 0.410 0.017
Values are expressed as X±SD *p<0.05 Compared to the time of admission.
Table 4
Comparison of humoral immune index levels between the two groups of patients.
Group n
lgA (g/L) lgG (g/L) IgM (g/L)
Baseline
Parameters
At three
months of
intervention
Baseline
Parameters
At three
months of
intervention
Baseline
Parameters
At three
months of
intervention
Control
Group
50
0.70±0.06
1.26±0.09*
6.59±1.33
7.34±1.10*
0.39±0.05
1.57±0.08*
Research
Group
50
0.68±0.06
1.31±0.10*
6.44±1.21
7.94±1.22*
0.38±0.04
1.62±0.10*
t - 1.467 2.567 0.620 2.561 0.926 2.640
p - 0.146 0.012 0.537 0.012 0.357 0.010
IgA: Immunoglobulin A. LgG: Immunoglobulin G. IgM: Immunoglobulin M. Values are expressed as X±SD. *p<0.05
compared to Baseline Parameters.
Effect of regular exercise and quantitative nutritional support on dialysis patients 353
Vol. 65(3): 346 - 357, 2024
the intestines, spleen, and other tissues and
transports it to the RBC in the bone marrow,
synthesizing hemoglobin
17
. Iron metabolism
can be evaluated by monitoring the level of
TF in the blood. In cases of malnutrition, TF
can undergo a decrease
18
. SAB is a rich pro-
tein in the blood synthesized by the liver and
reaches the entire body through blood circu-
lation, maintaining a balance between plas-
ma and cells and avoiding the loss and reten-
tion of water and nutrients
19
. It participates
in the binding and transportation of various
substances, binds with free fatty acids, trans-
ports fatty acids to cells, participates in im-
mune regulation of the body, and maintains
acid-base balance
20
. Changes in SAB levels
can reflect the nutritional status of patients.
In HD patients with malnutrition, excessive
protein loss affects liver protein synthesis,
decreasing SAB levels
21
. HB is a Pro present
in RBC and an essential component in the
blood. It transports oxygen from the lungs to
various tissues for oxygen exchange
22
, and
HB levels are commonly used to assess the
degree of anemia in patients. Malnutrition
may cause anemia and decreased HB
23
. For
HD patients, long-term dialysis treatment
may lead to chronic inflammatory reactions
and iron loss, affecting RBC generation and
HB levels
24
.
Table 2 shows that regular exercise and
quantitative nutritional support can improve
patients’ nutritional indicators. Quantitative
nutritional intervention can develop person-
alized nutritional interventions based on the
specific nutritional needs of patients, ensur-
ing that patients consume sufficient Pro and
other nutrients. Pro is the primary raw mate-
rial for the synthesis of PA, and sufficient in-
take of Pro can promote the synthesis of PA.
Regular exercise can promote Pro synthesis
and increase muscle mass, which is the main
storage area for Pro. Increasing muscle mass
can increase Pro storage in the body. The
pro breakdown can lead to a decrease in PA
and transferrin levels. Regular exercise can
reduce Pro breakdown, and quantitative nu-
tritional interventions can increase Pro in-
take, thereby maintaining high Pro levels in
patients.
The effect of regular exercise and
quantitative nutritional intervention on
cellular immune indicators in HD mal-
nutrition patients. CD3+ is a cell surface
marker that refers to lymphocytes carrying
CD3 antigens. It mainly exists in the expres-
sion of T lymphocytes and is a part of T cell
receptor complexes. In immunology, cell
surface markers are identified and classified
to distinguish different types of immune
cells, and the number of T cells identified
by CD3 labelling can be monitored
25
. CD4+
cells, also known as helper T cells, are criti-
cal immune cells in the immune system and
influence the regulation and coordination
of immune responses in the body
26
. CD4+
are mainly present in the peripheral blood
and other parts of lymphatic tissue and par-
ticipate mainly in the immune response of
intracellular and extracellular pathogens,
as well as the immune regulation of T cells.
It suppresses the immune response through
inhibitory cytokines, avoiding excessive im-
mune response and autoimmune reactions
27
. CD8+ are cytotoxic T cells and essential
immune cells in the immune system. They
kill infected or mutated cells in the body
28
. When the body is invaded by pathogens
such as bacteria and viruses, CD8+ cells
can recognize and kill infected cells to pre-
vent pathogen transmission
29
. The activity
and function of CD8+ play a vital role in the
immune system, protecting the body from
pathogen infection and tumor invasion
30
.
The important subpopulations of lympho-
cytes play an essential role in the immune
response, and malnutrition may impact the
immune system, leading to impaired im-
mune function and affecting the level of
lymphocyte subpopulations. Thus, malnu-
trition can lead to a decrease in the num-
ber of T cells or impaired function, leading
to a decrease in the levels of CD3+, CD4+,
and CD8+, affecting the normal regulatory
function of the immune system
31
. Table 3
shows that regular exercise combined with
354 Kong and Zhu
Investigación Clínica 65(3): 2024
quantitative nutritional support can effec-
tively improve patients’ cellular and humor-
al immune indicator levels. Analyzing the
reasons, regular exercise combined with
quantitative nutritional intervention can
improve immune function and enhance the
number and activity of T cells, and regular
exercise can enhance the body’s immune
activity. Quantitative nutritional interven-
tion can provide T cells with the required
Pro and micronutrients, thereby increasing
cellular immune indicators such as CD3+
levels, helping to enhance T cell function
and immune response ability
32
.
The effect of regular exercise and
quantitative nutritional intervention on
humoral immune indicators in HD malnu-
trition patients. IgA is an immunoglobulin
mainly present on the surface of mucous
membranes and body fluids, mainly on the
surface of mucous membranes such as the
respiratory and digestive tracts. It is a barri-
er to protect the mucosa from pathogen in-
vasion and the first immune barrier. Abnor-
mal levels of IgA may be related to certain
immune diseases
33
. IgG is an immunoglob-
ulin in bodily fluids and blood, synthesized
by B lymphocytes and secreted during im-
mune activation during infection, mainly
involved in humoral immune responses. It
can bind to pathogens, neutralize toxins,
and activate the immune system, promot-
ing pathogen clearance and destruction
34
.
IgM is a crucial component of the humoral
immune system and is the immunoglobulin
first produced during early infection or ini-
tial exposure to antigens. It participates in
humoral immunity and can quickly initiate
immune responses, especially in early infec-
tions. It has a solid ability to agglutinate and
activate complement, quickly neutralizing
and clearing pathogens, thereby prevent-
ing the further spread of infection
35
. Pro
is the main component of immunoglobulin
36
. Due to an insufficient supply of Pro, mal-
nutrition patients limit immunoglobulin
synthesis, decreasing the levels of related
immunoglobulin indicators. Immunoglobu-
lin plays a crucial role in maintaining the
body’s immune function, and malnutrition,
leading to a decrease in immunoglobulin
synthesis, may increase the risk of infection
in patients. Therefore, providing reason-
able nutritional support for HD malnutri-
tion patients is crucial for improving their
immune indicators and preventing infec-
tion
37,38
. Regular exercise, combined with
quantitative nutritional intervention, could
markedly enhance the immune index levels
of patients, as shown in Table 4. Regular
exercise can stimulate immune cell activ-
ity and enhance the body’s ability to clear
pathogens. Quantitative nutritional sup-
port ensures patients receive sufficient Pro
supply through reasonable dietary adjust-
ments and nutritional supplementation, an
important immunoglobulin component. Re-
combinant Pro intake helps to increase the
synthesis of immunoglobulin.
In conclusion, this study observed a
significant effect of combining regular ex-
ercise with quantitative nutritional support
in improving the nutritional indicators of
HD malnutrition patients and also tested
the levels of humoral and cellular immune
indicators. The results show that regular
exercise combined with quantitative nutri-
tional support can also help improve im-
mune function and have an auxiliary thera-
peutic effect on the immune function of HD
malnourished patients. Its effect becomes
more pronounced with the extension of in-
tervention time. However, the sample size
of this study is relatively small, and the
specific efficacy needs to be confirmed by
expanding the sample size. Secondly, the
causes of malnutrition in dialysis patients
involve multiple factors and mechanisms.
This study only observed changes in nutri-
tional indicators and levels of humoral cel-
lular immune indicators, and its specific
mechanisms require further research in
animal experiments.
Effect of regular exercise and quantitative nutritional support on dialysis patients 355
Vol. 65(3): 346 - 357, 2024
ACKNOWLEDGMENT
We would like to acknowledge the in-
valuable contributions of all those who sup-
ported and assisted in this research.
Conflict of interest
No potential conflict of interest rele-
vant to this article was reported.
Funding
None
Authors’ ORCID number
Chunfeng Kong:
0000-0002-0163-3569
Changdong Zhu:
0000-0003-1350-5588
Contribution of authors
Both authors contributed equally to
this study, and their efforts were equally sig-
nificant in its completion.
REFERENCES
1. Elliott DA. Hemodialysis. Clin Tech Small
Anim Pract 2000;15(3):136-148. https://
doi.org/10.1053/svms.2000.18297.
2. Himmelfarb J, Ikizler TA. Hemodialysis.
N Engl J Med 2010;363(19):1833-1845.
https://doi.org/10.1056/nejmra0902710
3. Jameson MD, Wiegmann TB. Principles,
uses, and complications of hemodialysis.
Med Clin North Am 1990;74(4):945-960.
https://doi.org/10.1016/s0025-7125(16)
30528-4
4. Daugirdas JT. Hemodialysis adequa
-
cy and biocompatibility. Semin Dial
2011;24(5):508-509. https://doi.org/10.1
111/j.1525-139x.2011.00984.x
5. Graterol Torres F, Molina M, Soler-Ma
-
joral J, Romero-González G, Rodríguez
Chitiva N, Troya-Saborido M, Socias
Rullan G, Burgos E, Paúl Martínez J,
Urrutia Jou M, Cañameras C, Riera Sa
-
durní J, Vila A, Bover J. Evolving con-
cepts on inflammatory biomarkers and
malnutrition in chronic kidney disease.
Nutrients 2022;14(20):4297. https://doi.
org/10.3390/nu14204297
6. Sahathevan S, Khor BH, Ng HM, Gafor
AHA, Mat Daud ZA, Mafra D, Karupaiah
T. Understanding development of malnu
-
trition in hemodialysis patients: A Narra-
tive Review. Nutrients 2020;12(10):3147.
https://doi.org/10.3390/nu12103147
7. Piccoli GB, Lippi F, Fois A, Gendrot
L, Nielsen L, Vigreux J, Chatrenet A,
D’Alessandro C, Cabiddu G, Cupisti A.
Intradialytic nutrition and hemodialy
-
sis prescriptions: a personalized stepwi-
se approach. Nutrients 2020;12(3):785.
https://doi.org/10.3390/nu12030785
8. Munteanu C, Schwartz B. The relationship
between nutrition and the immune system.
Front Nutr 2022;9(1):1082500. https://
doi.org/10.3389%2Ffnut.2022.1082500
9. Wensveen FM, Valentić S, Šestan M,
Wensveen TT, Polić B. Interactions bet
-
ween adipose tissue and the immune sys-
tem in health and malnutrition. Semin Im-
munol 2015;27(5):322-333. https://doi.
org/10.1016/j.smim.2015.10.006
10. Carbone F, La Rocca C, De Candia P, Pro
-
caccini C, Colamatteo A, Micillo T, De
Rosa V, Matarese G. Metabolic control of
immune tolerance in health and autoimmu
-
nity. Semin Immunol 2016;28(5):491-504.
https://doi.org/10.1016/j.smim.2016.
09.006
11. Carrillo E, Jimenez MA, Sanchez C,
Cunha J, Martins CM, da Paixão Sevá
A, Moreno J. Protein malnutrition im
-
pairs the immune response and influen-
ces the severity of infection in a hamster
model of chronic visceral leishmaniasis.
PloS one 2014;9(2):e89412. https://doi.
org/10.1371%2Fjournal.pone.0089412
12. Okawa T, Nagai M, Hase K. Dietary
intervention impacts immune cell
functions and dynamics by inducing
metabolic rewiring. Front Immunol
2020;11(1):623989. https://doi.org/10.3
389/fimmu.2020.623989
356 Kong and Zhu
Investigación Clínica 65(3): 2024
13. Blake CC. Prealbumin and the thyroid hor-
mone nuclear receptor. Proc R Soc Lond B
Biol Sci 1981;211(1185):413-431. https://
doi.org/10.1098/rspb.1981.0015
14. Tekgüç H, Özel D, Sanaldi H, Akbaş H,
Dursun O. Prealbumin and retinol bin
-
ding proteins are not usable for nutri-
tion follow-up in pediatric intensive care
units. Pediatr Gastroenterol Hepatol
Nutr 2018;21(4):321-328. https://doi.
org/10.5223/pghn.2018.21.4.321
15. Chrysostomou S, Stathakis C, Petrikkos
G, Daikos G, Gompou A, Perrea D. As
-
sessment of prealbumin in hemodialysis
and renal-transplant patients. J Ren Nutr
2010;20(1):44-51. https://doi.org/10.10
53/j.jrn.2009.04.001
16. Gomme PT, McCann KB, Bertolini J.
Transferrin: structure, function and po
-
tential therapeutic actions. Drug Discov
Today 2005;10(4):267-273. https://doi.
org/10.1016/s1359-6446(04)03333-1
17. de Jong G, van Dijk JP, van Eijk HG.
The biology of transferrin. Clin Chim
Acta 1990;190(1-2):1-46. https://doi.
org/10.1016/0009-8981(90)90278-z
18. Sato M, Hanafusa N, Tsuchiya K, Kawa
-
guchi H, Nitta K. Impact of transferrin sa-
turation on all-cause mortality in patients
on maintenance hemodialysis. Blood Pu
-
rif 2019;48(2):158-166. https://doi.org/
10.1159/000499758
19. Fanali G, di Masi A, Trezza V, Marino M,
Fasano M, Ascenzi P. Human serum albu
-
min: from bench to bedside. Mol Aspects
Med 2012;33(3):209-290. https://doi.org/
10.1016/j.mam.2011.12.002
20. Fujiwara S, Amisaki T. Fatty acid bin
-
ding to serum albumin: molecular simu-
lation approaches. Biochim Biophys Acta
2013;1830(12):5427-5434. https://doi.
org/10.1016/j.bbagen.2013.03.032
21. Eriguchi R, Obi Y, Rhee CM, Chou JA,
Tortorici AR, Mathew AT, Kim T, Soohoo
M, Streja E, Kovesdy CP, Kalantar-Zadeh
K. Changes in urine volume and serum
albumin in incident hemodialysis pa
-
tients. Hemodial Int 2017;21(4):507-518.
https://doi.org/10.1111/hdi.12517
22. Gell DA. Structure and function of
haemoglobins. Blood Cells Mol Dis
2018;70(1):13-42. https://doi.org/10.10
16/j.bcmd.2017.10.006
23. Topal M, Guney I. The association of solu
-
ble Klotho levels with anemia and hemog-
lobin variability in hemodialysis patients.
Semin Dial 2023;36(2):142-146. https://
doi.org/10.1111/sdi.13122
24. Gilbertson DT, Hu Y, Peng Y, Maroni BJ,
Wetmore JB. Variability in hemoglobin le
-
vels in hemodialysis patients in the current
era: a retrospective cohort study. Clin Ne
-
phrol 2017;88(11):254-265. https://doi.
org/10.5414/cn109031
25. Chen Q, Yuan S, Sun H, Peng L. CD3(+)
CD20(+) T cells and their roles in human
diseases. Hum Immunol 2019;80(3):191-
194. https://doi.org/10.1016/j.humimm.
2019.01.001
26. Takeuchi A, Saito T. CD4 CTL, a cyto
-
toxic subset of CD4(+) T cells, their di-
fferentiation and function. Front Immunol
2017;8(1):194. https://doi.org/10.3389/
fimmu.2017.00194
27. Preglej T, Ellmeier W. CD4(+) Cyto
-
toxic T cells - phenotype, function and
transcriptional networks controlling
their differentiation pathways. Immu
-
nol Lett 2022;247(1):27-42. https://doi.
org/10.1016/j.imlet.2022.05.001
28. Natalini A, Simonetti S, Favaretto G, Pe
-
ruzzi G, Antonangeli F, Santoni A, Mu-
ñoz-Ruiz M, Hayday A, Di Rosa F. OMIP-
079: Cell cycle of CD4(+) and CD8(+)
naïve/memory T cell subsets, and of
Treg cells from mouse spleen. Cytometry
A 2021;99(12):1171-1175. https://doi.
org/10.1002/cyto.a.24509
29. Mittrücker HW, Visekruna A, Huber M.
Heterogeneity in the differentiation and
function of CD8
+
T cells. Arch Immunol
Ther Exp (Warsz) 2014;62(6):449-458.
https://doi.org/10.1007/s00005-014-
0293-y
30. Huff WX, Kwon JH, Henriquez M, Fetc
-
ko K, Dey M. The Evolving Role of
CD8(+)CD28(-) Immunosenescent T
cells in cancer immunology. Int J Mol
Effect of regular exercise and quantitative nutritional support on dialysis patients 357
Vol. 65(3): 346 - 357, 2024
Sci 2019;20(11):2810. https://doi.org/
10.3390/ijms20112810
31. Demas GE, Drazen DL, Nelson RJ.
Reductions in total body fat decrea
-
se humoral immunity. Proc Biol Sci
2003;270(1518):905-911. https://doi.org/
10.1098/rspb.2003.2341
32. Du F, Wu C. Review on the effect of exer
-
cise training on immune function. Biomed
Res In 2022;2022(1):9933387. https://
doi.org/10.1155/2022/9933387
33. Zemla A. LGA: A method for finding 3D
similarities in protein structures. Nu
-
cleic Acids Res 2003;31(13):3370-3374.
https://doi.org/10.1093/nar/gkg571
34. Liston A. The development of T-cell
immunity. Prog Mol Biol Transl Sci
2010;92(1):1-3. https://doi.org/10.1016/
s1877-1173(10)92001-2.
35. Cursiefen C, Bock F, Clahsen T, Regen
-
fuss B, Reis A, Reis A, Steven P, Heindl
LM, Bosch JJ, Hos D, Eming S, Gra
-
jewski R, Heiligenhaus A, Fauser S, Aus-
tin J, Langmann T. New therapeutic ap-
proaches in inflammatory diseases of the
eye - targeting lymphangiogenesis and
cellular immunity: Research Unit FOR
2240 Presents Itself. Klin Monbl Augen
-
heilkd 2017;234(5):679-685. https://doi.
org/10.1055/s-0043-108247.
36. Masiero A, Nelly L, Marianne G, Christo
-
phe S, Florian L, Ronan C, Claire B,
Cornelia Z, Grégoire B, Eric L, Ludovic
L, Dominique B, Sylvie A, Marie G, Fran
-
cis D, Fabienne S, Cécile C, Isabelle A,
Jacques D, Jérôme D, Bruno G, Katari
-
na R, Jean-Michel M, Catherine P. The
impact of proline isomerization on an
-
tigen binding and the analytical profile
of a trispecific anti-HIV antibody. MAbs
2020;12(1):1698128. https://doi.org/10.1
080%2F19420862.2019.1698128.
37. Pandey VK, Tripathi A, Srivastava S, Pan
-
dey S, Dar AH, Singh R, Duraisamy P,
Singh P, Mukarram SA. A systematic re
-
view on immunity functionalities and nu-
tritional food recommendations to develop
immunity against viral infection. Applied
Food Research 2023;3(1):100291. https://
doi.org/10.1016/j.afres.2023.100291.
38. Batool R, Butt MS, Sultan MT, Saeed F,
Naz R. Protein–energy malnutrition: A risk
factor for various ailments. Crit Rev Food
Sci Nutr 2015;55(2):242-253. https://doi.
org/10.1080/10408398.2011.651543.