Corresponding Author: Ramadan philosophy
E-mail: [email protected]
INTRODUCTION
According to Kidney
Disease Improving Global Outcomes (KDIGO) in 2012, CKD is defined as
abnormalities in kidney structure or function, for > 3 months, with
implications for health (Group, 2009). According to the Indonesian Renal Registry (IRR) in
2017, the proportion of the etiology or basic disease of CKD patients is hypertension
which ranks first at 36%, and diabetic nephropathy or known as diabetic kidney
disease is second place ((IRR), 2017). In chronic kidney disease (CKD) patients undergoing
hemodialysis, there is an increase in proinflammatory cytokines, including IL6,
CRP, Hepcidin, TNF -α, and Ferritin (Bacci et al., 2018) (Amore & Coppo, 2002).
Anemia is a common
complication of chronic kidney disease (CKD) and is associated with reduced
quality of life and increased morbidity and mortality (Portol�s et al., 2021).
Anemia is more frequent and severe at decreased
glomerular filtration rate (eGFR) (Fadhilah, 2016). Cross-sectional analysis of data from the National
Health and Nutrition Examination Survey (NHANES) in 2007-2008 and 2009-2010
revealed that anemia was twice as common in patients with CKD as in the general
population (15.4% vs. 7.6) (Zota et al ., 2014). The prevalence of
anemia increases with the development of CKD: 8.4% in stage 1 to 53.4% in stage
5.
Garlic has several bioactive compounds (Moulia, 2018).
The main organosulfur component of garlic is γ-glutamyl-S-alkyl-cysteine,
which can be hydrolyzed and oxidized to S-alkyl-cysteine sulfoxide (alliin).
Garlic extract has biological activity, especially as an anti-inflammatory and
antioxidant (Ried & Fakler, 2014) (El-Saber Batiha et al., 2020). A
previous study found that giving garlic extract to patients with chronic kidney
failure with CAPD reduced the proinflammatory cytokines IL-6 and TNF-α (Kendenan et al., 2021).
The anti-inflammatory and antioxidant effects of garlic are expected to improve
the degree of inflammation in CKD patients so that they can improve hemoglobin
levels. This study aims to assess the effect of garlic
extract on hemoglobin levels in patients undergoing chronic hemodialysis at
RSUP Dr. Mohammad Hoesin Palembang.
METHODS
This study used a Randomized,
Controlled, Double-Blind Crossover Trial design. This study was a crossover,
randomized, placebo-controlled, double-blind trial. The study subjects were 40
stages 5 CKD patients undergoing chronic hemodialysis, randomly divided into
two groups, namely the group that received 1000 mg of garlic extract per day
(2x500 mg) for six weeks and the group that received a placebo, then a 2-week
wash-out period. And after that, the two groups were given alternate treatment.
The study was conducted in the Hemodialysis Room of Dr. Moh Hoesin Hospital,
Palembang. Data collection was carried out in January 2022. Each subject
received informed consent before data collection. The inclusion criteria
included all chronic hemodialysis patients undergoing routine hemodialysis
twice a week with a duration of 4-5 hours each session, more than three months
and a maximum of 2 years, aged ≥18 years to 60 years, willing to
participate in the study by signing an informed consent form. Consent.
Exclusion criteria included patients suffering from acute infections, receiving
steroid therapy, suffering from autoimmune diseases, suffering from fluid
overload, being infected with Covid 19, and being allergic to garlic. Each
subject had blood drawn before hemodialysis after administering garlic extract
or placebo.
Sampling was carried out by blocking selection.
Patients who were going to undergo hemodialysis who met the inclusion criteria
were taken as samples with numbers 1,2,3,4 based on the order in which the
patients arrived until they met the specified number. Determining whether the model
was included in the garlic extract group or the placebo group was carried out
by a third party; the researchers and patients needed to learn.
All CKD patients undergoing hemodialysis
at the RSMH Hemodialysis Unit, fulfilling the inclusion criteria, and not
meeting the exclusion criteria, will be randomized into two groups, namely the
group that received garlic extract and the group that received placebo and then
examined in stages. Garlic extract medicine (allium sativum) 2x500 mg
capsules. This study consisted of two phases. In phase I, group A consisted of
20 samples that received garlic extract (from now on referred to as the garlic
group), and group B consisted of 20 pieces that received a placebo. The results
of both groups were observed for six weeks. This is followed by a 2-week
wash-out period. Then in phase II, group A and group B received the alternate
treatment.
Data processing and analysis using the
SPSS 25 for Windows program. The data is presented in the form of tables and
graphs. The information is tested to determine whether the distribution is
normal; if the distribution is normal, then parametric and non-parametric tests
are used if the data distribution is not normal. The data analysis plan will be
carried out in three stages: univariate, bivariate, and multivariate.
Univariate data is divided into numerical and categorical data. If numerical information
uses the Shapiro-Wilk normality test and Levine's homogeneity test, and if it
is normally distributed, then the data will be presented with the mean �
standard deviation. It will be presented with the median (min-max) if it is not
normally distributed.
The bivariate analysis will use the
chi-square test on categorical data. It will use a T-test (if normally
distributed) or Mann Whitney (if not normally distributed) on categorical and
numerical data and then paired T-test (if normally distributed) or Wilcoxon
test (if not normally distributed) to see analysis before and after treatment.
Multivariate will use post hoc analysis to analyze all independent and
confounding variables that correlate with the dependent variable in this study.
It is hoped that this confounding factor will not become a research bias.
RESULTS AND DISCUSSION
In
Table 1, 40 subjects participated, dominated by 23 men, of which 12 people
(60%) received garlic extract, while there were 17 women, of which eight people
(40%) received garlic extract. Garlic extract in phase 1. The
median age in the garlic group was 45.5(28-58) and 55(26-59) in the placebo
group.
Table 1. General characteristics
of research subjects
|
|
Group
|
|
Total
(n=40)
|
Garlic
(n=20)
|
Placebo
(n=20)
|
p.
s
|
|
Age
|
48.6 (26-59)
|
45.5 (28-58)
|
55 (26-59)
|
0.001
|
|
Gender
Man
Woman
|
23 (57.5%)
17 (42.5%)
|
12 (60 %)
8 (40 %)
|
11 (55 %)
9 (45 %)
|
|
p: p-value before and after treatment. p': p-value
after treatment between groups. a) Paired T-test b) Unpaired T-test,
significant if p<0.05
In Table 2. there is a significant difference in Hb levels in the
garlic group (p = 0.047), where the increase in Hb from 10.2 (9.2�11.8) mg/dl
to 10.23 (8.9�11 .6) mg/dl while in the placebo group, there was a decrease in
Hb from 10.18 (9.6 � 11.2) mg/dl to 10.05 � 0.52 mg/dl. Statistically, there
was a significant difference between Hb in the garlic and placebo groups after
treatment, with a p-value = 0.022.
Table 2. Characteristics of Hemoglobin
Levels
|
|
Group
|
|
Garlic (n=40)
|
Placebo (n=40)
|
p'
|
|
Before
|
After
|
p.s
|
Before
|
After
|
p.s
|
|
Hemoglobin
|
35.41 � 22.08
|
45.75 �
25.73
|
0.041a _
|
48.75 � 23.81
|
46.02 � 25.12
|
0.14a _
|
0.011b _
|
p: p-value before and after treatment. p': p-value after treatment
between groups. a) Paired T-test b) Unpaired T-test, significant if p<0.05
The mean
age of CKD patients undergoing chronic hemodialysis was 48.6 years, with the
proportion mostly male. The average age of CKD patients differs from data from
the Centers for Disease Control and Prevention (CDC), with an average age of 65
years (Hsu et al., 2016).
The difference in age in the placebo group (p=0.001) was signed between the
garlic extract group and the placebo group, but patients would be crossover so
that all subjects would receive the same treatment.
Based
on the results of previous studies, it was shown that there was an increase in
the proinflammatory cytokines IL-6, CRP, and Hepcidin in CKD patients
undergoing hemodialysis and was associated with decreased hemoglobin levels in
the subjects (Ibrahim et al., 2014). Other
studies suggest that increased levels of IL-6 correlate with the incidence of
anemia in subjects with CKD (Akchurin et al., 2019).
A
study showing patients with continuous ambulatory peritoneal dialysis (CAPD)
found a significant decrease in serum IL6 levels in 42 PD patients after eight
weeks of garlic extract administration (Zare et al., 2019).
Research showed that with continuous ambulatory peritoneal dialysis (CAPD) in
CKD patients, after giving 2x500 mg of garlic extract for six weeks, the results
showed a decrease in IL-6, which was significant with (p = 0.005) compared to
the placebo group (Kendenan et al., 2021).
In this study, it was found that garlic extract
can reduce the inflammatory process and can further increase hemoglobin levels
in CKD. In patients after giving onions, hemoglobin levels improved
significantly compared to the placebo. This study follows previous research
that hemoglobin is affected by inflammation, then patients undergoing
hemodialysis experience a process of continuous activation of proinflammatory
cytokines and an increase in proinflammatory cytokines such as CRP, TNF-α,
Ferritin, and Hepsidin as an anti-inflammatory and antioxidant, Garlic extract
plays an important role in reducing inflammation. According to research (Kendenan et al., 2021), there
is a decrease in IL-6. Research (Ibrahim et al., 2014) has that
CKD patients with high levels of IL-6, CRP, and Hepcidin are associated with
anemia in CKD. This study proved that after giving garlic extract 2x500 mg for six
weeks, there was an increase in hemoglobin levels in CKD patients with chronic
hemodialysis.
CONCLUSION
Based on the study's results, the following
conclusions are drawn from this study. There is effectiveness of garlic extract
in increasing hemoglobin levels in patients with stage V CKD undergoing chronic
HD at Moh Hoesin Hospital Palembang.
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