Discussion
We demonstrated that total and native thiol levels were significantly
lower in patients with CKD (stage 3-5) and patients receiving HD than
healthy subjects. However, disulfide levels were significantly higher
only in patients receiving HD. Moreover, TrxR enzyme levels were
significantly higher both in patients with CKD (stage 3-5) and patients
receiving HD than healthy subjects. Our study also revealed that IMA and
TOS levels were significantly higher in both CKD (stage 3-5) and HD
groups compare to controls. However, oxidative stress index (OSI) levels
which are calculated by TOS/TAS ratio were significantly higher only in
the HD group compare to control.
Coskun et al. showed that the native and total thiol levels of the
patients receiving HD treatment were significantly lower than the
control group. They hypothesize that low native and total thiol levels
occurred as a result of oxidative stress and chronic inflammation in HD
patients. In another study, Ates et al. reported that native and total
thiol levels were lower in HD patients compared to the control group and
they associated this decrease with the reduced total thiol reserves in
the organism [11].
In the same line with previous studies, we found that native and total
thiol levels in plasma samples of HD patients were lower than both CKD
and control groups. Our results were consistent with the literature. One
reason of the decrease in plasma thiol levels may be the continuous
depletion of sulfhydryl-containing antioxidant molecules, particularly
glutathione, to remove ROS as previously suggested [11]. However,
although the levels of glutathione as one of the antioxidants are known
to be high in the cell, the contribution of other low molecular weight
thiol compounds to the plasma sulfhydryl pool is relatively low compared
to albumin [14]. Therefore, reduced glutathione levels may not be
sufficient to explain the total thiol decrease alone in CKD (stage 3-5)
patients.
Another reason contributing to decrease in thiol levels can be explained
by the dynamic relationship between albumin and thiol balance. It is
known that albumin constitutes most of the thiol pool in plasma
(70-90%). Albumin is known to be irreversibly converted into end
products as a result of prolonged oxidative damage. One of these
albumin-transformed products is sulfenic acid (RSOH), which results in
an increase in the presence of oxidant, resulting in sulfinic
(RSO2H) or sulfonic (RSO3H) acid
formation, and these products have been suggested to
be removed from the circulation through the liver. We may speculate that
uremic toxins cause chronic elevation of oxidative stress in CKD
patients, albumin is exposed to a constant oxidative stress.
As a result, albumin may be irreversibly converted and withdrawn from
the circulation into oxidation products such as sulfenic, sulfinic, and
sulfonic acid as previously shown under long-term oxidative stress in
CKD patients. In addition, the liver’s depletion of plasma glutathione
and sulfhydryl sources due to this increased detoxification metabolism
may also contribute to low thiol depletion in plasma [12].
As it is well known, GFR is an important diagnostic and follow-up
parameter used in predicting renal function loss in renal diseases and
is used in the staging of CKD [4]. In this study, we examined the
correlations between thiol groups and GFR and found a positive and
strong correlation between both native and total thiol levels and GFR.
Plasma native and total thiol levels positively and highly correlated
with GFR which suggests that thiols can be used as a test parameter
related to disease prognosis in CKD patients.
We also evaluated the effect of HD session on native and total thiol
levels and disulfide parameters. Total and native thiol levels of
samples measured after dialysis were significantly higher compared to
the ones before dialysis. However, there was no significant difference
between two groups in terms of disulfide level after the correction with
albumin, there was no significant difference between the native and
total thiol values. On the other hand, the decrease in disulfide levels
of the samples after HD was statistically significant. In other words,
single HD session did not have a significant effect on total and native
thiols, but resulted in a significant decrease in disulfide levels. We
consider that volume correction, which may be caused by dialysis, may be
especially important in comparing thiol values associated with
albumin. In addition to that, this decrease in disulfide level may be
related to the regeneration of plasma thiol redox status by hemodialysis
as stated in the previous studies [10].
In the literature, there are only two studies evaluating the effect of
hemodialysis on plasma dynamic thiol balance by using Erel method
[10]. In these studies, a correction for a possible volume change
due to hemodialysis was not mentioned. It is known that during the HD
procedure, different degrees of hemoconcentration can occur in the blood
due to volume withdrawal from the patients after HD treatment. The
resulting increase in analyte concentrations which was proportional to
the volume withdrawn may be an important cause of interference,
especially for large molecular weight albumin or albumin-related
compounds. In the present study, unlike the previous two studies, we
determined albumin levels in blood against a possible hemoconcentration
before and after the dialysis. Albumin values were significantly higher
in the samples after the dialysis.
TrxR enzyme is a selenoprotein that effectively converts the oxidized
thioredoxin protein (Trx) to its reduced form. Therefore, they are
responsible for the regeneration of Trx and play a role in maintaining
the antioxidant effect. In the present study, increased serum TrxR
enzyme levels in CKD patients may be explained by the over-expression of
the enzyme to increase the antioxidant effect against increased
oxidative stress, as suggested in previous studies. As a result, serum
TrxR values were significantly higher in CKD (stage 3-5) and HD group
compared to healthy controls. This increase was more prominent in the HD
group.
IMA is a modified form of albumin due to oxidative stress. Elevated
plasma levels of IMA have been shown in diseases associated with
increased oxidative stress, particularly in ischemic heart disease
[23,24]. In this study, we found that IMA levels were higher in CKD
and HD groups compared to the control. However, there was no significant
difference between HD and CKD groups. In the literature, Turedi et al.
reported that IMA levels of patients receiving HD were found to be
higher compared to healthy controls [25]. In our study, in
accordance with the literature, increased IMA levels support the view
that increased oxidative stress may lead to albumin modification.