Translated from Indonesian to English - www.onlinedoctranslator.

com

ISSN 1978-2071 (Print); ISSN 2580-5967 (Online)

Wijaya Kusuma Medical Scientific Journal 10(1): 27-44, March 2021

Differences in Leukocyte and Lymphocyte Levels Post Parenteral

Vitamin B Combination in Patients with Chronic Kidney Disease
with Hemodialysis

Rizaldy Taslim Pinzon*, Ester Novitasari, Nining Sri Wuryaningsih

Duta Wacana Christian University Faculty of Medicine
Jl. Dr. Wahidin Sudirohusodo 5-25 Yogyakarta 55224, Indonesia
*e-mail: [email protected]

Abstract

Chronic kidney disease is a disease with progressive irreversible decline in kidney function with
various etiologies. Patients with chronic kidney disease are generally immunosuppressed and
susceptible to infection. Some of the causes are abnormalities in polymorphonuclear
leukocytes and lymphocytes. The results of several studies show that patients undergoing
hemodialysis have low levels of water-soluble vitamins. The decrease in the number of
leukocytes can also occur due to a decrease in neutrophils and lymphocytes which may be
caused by vitamin B6 and B12 deficiency due to hemodialysis. This study aims to measure
differences in leukocyte numbers, lymphocyte percentages, and absolute concentrations of
lymphocytes after administration of vitamins B1, B6, and B12 (combined vitamin B) in patients
with chronic kidney disease undergoing hemodialysis. This study is a study using a quasi-
experimental design method, One Group Pretest Posttest, on 115 selected patients. Patients
are given parenteral vitamins B1, B6, B12 every time they do hemodialysis, which is twice a
week which is given for 1 month during hemodialysis. The data taken in the form of leukocyte
numbers, percentage of lymphocytes, and absolute concentrations of lymphocytes. The
intervention given was in the form of parenteral administration of vitamins B1, B6, B12 to the
patient. After data collection, the leukocyte count, lymphocyte percentage and absolute
concentration of lymphocytes before and after the intervention were seen were examined and
then seen how the effect of parenteral administration of vitamins B1, B6, B12 on the leukocyte
count, lymphocyte percentage and absolute lymphocyte concentration in patients undergoing
hemodialysis. From the results of the study, there were 115 patients consisting of 72 men
(62.6%) and 43 women (37.4%). There was a difference in the form of a significant increase in
the mean leukocyte count at visit 1-2 with p-value = 0.033 after administration of B1, B6, and
B12. There was a change in the mean percentage of lymphocytes and the absolute
concentration of lymphocytes after administration of vitamins B1, B6, B12, but the changes
were not significant. and B12. There was a change in the mean percentage of lymphocytes and
the absolute concentration of lymphocytes after administration of vitamins B1, B6, B12, but
the changes were not significant. and B12. There was a change in the mean percentage of
lymphocytes and absolute concentration of lymphocytes after administration of vitamins B1,
B6, B12, but the changes were not significant.

Keywords: chronic kidney disease, vitamin B deficiency 1, B6, B12, changes in leukocyte and lymphocyte levels

1
 Difference in Levels of Leukocytes and Lymphocytes After Parenteral
Vitamin B Combination Administration in Patients with Chronic
Kidney Disease Undergoing Hemodialysis

Abstract

Chronic kidney disease is a disease in which kidney function decreases progressively

irreversibly with various etiologies. Patients with chronic kidney disease are generally
immunosuppressed and susceptible to infection. Some of the causes are abnormalities in
polymorphonuclear leukocytes and lymphocytes. The results of several studies indicate that
patients undergoing hemodialysis have low levels of water-soluble vitamins. A decrease in
the number of leukocytes can also occur due to a decrease in neutrophils and lymphocytes
which may be caused by deficiency of vitamins B6 and B12 due to hemodialysis. This study
aims to measure the difference in levels of leukocytes and lymphocytes after parenteral
vitamin B combination administration in patients with chronic kidney disease undergoing
hemodialysis This research is a quasi-experimental design, One Group Pretest Posttest, on
115 selected patients. Patients were given vitamin B1, B6, B12 parenterally every time
doing hemodialysis, twice a week given for 1 month during hemodialysis. The data were
taken in the form of leukocyte count, patient lymphocyte percentage, and absolute
lymphocyte concentration. The intervention of vitamins B1, B6, B12 was given parenterally
to the patient. After collect the data, the leukocyte counts, lymphocyte percentage and
absolute lymphocyte concentration before and after the intervention were seen, then it
was seen how the effect of parenteral administration of vitamins B1, B6, B12 on the
leukocyte count, lymphocyte percentage and absolute lymphocyte concentration in
patients undergoing hemodialysis. From the results of the study, there were 115 patients
consisting of 72 men (62.6%) and 43 women (37.4%). There was a difference and effect of
giving combination vitamin B in the form of a significant change in the mean number of
leukocytes at visits 1-2 with p-value = 0.033. There was a change in the mean of lymphocyte
percentage and absolute lymphocyte concentration after administering vitamins B1, B6,
B12 , but the changes were not significant.

Keywords: chronic kidney disease, deficiency of vitamins B1, B6, B12, changes in levels of
leukocytes and lymphocytes

PRELIMINARY ended in kidney failure. (Suwitra, 2014).

Chronic kidney disease is a disease Data from the Global Burden of Disease
with structural or functional damage to (GBD) in 2015 estimated that around 1.2
the kidneys and/or a decrease in the million people died from chronic kidney
glomerular filtration rate of less than 60 disease, this figure shows an increase of
mL/minute/1.73 that lasts more than 32% since 2005. Globally there were 697.5
three months. Chronic kidney disease million cases of chronic kidney disease in
results in a progressive decline in kidney 2017. 79 of 195
function, and in general
countries included in GBD had more than 1 is the most common type of leukocyte that
million cases of prevalence of chronic can decrease, so that a decrease in
kidney disease in 2017 (Bikbov et al, 2020) leukocytes can also occur (Wilson et al,
In general, patients with chronic 2017).
kidney disease are immunosuppressed and From the literature and previous
susceptible to infection, although research, it is suspected that patients with
leukocyte counts are often normal. Some chronic kidney disease may experience
of the causes are abnormalities in leukocyte and lymphocyte abnormalities.
polymorphonuclear leukocytes and Disorders of lymphocytes due to several
lymphocytes. Lymphocytes are the main things, namely the state of uremia,
key in the adaptive immune response exposure to the cephalon membrane
against pathogens that have successfully during hemodialysis, and vitamin B6
passed through natural immunity (Abbas deficiency that may occur if not assisted by
et al, 2016). supplements. A decrease in the number of
Results of several studies leukocytes can also occur due to a
showed that patients undergoing decrease in neutrophils and lymphocytes
hemodialysis had low levels of water- which may be caused by a deficiency of
soluble vitamins. One of the main causes is vitamins B6 and B12 due to hemodialysis.
due to the excessive loss of water soluble Therefore, researchers are interested in
vitamins in the dialysate. Vitamin B6 measuring differences in leukocytes and
deficiency causes atrophy of lymphoid lymphocytes after administration of
tissue, decreased number of lymphocytes vitamins B1, B6, and B12 (combination of
in lymph tissue, decreased antibody B vitamins) in patients with chronic kidney
production, also decreased lymphocyte disease undergoing hemodialysis.
proliferation and T cell toxicity (Donati et
al, 2002). In addition to vitamin B6, MATERIALS AND METHODS
vitamin B12 deficiency also causes a
Research design
significant decrease in the number of
The research design used is analytic with a
cytotoxic T cells and natural killer (NK)
quasi . method
cells that can affect lymphocyte numbers
(Mikkelsen et al, 2017). In vitamin B12
deficiency, neutrophils

experimental with one group pre and post test design. This research was conducted at
Bethesda Hospital and Panti Rapih intravenous B vitamins.
Hospital Yogyakarta which was carried out Each subject was given a
from August 2018 to October 2018. This combination of intravenous B vitamins,
study used laboratory data from the blood namely Neurobion Injection 5000
of patients with chronic kidney disease consisting of 100 mg vitamin B1, 100 mg
who underwent hemodialysis both before vitamin B6, and 5000 mcg vitamin B12.
and after the intervention. Patients were This vitamin is injected intravenously after
given parenteral intervention of vitamins each hemodialysis. Each subject who met
B1, B6, B12 every time they did the criteria was asked to sign an informed
hemodialysis, namely hemodialysis twice a consent form.
week and were given the intervention for The inclusion criteria in this study
1 month (a total of 8 times). were: patients with chronic kidney disease
Research subject undergoing hemodialysis at Bethesda
Sampling in this study used a consecutive Hospital and Panti Rapih Hospital
sampling technique and the number of Yogyakarta who were willing to take part
samples obtained was 115 people in the study and aged > 18 years. Exclusion
according to the inclusion and exclusion criteria in this study were: patients with
criteria. Each subject is given a acquired immunodeficiency such as
combination suffering from HIV/AIDS, and suffering
Administration of vitamin B combinationAdministration
injection of vitamin B combination injection
from malignancy, patients taking vitamins
B1, B6, B12 > 3 weeks.
After
Research Flow I hemodialysis 3-4 days
After Hemodialysis II
3-4
The first week Measurement
days Hemodialysis II
complete blood
(Visit 1) Administration of vitamin B combination injection

I hemodialysis Administration of
vitamin B
combination

Administration of B vitamins
injection combination After
3-4
Second week I hemodialysis Hemodialysis II
days

Administration of Administration of
vitamin B vitamin B
combination combination
 Blood measurement
complete (Visit 2)

After 3-4 days

The third week I hemodialysis Hemodialysis II

The fourth week

Administration of
vitamin B
combination
Complete blood
count (Visit 3)
 RESULTS

Table 1. Basic characteristics of respondents

Sample Characteristics n=115 %

Gender
Man 72 62.6
Woman 43 37.4
Age (Years), Mean ± SD
< 60 82 71.3
60 33 28.7
Diabetes mellitus
Yes 39 33.9
No 76 66.1
Hypertension
Yes 101 87.8
No 14 12.2
Cardiovascular Disease
Yes 31 27
No 84 73
Anemia
Yes 99 86.1
No 16 13.9

Table 2. Description of leukocyte number, lymphocyte percentage, absolute value of lymphocyte

concentration of research sample

Variable Visit 1 Visit 2 Visit 3

(Mean±SD) (Mean±SD) (Mean±SD)
Leukocyte count (/microLiter) 7096.00 ±2244.15 7495.82 ± 2369.15 7369.82 ±
2108.68
Lymphocyte percentage (%) 19.06 ± 7.00 19.13±7.60 18.48±7.51
Value of absolute lymphocyte 1286.33 ± 462.49 1362.02 ± 594.45 1317.69 ±
concentration 580.49
(x109/L blood)

Table 3. The results of the analysis of the leukocyte number, the percentage of lymphocytes, the
absolute value of the lymphocyte concentration of the
research sample

Variable Visit 1 – Visit 2 Visit 2 – Visit 3 Visit 1 – Visit 3

mean mean p-value mean mean p- mean mean p-value
± ± ± ± value ± ±
SD SD SD S SD SD
D
Number 7096.00 7495.82 ± 0.033 7495.82 ± 7369.82 ± 0.332 7096.00 ± 7369.82 0.068
leukocytes ± 2369.15 2369.15 2108.68 2244.15 ±
(/microLiter) 2244.15 2108.6
8
Lymphocyt 19.06 19.13 0.531 19.13 18.48 0.126 19.06 18.48 0.284
e ± ±7.6 ±7.6 ±7. ± ±7.
percentage 7.00 0 0 51 7.00 51
(%)
 Score
absolute 1286.33 ± 1362.02 ± 0.119 1362.02 ± 1317.69 ± 0.119 1286.33 ± 1317.69 0.530
concentration 462.49 594.45 594.45 580.49 462.49 ±
of lymphocytes 580.49
(x109/L blood)
To determine the relationship meaning.
between variables, a bivariate test was Wilcoxon's test on the percentage of
carried out using Wilcoxon because the lymphocytes showed an increase in the
data distribution was not normal using a average percentage of lymphocytes from
confidence value or a confidence level of visit 1 to visit 2 with a p-value = 0.531
95%. The mean or mean and median of this which indicated a non-significant change.
test shows the difference from visit 1 to The decrease in mean from visit 2 to visit 3
the next visit, while the p-value with a with p-value = 0.126 which indicates a non-
value of significant change. The decrease in mean
<0.05 indicates that the difference is from visit 1 to visit 3 with p-value = 0.284
significant. which indicates a non-significant change,
The results of the Wilcoxon test on In absolute lymphocyte
leukocyte numbers found an increase in concentration value, it was found that the
the average from visit 1 to visit 2 with a p- average increase from visit 1 to visit 2 with
value = 0.033 which indicated that there p-value = 0.119, which indicated that the
was a change in the form of a significant change was not significant. The decrease in
increase in the mean (p<0.05). At visit 2 the mean from visit 2 to visit 3 was with a
compared to visit 3, there was a decrease p-value = 0.119 which indicated a non-
in the mean with p-value = 0.332 which significant change. The increase in the
indicated that the change was not mean from visit 1 to visit 3 with a p-value =
significant. At visit 1 compared to visit 3, 0.530 which indicates a non-significant
there was an increase in the mean with p- change.
value = 0.068 which indicates no
Table 4. Description of leukocyte count with confounding variables
Leukocyte
Number
Variable Visit 1 – Visit 2 Visit 2 – Visit 3 Visit 1 – Visit 3
Mean± p-value median Mean± p-value median Mean± p-value median
SD SD SD
Gender
Ma -494.44 ± 0.559 -365.00 1.11 0.124 -20.00 -493.33 ± 0.121 -400.00
n 1561.73 ±1389.36 1605.61
Woman -241.39 ± -270.00 335.11 ± 380.00 93.72 ± 30.00
2013.47 1671.99 1999.83
Age (Year)
< 60 years -491.82 ± 0.099 -465.00 197.68 ± 0.323 300.00 -294.14 0.593 -250.00
old 1671.16 1692.33 ±1863.71
60 years -171.21 ± 280.00 -52.12 ± 20.00 -223.33 ± -120.00
1908.29 866.39 1569.47
 Leukocyte
Number
Variable Visit 1 – Visit 2 Visit 2 – Visit 3 Visit 1 – Visit 3
mean± p-value median mean± p-value median mean± p-value median
SD SD SD
Hypertensio
n
Yes -434.15 ± 0.309 -390.00 141.48 ± 0.596 220.00 -292.67± 0.248 -300.00
1760.51 1558.56 1826.85
No -152.14 ± 115.00 14.28 ± 255.00 -137.85 ± 480.00
1623.07 1051.02 1421.11
Diabetes mellitus
Yes -206.41 ± 0.535 -260.00 255.64 ± 0.444 270.00 49.23 ± 0.514 -130.00
1632.14 1912.35 2100.94
No -499.07 ± -400.00 59.47 ± 215.00 -439.60 ± -290.00
1795.29 1251.71 1576.49
Cardiovascular Disease
Yes -431.93 ± 0.857 -70.00 460.64 ± 0.157 470.00 28.70 ± 0.152 300.00
1784.79 1537.19 1824.27
No -387.97 ± -375.00 2.50 5.00 - -365.00
1733.98 ±1480.11 385.47±17
58.16
Anemia
Yes -423.63 ± 0.881 -360.00 82.82 ± 0.881 240.00 -340.80 ± 0.958 -210.00
1754.11 1494.35 1671.97
No -252.50 ± -145.00 393.12 ± -20.00 140.62 ± -480.00
1697.50 1576.94 2354.24

All confounding factors in this study not significant. At visits 1-3, there was an
did not have a significant relationship insignificant increase in the mean
(p>0.05) on the leukocyte count. At visit 1- leukocyte count in male sex variables, age
2 all variables experienced an increase in <60 years and 60 years, patients with
the average leukocyte count but did not comorbid hypertension and anemia. While
increase significantly. At visit 2-3, all the decrease in the mean leukocyte count
experienced a decrease in average except was not significant at visits 1-3 occurred in
for the age variable 60 years, which was an the female sex variable, patients with
increase in the mean leukocyte count but comorbid DM and cardiovascular disease.
Table 5. Description of lymphocyte percentage with confounding variables
Lymphocyte
Percentage
Variable Visit 1 – Visit 2 Visit 2 – Visit 3 Visit 1 – Visit 3
mean± p-value median mean± p-value median Mean±SD p-value median
SD SD
Gender
Ma -0.23±4.92 0.314 0.00 0.72 ± 0.475 0.00 0.48 ± 0.397 0.00
n 4.97 5.67
Woman 0.20±4.90 1.00 0.53 ± 0.00 0.74 ± 1.00
3.73 5.22
 Lymphocyte
Percentage
Variable Visit 1 – Visit 2 Visit 2 – Visit 3 Visit 1 – Visit 3
mean± p-value median mean± p-value median Mean±SD p-value median
SD SD
Age (Years)
< 60 years 0.51±4.16 0.064 1.00 0.96 ± 0.615 0.00 1.47 ± 0.004 1.00
old 4.47 5.06
60 years -1.51 ± -1.00 -0.12 ± 0.00 -1.63 ± -1.00
6.21 4.66 5.93
Hypertension
Yes -0.09 ± 5.10 0.784 1.00 0.68 ± 0.757 0.00 0.58 ± 0.898 0.00
4.64 5.60
No 0.14±3.13 0.00 0.42 ± 0.00 0.57 ± 0.50
3.77 4.68
Diabetes mellitus
Yes 0.07±5.02 0.864 0.00 0.05 ± 0.348 0.00 0.12 ± 0.291 -1.00
4.72 5.29
No -0.14 ± 4.87 1.00 0.96 ± 0.00 0.81 ± 1.00
4.42 5.60
Cardiovascular Disease
Yes -0.12 ± 4.50 0.884 1.00 1.12 ± 0.934 0.00 1.00 ± 0.997 0.00
4.68 6.00
No -0.04 ± 5.06 1.00 0.47 ± 0.00 0.42 ± 0.00
4.48 5.31
Anemia
Yes -0.10±5.09 0.871 1.00 0.70 ± 0.706 0.00 0.60 ± 0.881 0.00
4.67 5.74
No 0.12±3.63 1.00 0.31 ± 0.00 0.43 ± -0.50
3.64 3.65

In the relationship between cardiovascular disease and anemia. At visit

confounding factors and the percentage of 2-3, all of them experienced a decrease in
lymphocytes, it was found that there was a average except for the age variable 60
significant relationship (p<0.05) on one years, which was an increase in the average
confounding factor. In the age group <60 percentage of lymphocytes but not
years, a significant relationship was found, significant. At visits 1-3, all experienced a
namely the p-value = 0.004 at visits 1-3. At decrease in average except for the age
visit 1-2 most of the variables that variable 60 years, which was an increase in
experienced an increase in the average the average percentage of lymphocytes but
lymphocyte percentage but not significant not significant.
were male sex, age 60 years, comorbid
hypertension,
 Table 6. Description of absolute concentration of lymphocytes with confounding variables

Absolute Lymphocyte
Concentration
Variable Visit 1 – Visit 2 Visit 2 – Visit 3 Visit 1 – Visit 3
Mean± p-value median Mean± p-value median Mean± p-value median
SD SD SD
Gender
Ma -89.11 ± 0.260 -91.15 22.09 ± 0.737 45.70 -67.02 ± 0.044 -79.00
n 343.82 343.61 384.56
Woman -53.21 ± -44.20 81.56 ± 16.80 28.34 ± 71.40
436.10 326.70 383.08
Age (Years)
< 60 years -86.35 ± 0.990 -69.75 83.10 ± 0.055 51.50 -3.25 ± 0.136 6.20
old 395.60 335.68 401.24
60 years -49.20 ± 4.30 -52.01 ± -3.00 -101.21 ± -102.80
340.34 326.15 337.37
Hypertension
Yes -89.13 ± 0.342 -55.80 48.65 ± 0.402 50.80 -40.48 ± 0.521 -17.30
392.73 350.93 391.37
No 21.30 ± 36.25 13.13 ± 13.20 34.43± -21.60
254.44 220.17 342.20
Diabetes mellitus
Yes -24.11 ± 0.240 -24.70 8.79 ± 0.732 47.90 -15.31 ± 0.799 27.20
411.23 344.91 375.52
No -102.16 ± -82.95 62.56 ± 34.50 -39.59 ± -24.10
362.07 333.98 392.17
Cardiovascular Disease
Yes -74.24 ± 0.791 -62.60 99.70 ± 0.249 60.20 25.46 ± 0.575 0.60
303.00 291.28 349.30
No -76.22 ± -32.75 23.89 ± 13.95 -52.33 ± -46.90
405.70 352.02 397.45
Anemia
Yes -79.50 ± 0.583 -47.60 47.12 ± 0.502 47.90 -32.37 ± 0.910 -17.30
363.81 340.12 395.40
No -52.13 ± -45.50 27.03 ± -18.30 -25.10 ± -69.60
478.50 328.48 325.20

Most of the confounding factors in the average value of

this study did not have a significant
relationship (p>0.05), only one variable was
found to have a significant relationship
with the absolute concentration of
lymphocytes. At visits 1-3, it was found
that a significant relationship was found in
the male sex variable, which showed a
significant change in the mean absolute
concentration of lymphocytes. At visit 1-2
absolute concentration of lymphocytes age group 60 years. And at visits 1-3 there
in all confounding variables increased was an increase in the mean absolute
but not significant. At visit 2-3 there concentration of lymphocytes in all
was a decrease in the mean absolute confounding variables except in patients
concentration of lymphocytes in all with cardiovascular comorbidities.
confounding variables except for the

DISCUSSION 33 subjects in this study were elderly. Kidney

In this study the distribution of function declines with aging. The amount of

respondents by gender, it can be seen that age-related decrease in GFR differs between
there are 72 male respondents and 43 ethnic groups (Iseki, 2008). In the general

female respondents. This shows that there population, older age

are more male respondents than female
subjects. Decreased kidney function occurs
more rapidly in men than women due to
the protective effect of the hormone
estrogen and the deleterious effect of
testosterone as well as differences from an
unhealthy lifestyle (Carrero et al, 2018).
Another effect of sex hormones is that
testosterone also induces the renin-
angiotensin system and is inhibited by
estrogen, estrogen also plays a role in
reducing oxidative stress in the kidneys by
suppressing NADPH oxidase activity
(Carrero et al, 2018).
The mean age of the subjects in this
study was 51.58+12.51 years. This is similar
to a study conducted by Cruz et al (2011)
that the mean age of patients undergoing
hemodialysis was 52.5 ± 15.9 years. In this
study, there were 82 people aged <60
years and
33 people aged 60 years. This shows that
associated with decreased GFR and GFR in women (Chang et al, 2016).
have a higher prevalence of The normal leukocyte count for
albuminuria, cardiovascular disorders, young adults is 4500-11000/mm³. The data
hypertension, diabetes, and other risk from this study showed that the leukocyte
factors for kidney disorders (Hallan et counts of the study samples at visits 1, 2,
al, 2012). and 3 were at normal values. The mean
Previous studies have shown leukocyte count at visit 1 was 7096.00 ±
that women have a systolic pressure of 2244.15 /mm³, visit 2 was
10 mmHg lower than men. Blood 7495.82 ± 2369.15 /mm³, and visit 3 is
pressure is known to be one of the of 7369.82 ± 2108.68 /mm³. The increase in
main determinants of the the number of leukocytes occurred at visit
development of atherosclerosis and 1 to visit 2 and visit 1 to visit 3, while the
the development of end-stage renal decrease occurred at visit 2 to visit 3.
disease, so differences in systolic blood Based on statistical tests on all
pressure between sexes may respondents in this study, it was found that
contribute to slowing the decline in

the change was in the form of an increase and loss of vitamins on dialysis. Vitamin
in the mean leukocyte count after the deficiency mainly occurs in water soluble
intervention of vitamins B1, B6, B12 at visit vitamins which include vitamins B1, B6, B12.
1-2 significantly with a p-value = 0.033. This Decreased appetite related to dietary intake
shows that the administration of vitamins occurs due to high plasma leptin levels and
B1, B6, B12 at visit 1-2 plays a role in inflammation that causes the production of
increasing the mean leukocyte count. anoregenic cytokines (Elia et al, 2013).
Meanwhile, at visits 2-3 and visits 1-3, Administration of B vitamins1, B6 and B12 in this
study can be seen to have increased the number of respondents'
there was no significant change in the
lymphocytes, especially at the 3rd visit, which is after one month of vitamin
mean leukocyte count (p-value> 0.05). administration. Vitamin B6 is useful and acts as a glutathione precursor to
become an antioxidant, especially
Patients on renal replacement
therapy in general often experience
decreased levels of vitamins that can affect
white blood cell counts. Decreased
vitamins can occur due to inadequate
dietary intake, decreased gastrointestinal
absorption, abnormal renal metabolism,
in patients with chronic kidney immunity (Abbbas et al, 2016).
disease. In patients with chronic Lymphocytes are the most common type of
kidney disease, the state of uremia white blood cell after neutrophils. The
also plays a role in decreasing food percentage of normal lymphocytes is 20% -
intake. This causes the possibility of 40%. The results of this study showed that
vitamin deficiency, so it is necessary to the average lymphocyte percentage of
be given vitamin supplementation patients with kidney disease at visit 1
including vitamins B1, B6 and B12. (Elia (19.06%), visit 2 (19.13%), and visit 3
et al, 2013) (18.48%) was below the normal value of
Patients with chronic kidney lymphocyte percentage.
disease generally have decreased The average lymphocyte percentage
immunity compared to normal people. at visit 1-2 experienced a slight increase in
Lymphocytes are one type of the average of 0.7%, but there was a
leukocytes that function as an immune decrease in visits 1-
system. There are two types of 3. The total decrease in percentage from
lymphocytes, namely T-cell visit 1 (19.06%) to visit 3 (18.48%) was
lymphocytes and B-cell lymphocytes. B 0.58%. Based on the results of statistical
cells play a role in humoral immunity tests, there was no significant change in
and T cells play a role in cellular the percentage of lymphocytes at all visits.
This matter

showed that the administration of vitamins which will affect the body's resistance
B1, B6 and B12 did not give a significant (Dalrymple and Go, 2008). This is also
change in the percentage of lymphocytes, consistent with previous research which states
which could be caused by the that in patients with chronic kidney disease
administration of vitamin B combinations found a low number of neutrophils, B and T
that were too short, namely 4 weeks of lymphocytes and hemodialysis processes can
parenteral administration of vitamins. increase B and T lymphocyte apoptosis (Saad et
The results of this study are in al, 2014).
accordance with the theory presented by In a previous study conducted by Atziza
Dalrymple and Go that in ESRD patients (2015) regarding the difference in the mean
there is a disturbance in lymphocyte pre- and post-hemodialysis lymphocyte levels,
function so that they will experience a it was found that the average pre-hemodialysis
deficit in the percentage of lymphocytes lymphocyte level was 1969 ± 729.11 and post-
hemodialysis was 1397. The hemodialysis process produces a
± 545.23, this indicates that there is a complex response that causes defects in
decrease in the value of the respondent's the lymphocyte membrane and decreases
lymphocyte levels after hemodialysis the life span of lymphocyte cells in the
(Atziza et al, 2017). This can occur because body so that it is associated with a
the blood is in contact with the surface of decrease in the immune system. In
the dialyzer membrane during addition, the decrease in immune response
is due to suppression of cell mediated
immunity caused by shortening of
lymphocyte lifespan, lymphopenia,
inhibition of lymphocyte transformation,
and suppression of T lymphocyte activity
which leads to changes in the number and
function of lymphocytes (Lisoswka et al,
2016; Donati et al, 2016). 2002).
The absolute concentration of
lymphocytes has a reference interval of
1.0-4.8 (x109/L of blood) in adults. Overall
results have normal values or are within
the reference interval. The mean absolute
concentration of lymphocytes increased
from visit 1 (1286.33 ± 462.49 x109/L of
blood)
to visit 2 (1362.02 ± 594.45 x109/L blood),
a slight decrease from visit 2 to visit 3
(1362.02 ± 594.45 x109/L blood), and
increase from visit 1 (1286.33 ± 462.49
09/L blood) to visit 3 (1317.69 ± 580.49
x109/L blood). However, based on
statistical tests, the administration of
vitamins B1, B6, and B12 had no significant
effect (p-value > 0.05) on the change in the
mean concentration of lymphocyte
asbolutes at all visits. The final results concentration of lymphocytes
showed an increase in the absolute

marked by a higher number on the 3rd Previous studies showed the benefits
visit, namely 1317.69 (x109/L of blood) of supplementation of folate (5 mg) and
compared to the 1st visit of 1286.33 vitamin B6 (250 mg) also resulted in a
(x109/L of blood). The total increase in decrease in homocysteine concentrations,
absolute concentration of lymphocytes was improvement in lipid profile and symptoms
31.36 (x109/L of blood). of peripheral polyneuropathy and reduced
Vitamin B6 has an important role in calcium oxalate formation in patients
antioxidant defense through the formation treated with hemodialysis (Ziakka et al,
of cysteine which is a precursor of 2001). Administration of vitamin B6 doses
glutathione synthesis. Glutathione has a of 50 to 100 mg/day can be of great
role in lymphocyte proliferation and therapeutic value in hemodialysis patients.
antioxidant defense system. Increased In the immune system, vitamin B12
production of oxidants can cause damage functions in regulating the immune system,
to healthy tissues in the body. Vitamin B6 as an immunomodulator in cellular
deficiency can cause disorders of lymphoid immunity and is involved in cell division.
tissue, decreased lymphocytes in the Research shows that vitamin B12
lymph nodes and spleen, and decreased deficiency causes a significant decrease in
total lymphocyte counts. the number of cytotoxic T cells and natural
Vitamin B6 is also critically needed killer (NK) cells (Mikkelsen et al, 2017).
for vitamin B12 absorption and niacin Administration of vitamin B12 in patients
synthesis. In addition, it can inhibit platelet with vitamin B12 deficiency facilitates the
aggregation, and improve the development production of T lymphocytes, cellular
of diabetic neuropathy (Metz et al, 2003; immunity and maintains the number of
Kobzar et al, 2009). On the other hand, subgroups of lymphocytes within the
vitamin B6 . deficiencyimpair lymphocyte normal range (Lewicki et al, 2014).
maturation, growth Genomic damage in peripheral blood
and proliferation, and the production of lymphocytes of dialysis patients is caused
antibodies that suppress Th1 production by oxidative stress. Stress can be
and cytokines, thereby, promoting a Th2 ameliorated by supplementation of folic
response (Maggini et al, 2007). acid and vitamin B12 which is thought to
contribute to the reduction of homocystine
(Stopper et al, 2008). infection, oxidative stress,

and inflammation have been shown to function. The ability of the immune system in
reduce responsive toagent the elderly group will
stimulant erythropoiesisby
increasing release of
proinflammatory cytokines. Stress
oxidative stress and inflammation can
occur weakened by vitamin B12
and folic acid
supplementation (Stenvinkel, 2003). This
study also tested statistical data between
leukocyte count, lymphocyte percentage
and absolute concentration of lymphocytes
with confounding variables. Most of the
results obtained are notsignificant that is p-
value> 0.05. On Testing the
absolute concentration of lymphocyte data
at visits 1-3 based on gender obtained
significant results with p-value = 0.044. In
testing the lymphocyte percentage data at
visits 1-3 there are significant results in the
age category
with p-value = 0.004.
Decrease in kidney function on a
small scale is a normal process with age but
does not cause abnormalities if it is still
within normal limits and can be tolerated
by the kidneys and body. One of the factors
that decrease kidney function is age,
because with increasing age, kidney
function decreases and is also associated
with a decrease in the rate of glomerular
excretion and worsening of renal tubular
decreases with increasing age, percentage of lymphocytes and the
including in terms of the speed of the absolute concentration of lymphocytes
immune response against this chronic after the administration of vitamins B1, B6,
kidney disease infection, because in and B12 have not been studied. happened
the elderly the production of significantly. This study also did not have a
immunoglobulins will also decrease treatment control group (not given
(Hasdinah et al, 2014). vitamins).
LIMITATIONS OF THE RESEARCH
This study was conducted with a CONCLUSION
short duration of 4 weeks and the Administration of B vitamins1, B6, and B12
in this study proved safe. There were no side effects of drug
administration of a combination of B
administration in all study subjects. There was a difference in the
vitamins was only given 2x a week form of a significant increase in the mean leukocyte count at visit 1-
2 with p-value = 0.033 after administration of B1, B6, and B12. There
every time on hemodialysis. Therefore,
was no significant difference after administration of vitamins B1, B6,

changes in the form of an increase in B12 to the mean percentage of lymphocytes and absolute
concentration of lymphocytes. Provision of vitamins B1, B6, and B12
the average leukocyte number, the based on the results of this study

still not enough to be input as therapy in Kidney Failure Patients. medulla. 7(4):
patients with chronic kidney disease 37-41.
undergoing hemodialysis, so further Bikbov B, Purcell CA, Levey AS, Smith M, Abdoli
research is needed with a larger sample A, Abebe M, et al. 2020. Global,
size to consider the administration of Regional, and National Burden of
vitamin B combinations as adjunctive Chronic Kidney Disease, 1990–2017: A
therapy in patients with chronic kidney Systematic Analysis for The Global
disease. Burden of Disease Study 2017. The
Lancet. 395: 709–

REFERENCES 733.

Abbas A, Lichtman A, Pillai S, 2016. Basic Carrero J, Hecking M, Chesnaye N, Jager K,

Immunology of Abbas: Functions 2018. Sex and Gender Disparities in

and Abnormalities of the Immune The Epidemiology and Outcomes of

System. 5th ed. Elsevier, Chronic Kidney Disease. Nature

Singapore. Reviews Nephrology. 14(3): 151-164.

Atziza R, Ayu P, Yonata A, 2017. Differences

in Pre and Post Hemodialysis
Lymphocyte Levels in Chronic
Chang P, Chien L, Lin Y, Wu M, Chiu W, Mahmoodi B, Black C, Ishani A, et
Chiou H, 2016. Risk Factors of al, 2012. Chronic Kidney Disease
Gender for Renal Progression Prognosis. Age and Association of
in Patients with Early Chronic Kidney Measures with Mortality
Kidney Disease. Medicine. and End-stage Renal Disease.
95(30): e4203. JAMA. 308(22): .2349.
Dalrymple L, Go A, 2008. Epidemiology Hasdinah HR, Dewi P, Peristiowati Y, Imam
of Acute Infections Among S, 2014. Immunology - Diagnosis
Patients With Chronic Kidney and Molecular Biology
Disease. Clinical Journal of Techniques. Nuha Medika,
the American Society of Yogyakarta.
Nephrology. 3(5):1487-1493. Iseki K, 2008. Gender differences in chronic
Elia M, Ljungqvist O, Stratton R, kidney disease.
Lanham- New S, 2013. Clinical Kidney International,
nutrition. 2nd ed. Wiley- 74(4): 415-417.
Blackwell, John Wiley & Sons, Kobzar G, Mardla V, Rätsep I, Samel N,
Oxford. 2009. Effect of vitamin B(6)
Hallan S, Matsushita K, Sang Y, vitamers on platelet aggregation.
Platelets. 20(2): 120-124.

Lewicki S, Lewicka A, Kalicki B, Kłos A, Regulatory T Cells in End-Stage Renal

Bertrandt J, Zdanowski R. 2014. Disease Patients. Inflammation
Experimental Immunology The Research. 63(2): 99-103.
Influence of Vitamin B 12 Maggini S, Wintergerst ES, Beveridge S, Hornig
Supplementation on The Level of DH, 2007. Selected Vitamins and Trace
White Blood Cells and Elements Support Immune Function
Lymphocytes Phenotype in Rats by Strengthening Epithelial Barriers
Fed a Low-Protein Diet. Central and Cellular and Humoral Immune
European Journal of Immunology. Responses. British Journal of Nutrition.
419-425. 98(S1): S29-S35.
Lisowska K, Dębska-Ślizień A, Jasiulewicz A, Metz T, Alderson N, Thorpe S, Baynes J, 2003.
Bryl E, Witkowski J, 2013. Pyridoxamine, an Inhibitor of
Influence of Hemodialysis on Advanced Glycation and Lipoxidation
Circulating CD4lowCD25 high Reactions: A Novel Therapy for
Treatment of Diabetic Mikkelsen K, Stojanovska L, Prakash M,
Complications. Archives of Apostolopoulos V, 2017. The
Biochemistry and Biophysics. Effects of Vitamin B on The
419(1): 41-49. Immune/Cytokine Network and
TheirInvolvementin
depression. Maturity. 96:58-71.
Saad K, Elsayh K, Zahran A, Sobhy K, 2014.
Lymphocyte Populations and
Apoptosis of Peripheral Blood B
and T Lymphocytes in Children
With End Stage Renal Disease.
Renal Failure. 36(4): 502-507.
Stenvinkel P, 2003. Anaemia and
Inflammation: Ahat are The
Implications for The Nephrologist.
NephrologyDialysis
Transplants.
Stopper H, Treutlein AT, Bahner U, Schupp
N, Schmid U, Brink A, et al, 2008.
Reduction of the Genomic
Damage Level in Haemodialysis
Patients by Folic Acid and Vitamin
B12 Supplementation. Nephrology
Dialysis Transplantation. 23(10):
3272–3279.
Suwitra K, 2014. Chronic Kidney Disease. In:
S. Setiati, I. Alwi, A. Sudoyo, M.
Simadibrata, B. Setiyohadi and A.
Syam, ed., Textbook of Internal
Medicine Volume II, 6th ed.
Jakarta: InternaPublishing, pp.
2161-2167.
Wilson C, Vergara-Lluri M, Brynes R, 2017.
 Evaluation of Anemia, Leukopenia,
and Thrombocytopenia. In: E. of Vitamin B6 and Folate
Jaffe, D. Arber, E. Campo, N. Supplementson Plasma
Harris and a. Quintanilla-Martinez, Homocysteine and Serum Lipids
ed., Hematopathology, 2nd ed. Levels in Patients on Regular
Elsevier, Philadelphia. 195-234. Hemodialysis.
Ziakka S, Rammos G, Kountouris S, International
Doulgerakis C, Karakasis P, Urology and Nephrology. 33(3):
Kourvelou C, et al, 2001. The 559–562.
Effect