Objectives: To evaluate the serum iron and ferritin oncentrations in patients with chronic kidney disease (CKD) predialysis and its relation with stages of CKD and some other features. Subjects and methods: A cross-sectional study on a group of 175 patients with CKD stage 3 - 5 and a control group of 51 healthy people at Department of Nephrology and Hemodialysis, 103 Military Hospital.
Trang 1SURVEY OF SERUM IRON AND FERRITIN CONCENTRATIONS
IN PATIENTS WITH STAGE 3 TO 5 CHRONIC KIDNEY DISEASE
Nguyen Van Hung*; Nguyen Cao Luan**; Le Viet Thang***
SUMMARY
Objectives: To evaluate the serum iron and ferritin concentrations in patients with chronic kidney disease (CKD) predialysis and its relation with stages of CKD and some other features Subjects and methods: A cross-sectional study on a group of 175 patients with CKD stage 3 - 5 and a control group of 51 healthy people at Department of Nephrology and Hemodialysis,
103 Military Hospital Results: The average concentrations of serum iron in study group was significantly lower than control group (12.87 ± 6.85 µmol/L versus 16.57 ± 5.83 µmol/L), but the average concentrations of serum ferritin in study group was higher than in the control group (308.59 ± 178.41 ng/mL versus 159.89 ± 87.98 ng/mL) with p < 0.01 Serum iron and ferritin concentrations were significantly associated with the stages of CKD (p < 0.05) Ferritin levels were positively correlated with serum creatinine levels (r = 0.256; p < 0.01) and hs-CRP levels (r = 0.383; p < 0.001) Conclusion: Patients with stage 3 - 5 CKD, predialysis had lower serum iron and higher serum ferritin concentrations compared to control group There was significant correlation between serum iron, ferritin with serum creatinine concentrations and hs-CRP levels
* Keywords: Chronic kidney disease; Serum iron; Serum ferritin; Predialysis.
INTRODUCTION
Chronic kidney disease is a worldwide
public health problem with an increasing
incidence and prevalence, poor outcomes
and high cost Chronic kidney disease
causes not only kidney failure but also
complications of decreased kidney function
and cardiovascular disease [5]
Anaemia of chronic kidney disease (CKD)
is widely common in patients with renal
impairment and is associated with significant
morbidity and mortality 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 successfully by recombinant human EPO 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 [4] Absolute iron deficiency, the iron deficiency that is characterized by low orabsent bone marrow staining for iron,
is to be distinguished from functional or
* Transport Hospital
** Bachmai Hospital
** 103 Military Hospital
Corresponding author: Nguyen Van Hung (hunggttw@gmail.com)
Date received: 04/10/2017
Date accepted: 22/11/2017
Trang 2relative iron deficiency, which is defined
as a response to intravenous iron with an
increase in hemoglobin (Hb) or a decrease
in erythropoiesis-stimulating agent (ESA)
requirement [8] Therefore, we conducted
this research aiming: To assess the
serum iron and ferritin concentrations in
patients with stage 3 - 5 CKD and its
relation with stages of CKD, serum creatinine
concentrations and hs-CRP
SUBJECTS AND METHODS
1 Subjects
The study was conducted on a group
of 175 patients with CKD stage 3 - 5,
predialysis and a control group of 51 healthy
people at Department of Nephrology and
Hemodialysis, 103 Military Hospital
* Excluding criteria: Blood transfusion,
acute bleeding, some acute diseases,
being performed 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+ combined with ferrozine buffers to form a color complex After that, the test is conducted
on the Cobas 6,000 system with Roche's kit
- Serum ferritin concentrations measurement: Quantification of serum ferritin by immunohistochemistry on the Cobas 6,000 system with Roche's kit
* Diagnostic criteria:
Table 1: Stages of CKD: K/DOQI 2002 [1]
- Serum hs-CRP > 5 mg/L: diagnosed as increase
* Statistical analysis:
Statistical analyses were conducted using SPSS 20.0
Trang 3RESULTS AND DISCUSSION
The study group with an average age of 53.26 years old, 69.1% male, 30.9% female There was not significant difference compared to those of control group
Table 2: Iron and ferritin concentrations between study group and control group
Iron* (µmoL/L)
Ferritin* (ng/mL)
In our study, the average concentrations
of serum iron in study group was significant
lower than control group (12.87 µmol/L
versus 16.57 µmol/L) with p < 0.01 The
average concentrations of serum ferritin in
study group was higher than in the control
group with p < 0.01 (308.59 ng/mL versus
159.89 ng/mL) The study by Malyszko J
also showed that the average concentrations
of serum iron and ferritin in chronic kidney
failure was significantly lower than control
group (with p < 0.05 and 0.001, respectively)
[7] Serum ferritin is a frequently used
marker of iron status in CKD patients
Serum ferritin concentration 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 [3] However, liver dysfunction and inflammatory factors may interfere with the synthesis and clearance of ferritin, thereby increasing serum ferritin levels due to circumstances unrelated to iron metabolism
Trang 4Table 3: Relationship between iron, ferritin concentrations and stages of CKD in study
group (n = 175)
Our results showed that serum iron and ferritin concentrations were significantly associated with the stages of CKD (p < 0.01) Patients with stage 3 CKD had the highest levels of serum iron and the lowest levels of serum ferritin, while the patients with stage 5 CKD had the lowest iron concentrations and the highest serum ferritin concentrations
Table 4: Correlation between serum iron, ferritin concentrations and serum creatinine
(n = 175)
Indexes
Creatinine (µmol/l)
Correlation equation
Serum iron concentrations was not
correlated with serum creatinine
concentrations, whereas ferritin levels
were positively correlated with serum
creatinine levels (r = 0.256; p < 0.01) Our
results in table 3 and 4 showed that
serum iron and ferritin concentrations
were significantly associated with the
stage of CKD as well as the serum
creatinine concentration These results
were similar to those by Fishbane S’
(the same subjects): among women, there
was a trend toward lower decreasing
mean TSAT 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) [2] Iron is a vital element for numerous body functions, most notably as an ingredient of hemoglobin (Hb) Most healthy people can achieve a stable iron balance, managing to ingest the required amount of iron in the diet
to compensate for the small amount of daily loss iron 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 loss iron, so serum iron concentrations mostly decreased In our study, there was an increase in serum ferritin
Trang 5concentrations It is likely due to the
effect of inflammation It is well known
that occult inflammation is commonly
present in CKD and may increase with
progressive disease [6] 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 [2]
Ferritin = 0.121xCreatinine + 240.46
0
100
200
300
400
500
600
700
800
Creatinine
Chart 1: Correlation between serum ferritin concentration and serum creatinine
Table 5: Relationship between serum iron, ferritin concentrations and hs-CRP
(n = 175)
In patients with elevated hs-CRP levels, serum iron concentrations were significantly lower than those without elevated hs-CRP, but the difference was not statistically significant (p > 0.05) By contrast, serum ferritin concentrations in patients who elevated hs-CRP was significantly higher than non elevated hs-CRP group with p < 0.001
Trang 6Table 6: Correlation between serum iron, ferritin concentrations and hs-CRP (n = 175)
Indexes
hs-CRP (mg/l)
Correlation equation
There was no correlation between serum iron concentrations and hs-CRP levels, but there was a positive correlation between ferritin and hs-CRP levels (r = 0.383; p < 0.001)
Ferritin = 0.121xCreatinine + 240.46
0 100
200
300
400
500
600
700
800
Chart 2: Correlation between serum ferritin concentration and hs-CRP
In table 5 and 6, we found that serum
ferritin concentration in patients who elevated
hs-CRP was significantly higher than non
elevated hs-CRP group and there was a
positive correlation between ferritin and
hs-CRP levels The study by
Kalantar-Zadeh K also showed that there was a
possitive correlation between serum ferritin
and serum hs-CRP concentration (r = 0.31;
p = 0.005) [4] 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 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 which may
Trang 7also be elevated during an 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 average concentration
of serum iron in study group was significantly
lower than that in the control group (12.87 ±
6.85 µmol/L versus 16.57 ± 5.83 µmol/L),
but the average concentration of serum
ferritin in study group was higher than that in
the control group (308.59 ± 178.41 ng/mL
versus 159.89 ± 87.98 ng/mL) with p < 0.01
Serum iron and ferritin concentrations were
significantly associated with the stages of
CKD (p < 0.01) Ferritin levels were positively
correlated with serum creatinine levels
(r = 0.256; p < 0.01) and hs-CRP levels
(r = 0.383; p < 0.001)
REFFERENCES
1 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
2 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
3 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
4 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.141-149
5 Krishnan A et al Anaemia of chronic
kidney disease: What We Know Now 2017, Vol 1, 11
6 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
7 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
8 Wish J.B Assessing iron status: beyond
serum ferritin and transferrin saturation Clin J
Am Soc Nephrol 2006, 1, Suppl 1, pp.S4-S8