Objectives: To evaluate the relationship between serum iron and ferritin concentrations with some characteristics of chronic kidney diseases. Subjects and methods: A cross-sectional study with a study group of 124 stage 3 - 5 chronic kidney disease patients, and a control group of 66 healthy people at Department of Nephrology and Hemodialysis, 103 Military Hospital.
Trang 1SURVEY ON THE RELATIONSHIP BETWEEN SERUM
CONCENTRATION OF IRON, FERRITIN AND SOME CHARACTERISITICS IN PATIENTS WITH STAGE 3 TO 5
CHRONIC PREDIALYSIS KIDNEY DISEASE
Nguyen Van Hung 1 , Nguyen Cao Luan 2 ; Le Viet Thang 3
SUMMARY
Objectives: To evaluate the relationship between serum iron and ferritin concentrations with
some characteristics of chronic kidney diseases Subjects and methods: A cross-sectional study
with a study group of 124 stage 3 - 5 chronic kidney disease patients, and a control group of
66 healthy people at Department of Nephrology and Hemodialysis, 103 Military Hospital
Results: The mean concentrations of serum iron in study group was significantly lower than control
group (10.7 µmol/L versus 15.81 µmol/L), but the mean concentrations of serum ferritin in study
group was higher than control group (403.73 ng/mL versus 198.45 ng/mL) with p < 0.01 Serum
ferritin concentration was significantly related with the stage of chronic kidney diseas (p < 0.05)
Iron level was positively correlated with serum creatinine level (r = 0.201; p < 0.05) and negatively
correlated with hs-CRP level (r = -0.229; p < 0.05) Conclusion: Patients with stage 3 - 5 chronic
kidney diseas, predialysis had lower serum iron and higher serum ferritin concentrations than control
group There were significant correlations between serum iron with serum creatinine concentrations
and hs-CRP levels
* Keywords: Chronic kidney disease; Serum iron; Serum ferritin
INTRODUCTION
Anemia of chronic kidney disease
(CKD) is widely prevalent in patients with
renal impairment and is associated with
significant morbidity and mortality [6]
Deficient erythropoietin (EPO) production
and reduced bioavailability of iron ultimately
lead to absolute or functional iron deficiency
anaemia Anaemia of end-stage renal
disease can be managed relatively
successf ully by recombinant human
erythropoietin Iron administration plays a central role in enhancing anaemia responsiveness to EPO Serum ferritin concentrations and iron saturation ratio are among the two most commonly used markers of iron status in maintenance dialysis patients [1, 5] Absolute iron deficiency, the iron deficiency that is characterized by low or absent bone marrow staining for iron, is distinguished
from functional or relative iron deficiency,
1 Transport Hospital
2 Bachmai Hospital
3 103 Military Hospital
Corresponding author: Nguyen Van Hung (hunggttw@gmail.com)
Trang 2which is defined as a response to
intravenous iron with an increase in
hemoglobin (Hb) or a decrease in
erythropoiesis-stimulating agent (ESA)
requirement [9] Therefore, we conducted
this research in order: To find the
relationship between serum iron, ferritin
concentrations and stage of CKD, serum
creatinine and hs-CRP level
SUBJECTS AND METHODS
1 Subjects
The study was conducted with a study
group of 124 stage 3 - 5 chronic kidney
diseas (CKD) patients, prediaysis and
a control group of 66 healthy people
at Department of Nephrology and
Hemodialysis, 103 Military Hospital
* Criteria exclusion: Blood transfusion,
active bleeding, some acute diseases,
undergoing surgery within 3 months prior
to study period; taking iron products
within last 7 days; did not agree to participate in the study
2 Methods
* Study design: A cross-sectional
descriptive study
* Serum iron concentrations measurement:
Quantification of serum iron concentrations
by color comparison following the principle: Fe3+ is released from the transferrin-Fe complex at pH < 2.0; Fe3+ in the acid environment will be reduced to Fe2+ Fe2+ combine with ferrozine buffers to form a color complex After that, the test is conducted on the Cobas 6000 system with Roche's kit
* Serum ferritin concentrations measurement: Quantification of serum
ferritin by immunohistochemistry on the Cobas 6000 system with Roche's kit
* Diagnostic criteria:
- Stages of CKD: K/DOQI 2002 [2]:
Table 1:
- Serum hs-CRP > 5 mg/L: diagnosed as increase
* Statistical analysis: Statistical analyses were conducted using SPSS 20.0
Trang 3RESULTS
The study group with average age was 52.65 years old, there were 72.6% male; 27.4% female, mean glomerular filtration rate was 8.3 mL/min
Table 2: Iron and ferritin concentrations between study group and control group
(11.56 - 19.26)
10.7 (6.62 - 15.25) < 0.001
Iron (µmoL/L)
(68.05 - 255.22)
403.73 (211.36 - 548.42) < 0.001
Ferritin (ng/mL)
The concentrations of serum iron in study group was significantly lower than control group (10.7 µmoL/L versus 15.81 µmoL/L) with p < 0.001 The concentrations of serum ferritin in study group was higher than control group with p < 0.001 (403.73 ng/mL versus 198.45 ng/L)
Table 3: Relation between iron, ferritin concentrations and stage of CKD in study
group (n = 124)
Our results showed that serum ferritin concentrations were significantly related with the stages of CKD (p < 0.05) However, serum iron concentrations were not significantly related with the stages of CKD (p > 0.05)
Table 4: Correlation between serum iron, ferritin concentrations and serum creatinine
(n = 124)
Creatinine (µmoL/L) Indexes
Serum iron concentration was positively correlated with serum creatinine concentration (r = 0.201, p < 0.05), whereas ferritin level was not correlated with serum creatinine levels (p > 0.05)
Trang 4Chart 1: Correlation between serum iron concentration and serum creatinine Table 5: Relation between serum iron, ferritin concentrations and hs-CRP (n = 112)
(median)
Ferritin (ng/mL) (median)
(4.35 - 12.34)
431.25 (231.5 - 567.73)
(8.8 - 18.6)
385.2 (193.1 - 544.61)
In patients with elevated hs-CRP levels, serum iron concentrations were significantly lower than those without elevated hs-CRP (p < 0.001) In contrast, serum ferritin concentrations in patients who elevated hs-CRP was not significantly higher than non elevated hs-CRP group with p > 0.05
Table 6: Correlation between serum iron, ferritin concentrations and hs-CRP (n = 112)
hs-CRP (mg/L) Indexes
Correlation equation
There was no correlation between serum ferritin concentration and hs-CRP level, but there was a negative correlation between iron and hs-CRP levels (r = -0.229; p < 0.05)
Trang 5Chart 2: Correlation between serum iron concentration and hs-CRP
DISCUSSION
As the results in table 1, we found that
patients with stage 3 - 5 CKD had lower
serum iron concentrations and higher serum
ferritin concentrations than control group
Malyszko J’s study also showed that the
average concentrations of serum iron and
ferritin in chronic kidney failure was lower
than control group significantly (with p < 0.05
and 0.001, respectively) [8] Serum ferritin
is frequently used as a marker of iron
status in CKD patients Serum ferritin
concentrations results from the leakage of
tissue ferritin, an intracellular iron storage
protein shell with a molecular weight of
about 450 kDa, containing heavy (H) and
light (L) subunits Serum ferritin is slightly
different than tissue ferritin and contains
little or no iron While tissue ferritin clearly
plays a role in intracellular iron handling,
the role of serum ferritin is less clearly
understood The level of ferritin in plasma
represents the balance between its
secretion, which is directly related to
intracellular iron synthesis, and its
clearance, mainly in liver and other organs [4] However, liver dysfunction and inflammatory factors may interfere with the synthesis and clearance of ferritin, thereby increasing serum ferritin levels due
to circumstances not related to iron metabolism
Our results showed that serum ferritin concentration was significantly related to the stages of CKD We also created the correlation equation between serum iron and creatinine concentrations (iron = 0.004 x creatinine + 9.48) These results were similar to Fishbane S that among women, there was a trend toward lower decreasing mean transferrin satuation for progressively lower levels of renal function (p < 0.02), and a statistically significant trend toward increasing serum ferritin for progressively lower levels of renal function (p < 0.0001) [3] Iron is a vital element for numerous bodily functions, most notably
as an ingredient of hemoglobin Most healthy people can achieve a stable iron balance, managing to ingest the required
Trang 6amount of iron in the diet to compensate
for the small amount of daily iron loss
from the gut However, many patients
with advanced CKD are in negative iron
balance as a result of reduced dietary
intake, impaired absorption from the gut,
and increased iron losses, so serum iron
concentrations mostly decreased In
our study, it had an increasing in serum
ferritin concentrations The possible
explanation is the effect of inflammation
It is well known that occult inflammation is
commonly present in CKD and may
increase in prevalence with progressive
disease [7] Inflammation has a profound
effect on iron indices Previously, in
hemodialysis, hs-CRP, an indicator of
inflammation, was found to be highly
correlated with serum ferritin values [3]
In table 4 and 5, we found that serum
iron concentrations in patients who
elevated hs-CRP was significantly lower
than non elevated hs-CRP group, and
there was no correlation between ferritin
and hs-CRP levels Kalantar-Zadeh
K’s study also showed that there was a
positive correlation between serum ferritin
and serum hs-CRP concentrations [5]
Inflammation has been implicated in
several complications in CKD, including
malnutrition and accelerated
atherosclerosis It also blunts the iron
utilization and induces resistance to
erythropoietin therapy The exact pathway
by which the inflammatory cascade
results in erythropoietin resistance is not
completely understood It has been
hypothesized that inflammatory activators
have a pro-apoptotic effect on erythroid
progenitor cells and compete with the
anti-apoptotic effect of erythropoietin, the end result being erythropoietin resistance Serum ferritin is also an acute phase reactant, it may also be elevated during inflammation Thus an elevation of serum ferritin can be due to an increase in body iron stores or an inflammation, both of which are hazardous in patients with CKD
CONCLUSIONS
In our study, the concentrations of serum iron in study group was significantly lower than control group (p < 0.001), but the concentration of serum ferritin in study group was higher than control group with p < 0.001 Serum ferritin concentration was significantly related to the stages of CKD (p < 0.05) Iron levels were positively correlated with serum creatinine level (r = 0.201; p < 0.05) and negatively correlated with hs-CRP level (r = -0.229; p < 0.05)
REFFERENCES
1 Dignass A, Farrag K, Stein J Limitations
of serum ferritin in diagnosing iron deficiency
in inflammatory conditions J Chronic Dis
10.1155/2018/9394060 eCollection 2018
2 K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, classification,
and stratification Am J Kidney Dis, 2002, 39 (2 Suppl 1), pp.S1-266
3 Fishbane S et al Iron indices in chronic
kidney disease in National Health and Nutritional Examination Survey 1988 - 2004
Clin J Am Soc Nephrol, 2009, 4 (1), pp.57-61
4 Kalantar-Zadeh K et al Serum ferritin is
a marker of morbidity and mortality in hemodialysis patients Am J Kidney Dis 2001,
37 (3), pp.564-572
Trang 75 Kalantar-Zadeh K, R.A Rodriguez, M.H
Humphreys Association between serum
ferritin and measures of inflammation, nutrition
and iron in haemodialysis patients Nephrol
Dial Transplant 2004, 19 (1), pp.141-9
6 Krishnan A et al Anaemia of chronic
kidney disease: What We Know Now 2017,
Vol 1, p.11
7 Landray M.J et al Inflammation,
endothelial dysfunction, and platelet activation
in patients with chronic kidney disease: the chronic renal impairment in Birmingham (CRIB) study Am J Kidney Dis 2004, 43 (2), pp.244-253
8 Malyszko J et al Hepcidin, iron status,
and renal function in chronic renal failure, kidney transplantation, and hemodialysis Am
J Hematol 2006, 81 (11), pp.832-837
9 Wish J.B Assessing iron status: beyond
serum ferritin and transferrin saturation Clin J
Am Soc Nephrol 2006, 1 Suppl 1, pp.S4-S8