JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY VollO-Apr/2015
Study on concentration of iron, ferritin, transferrin and serum transferrin saturation in ciironic kidney patients undergoing hemodialysis at 108 Military Central Hospital
Nguyen Thi Thuy, Ngo Quan Vu, Tran Thanh Son, Tong Thi Thu Hang, Nguyen Van Cuong Summary
108 Military Central Hospital
Objective: Study on concentration of iron, ferritin, transferrin, level of serum transferrin saturation, and iron status of chronic kidney patients undergoing chronic hemodialysis following 2006 K/DOQl guidelines. Subject and method: Quantification of iron, ferritin, transferrin, calculation of level serum transferrin saturation and iron deficiency proportion of 70 chronic kidney patients undergoing hemodi- alysis. Result: Iron concentration was normal in 50 patients (71.4%), high m 17 patients (14.3%), and low m 3 patients (4.3%). Ferritin concentration was normal in 7 patients (10%), high in 63 patients (90%), no patient had low ferritin concentration. Transferrin concentration was normal in 6 patients (8.6%), low in 64 patients (91.4%), no patient had high transferrin concentration. TSAT was normal in 24 patients (33.4%), high in 38 patients (54.2%), low in 8 patients (11.4%). 36 patients (51%) had iron overload Con- clusion: Majority of patients had normal iron concentration but highferritin and low transferrin levels.
More than half of patients had iron overload.
Keywords: Iron concentration, ferritin, transferritin, serum transferrin saturation, chronic kidney dis- ease on hemodialysis.
1.Background
In recent years, t h e use of Erythropoeitin ther- apy (ESAs: Erythpoietin Stimulating Agents) in chronic kidney patients receiving hemodialysis (CKP HD) have been created a new breakthrough, t o re- place blood transfusion m e t h o d for treatment of blood deficiency in CKP HD. For t h e best perform- ance of ESAs therapy in t h e treatment of CKP HD patients w i t h anemia, beside the use of right dose of ESAs and specific indication, we need t o support other supplements that are related t o t h e creation of blood material such as iron, folic acid, protides, in which iron is t h e most important material. The effec- tiveness use o f ESAs therapy often depends on t h e level o f iron concentration available in t h e patient's
Correspondence to: Nguyen Thi Thuy - Department of Hemodialysis, 108 Military Central Hospital Email: thuys0401 @gmail.com
body so that the assessment of iron status in the pa- tient and the full supplement of iron is essential in the treatment of iron deficiency anemia in patients w i t h CKP HD. The incorrect assessment of iron status in patients w i t h CKP HD will result in bad outcome such as not enough iron compensation and in effec- tive treatment of anemia, or supply patient w i t h too much iron that leads t o iron overload and cause stagnant iron in t h e organs. The indirect measure- ments t o assess iron status in patients including tests of quantitative serum iron concentration, se- rum ferritin and transferrin, transferrin saturation (TSAT). These parameters are usually corresponds t o t h e level of hemoglobin in the blood, they are useful in identifying iron deficiency or iron overload, as well as in monitoring the effectiveness of iron sup- plementation in the treatment of iron deficiency anemia in patients w i t h CKP HD. In fact, w e studied the subject: "Study on concentration of iron, ferritin.
JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY Vol10-Apr/20J
transferrin and serum transferrin saturation in chron- ic kidney patients undergoing hemodialysis" w i t h t w o objectives:
1. Study o n concentration o f iron, ferritin, trans- ferrin and serum transferrin saturation in chronic kidney patients undergoing hemodialysis.
2. Evaluation of the iron status of patients w i t h chronic renal failure receiving hemodialysis as rec- o m m e n d e d by K/ DOQl 2006.
2. Subject and method 2.1. Subject
The study was conducted on 70 patients w i t h end-stage chronic renal failure treated by chronic hemodialysis at Department of Hemodialysis - 108 Military Central Hospital.
* Selection criteria for patients in the study:
- The patients were diagnosed w i t h end-stage chronic renal failure, according to Nguyen Van Xang criteria and the patients under w e n t renal replace- ment therapy by intermittent hemodialysis 12 hours/week.
* Exclusion criteria:
- The patient does not agree t o participate in t h e research.
- The patient receives enrichment of iron and iron preparations 1 week before blood sampling studies.
- Female patients in menstrual cycle during blood sampling in the study.
- Patients w i t h cancer.
- Patients w i t h acute pathological bleeding such as gastrointestinal bleeding, hemorrhoid bleeding ...
- Patients w i t h chronic renal failure due t o sys- temic diseases.
2.2. Method
This is a cross-sectional descriptive study. The patient's parameters were compared w i t h t h e refer- ence value.
* Hematology tests:
Assess the degree of anemia and anemia classi- fication, including the monitoring indicators: red
blood cell count, h e m o g l o b i n level. HematociJ mean erythrocyte v o l u m e (MEV), t h e average a m o u n t of blood p i g m e n t h e m o g l o b i n (MCH), h i m o g l o b l n concentration mean h e m o g l o b i n (MCH^
w h i t e blood cell (WBC) count, platelets.
* Tests assess iron status:
- iron Serum: Quantitative serum iron concentra^
tion by means of comparing colors. Tests were con- ducted on system of Cobas -t-6000 with Roche kit.
- Serum Ferritin: Quantification o f serum ferritin concentration by means of electrochemical lumi- nescence i m m u n e system Cobas 6000 testing ma- chine w i t h Roche kit.
- Serum transferrin: Quantification of serum transferrin concentration by t h e m e t h o d of measur- ing turbidity i m m u n e system chemicals Cobas 6000 w i t h Roche kit. Human transferrin creates agglutina- t i o n w i t h antibodies against human transferrin (ob- tained from rabbits) and generate precipitate, pre- cipitation level was mechanically measured.
- Saturation of transferrin: Transferrin saturation (TSAT- transferrin saturation) was calculated using the formula:
3.982xserumiron concentratiai (iFnoi /L)
TSAT- — , • , ,,, ^100%
Transferrin (g /L)
*Assessment of iron status based on recom- mendations of t h e report K/DOQ12006:
4- Absolute iron deficiency: Ferritin<100ng/ml andorTSAT<20%.
Functional iron deficiency: FerrltinlOO- 800ng/ml and TSAT20-50%.
+ iron Overload: Ferritin >800ng/ml and TSAT>50%
The obtained results were compared with refer- ence values provided by t h e Testing Laboratory of 108 Central Military Hospital.
*Data analysis using SPSS17.0 software to de- termine t h e mean values. Using t-student test to compare the mean values and chi square test to compare percentages, p value less t h a n 0.05 was considered statistically significant.
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3. Result
Tablel. Mean age and gender of the patients (n = 70)
Age(year) 20-30 31-40 41-50 51-60 61->70
Total Mean age
( X+SD)
Gender Male
0 9 20 25 3 57 49.85 ±7.35
50.70
Female 1 1 2 5 4 13 51.53±12.75
±8.52
Sampling time (year)
< 1 1-5 6-10 11-15
>15 Total
Patient (%) 6 (8.6) 29(41.3) 23 (33.0) 10(14.2) 2 (2.9) 701100) Mean time of sampling
5.86 ± 4.19 year
The mean age of the patients was: 50.70 + 8.52. Gender: Male accounted for 57 patients (81,4%) and 13 female patients (18.6%). The average duration of hemodialysis was: 5.86 ± 4.19 years. There were 35 patients (50%) had demodialysis duration less than 5 years and 35patients (50%) had hemodialysis duration more than 5 years.
Table 2. Characteristics of patients witli anemia
Level of blood deficiency (Hb)
Mild
Moderate Severe
Patient (%) 49 (70) 16(22.9) 05(7.1)
Blood deficiency relative to red cell morphology Anemia HC normal class identity Anemia small HC hypo chromia
Patient (%) 64 (91.4)
06 (8.6)
Anemia was mostly in moderate and mild levels, severe anemia accounted for only 7.1%
Most anemia patients were class identity and there were only few patients with anemia hypo chromia.
Table 3. Concentration of iron, ferritin, transferrin saturation and serum transferrin of the patients
In value reference Increase compare to val-
Decrease compare to val-
Iron (pmol/L) 6.6 - 28.0 20.56 + 10.03
50 patients (71.4%) 17 patients
(24.3%) 3 patients
(4.3%)
Ferritin (ng/ml) 13 - 400 1180.34 ±639.39
7 patients (10%) 63 patients
(90%) 0 patients
(0%)
Transferrin (g/L) 2,0 - 3,6 1.54 + 0.33 6 patients (8.6%) 0 patients
(0%) 64 patients
(91.4)
TSAT (%) 2 0 - 5 0 55.62 + 28.31
24 patients (34.4%) 38 patients
(54.2%) 8 patients
(11.4%)
, .
The majority of patients had serum iron levels in the normal range. No patients had low serum ferritin levels, whereas 90% of patients had high ferritin levels when compared with the reference value.
No patients had high serum Tranferrin concentrations, but 91.4% of patients had low concentrations of
transferring when compared with reference values.
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Table 4 . Evaluation of iron status of the patient group as recommended b y K/DOQI2006 Status
Absolute Iron deficiency Functional iron deficiency Overload iron
Total
Numbers of patients 10 24 36 70
Percentage (%)
14.3 1 34.3
51.4 100
1 i
i I
There were more than half of patients presenting status of iron overload.
Table 5. Comparison of the average value of concentrations of serum iron, ferritin, transferring and TSAT in dialysis patient groups with <,S years and >5 years
Serum iron (|jmol/L}
Ferritin(ng/ml) Transferrin (g/L) TSAT (%)
Patient with dialysis £ 5 years (n=35}
16.2419.50 918.76 ±514.90
1.61 ± 0.37 41.92 ± 25.66
Patient with dialysis
> 5 years (n= 35) 24.88 ± 8.86 1441.92 ±650.91
1.47 ±0.28 69.33 ±24.10
P
<0.05
<0.05
>0.05
<D.05
The average value of concentrations of serum iron, ferritin and TSAT of patients with dialysis >5 years were statistically significantly higher than that of patients with dialysis sSyears with p<0.05. The average value of transferring concentration of patients with dialysis>5 years was lower than that of patients with di- alysis < Syears, but the difference was not statistically significant with p>0.05.
Table 6. Evaluation of iron status of dialysis patients <5yearsand >5yearsas recommended by K/DOQI2006
status Absolute iron deficiency Functional iron deficiency Overload iron
Total
Dialysis patient < 5 years Patient (nl
9 16 10 35
%
25.7 45.7 28.6 100
Dialysis patient> 5 years Patient (n)
1 8 26 35
%
2.8 22.8 74.4 100
P
<0.05
<0.05
<0.05
In the patients with dialysis< 5 years, the rates of absolute iron deficiency and functional iron defi- ciency were significantly higher than that in the pa- tients with dialysis> 5 years with p<0.05. In contrast, the rate of iron overload in patients with dialysis> 5 years was significantly higher than that in patients with dialysis < 5 years with p<0.05.
4. Discussion
In our study, 100% was anemic patients, mostly mild and moderate anemia (Hb indicator) with the rate of 70%) and 22.9% respectively, and only 7.1%
severe anemia. This is consistent with research re-
sults of other Vietnamese authors in patients with
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CKD HD. According t o Vo Tam and Ngo Thuy Trang w h o did t h e study o n 65 patients w i t h CKD HD w i t h w i d e range o f stages (Hue hospital-2008) [1], t h e prevalence of moderate and severe anemia ac- counted for 70.81%, and t h e results was different from our results, w h i c h may be due t o t h e patients, w h o were n o t involved in dialysis cycle, t h e treat- m e n t of anemia was n o t closely m o n i t o r e d , none specific regimen ... e.g. group o f patients w h o were in dialysis cycle treatment. A m o n g 70 patients o f our study, t h e number of patients achieving Hb 110 g/L - 120 g/L as recommended by t h e KDOQl 2006 was 19 patients, accounting for 27.1 % [3].
The average concentration of serum iron in pa- tient group was 20.56 ± 10.03 p m o l / L w i t h i n nor- mal limits, w h i c h was also suitable for t h e character- istics of t h e anemia patients w i t h CKD HD, mostly were class identity. Serum iron did not show t h e iron accumulation in t h e body, iron was transported in the blood plasma as well as t h e a m o u n t o f iron pre- sented in t h e environment hematopoiesis in bone marrow. So w e could not rely on serum iron concen- tration t o assess whether patients w i t h iron defi- ciency or iron accumulation could satisfy t h e needs of t h e bone marrow. However, concentration of se- rum iron was meaningful for us t o calculate transfer- rin saturation level and determine t h e absolute or relative deficiency o f iron or iron overload ...
The concentration of average serum ferritin in the g r o u p of patients was 1180.34 ± 639.39 n g / m l much higher t h a n normal values (13-400 ng/ml). The decreasing o f Ferritin levels was relative t o iron ac- cumulation in t h e body decreases. In our study, as well as other authors such as Tran Thi Thuan [2] t h e Ferritin concentrations was higher t h a n t h e refer- ence value and higher t h a n in the study of other au- thors in t h e w o r i d . The cause of this increase was d u e t o t h e previously treated patients w i t h anemia caused by repeated blood transfusions that caused accumulation o f iron in t h e body, increased ferritin, and resulted in iron overloading.
Tranferrin concentrations of t h e patients in t h e study decreased compared t o the reference in 64 patients (91.4%), there were only 6 patients w i t h
transferrin levels in t h e normal range, accounting for 8.6%. No patient had transferrin concentrations higher than t h e reference in our study, as well as in studies of other authors such as Tran Thi Thuan [2].
Since transferrin was a parameter that was used t o calculate t h e TSAT, the study or survey index trans- ferrin often associated w i t h TSAT value.
The average value of TSAT in patients was 55.62 ± 28.31%. When compared w i t h t h e reference values, there were 8 patients w i t h low TSAT (11.4%), 38 pa- tients w i t h high TSAT (54.2%) and 24 patients had normal TSAT (34.4%). In contrast t o iron deficiency, the problem of iron overload in patients w i t h CKD HD was reported by many authors, particularly in patients w h o received iron supplementation but did not control iron status and in blood transfusion pa- tients. Therefore, careful assessment of iron status is very important in patients w i t h CKD HD before and during treatment o f anemia using EPO to enhance iron correctly, ovoid iron deficiency or iron overload for patients. As recommended by the K/DOQI w h e n serum ferritin> 8 0 0 n g / m l and TSAT> 50% will pro- duce signs of iron overload, in this case w e should use supplements to excrete iron and stop using iron w i t h i n 3 months.
When assessed iron status of t h e patients in our study as recommended by the KDOQl 2006, there were 51.4%of patients (n ^ 36) w i t h iron overload, 34.4% (n = 24) w i t h iron deficiency function and only 14.3% (n = 10) w i t h lack of absolute iron. We know that there were a significant percentage of e n d - stage CKD HD patients w i t h iron overload, t h e cause may be due to the use of iron w i t h o u t t h e assess- m e n t of iron status, or due t o repeated blood trans- fusions many times.
With the recommendations of t h e K/DOQl, if the CKD HD patients had absolute iron deficiency, they should be supplemented intravenous iron lOOOmg/month for 2 months then reassess ferritin and TSAT indicators in order to know whether it is needed t o receive further treatment.
Evaluation of the iron status of patients in t w o groups; < 5 years of dialysis and > 5 years of dialysis as recommended by K/DOQl: In t h e patients < 5
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years of dialysis g r o u p , t h e rate of patients lacking absolute iron and anemia function was statistically significantly much higher t h a n that in the patients >
5 years of dialysis g r o u p , w i t h p<0.05. This result was similar t o that of authors Kalantar Zadeh (2001) [4].
Conversely, t h e rate of iron overioad in t h e patients w i t h dialysis> 5 years g r o u p was statistically signifi- cantly higher than t h a t in t h e patients w i t h dialysis <
5 years group, w i t h p<0.05. The reason that t h e long-term dialysis patients had high iron overioad because in t h e previous year w h e n the ESAS has not been widely used, t h e blood transfusion was t h e main therapy for t h e treatment of anemia in patients w i t h CKD HD, prolonged and repeated blood trans- fusions many times led to accumulation o f large a m o u n t of iron in t h e body, and this unexcreted a m o u n t could cause accumulation of iron in t h e fis- sue o f various organs. In our department, t h e new ESAS therapy had been applying since 2009. Iron overload is a cause of t h e increase in cardiovascular diseases, cancer, inflammation in patients w i t h CKD HD, so that iron supplementation should be closely monitored w i t h t h e Iron and hematologic status in t h e body. According t o Masashi Suzuki (Japan-2003) [5] when the hematocrit level was not responding t o ESAS therapy, serum ferritin concentration increased and exceeded 500 n g / m l , we need t o stop iron treatment.
patients w i t h > 5 years dialysis g r o u p had signHf cantly higher rate of iron overioad t h a n that of p tients w i t h & 5 years dialysis g r o u p .
References
1. Vo Tam, Ngo Thijy Trang (2008) Nghiin cUu tM hinh vo dgc diem thieu mdu d binh nhan suy thdn man tgi binh viin trung uang Hue. Tap chi Y hoc thiic hanh (618-F 619), so 9: tr. 21 - 24.
2. TranThjThuan (2010) Nghiinciiusi/thayd6in6ng d& sat, ferritin huyet thanh d benh nhan suy than man tinh giai doan III- IV. Luan van cao hoc Npi khoa HVQY.
3. K/DOQl (2006) Clinical practice guidelines andCHnicsl practice recommendation for anemia in chronic kidney disease. Am J KidneyZto 50(3): 471-530.
4. Kalantar Zadeh K, Don BR, Rodriguez RA, Hum- phreys MH (2010) Serum ferritin is a marker of mor- bidity and mortality in hemodialysis patients. Am J Kidney Dis. Mar 37 (3): 564-572.
5. iVIasashi Suzuki, Yoshikatu Kaneko (2003) Transfer- rin saturation versus reticulocyte hemoglobin con- tent for iron deficiency in Japanese hemodialysis pa- tients. Kidney International Journal Vo! 63.
5. Conclusion
Study on concentration of iron, ferritin, transfer- ring saturation and serum transferring in70 pafients w i t h CKD HD, w e have some comments as follow:
- Serum iron levels in t h e normal range found in 71.4% o f patients. Up t o 90% of t h e patients had blood ferritin concentrations higher than the refer- ence value. 91.4%) of patients had lower transferring concentration than reference value. Tranferrin satu- ration increased in 54.2%), in normal range in 34.4%
and decreased in 11.4% of patients.
- Of t h e 70 patients, there were14.3% patients w i t h absolute iron deficiency, 34.4%i w i t h iron defi- ciency and 51.4%) w i t h functional iron overload. The
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