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Vidyashankar P. et. al.DIAGNOSIS OF IRON DEFICIENCY OF CHRONIC KIDNEY DISEASE : VALIDITY OF IRONPARAMETERS, RETICULOCYTE HEMOGLOBIN CONTENT(CHR) AND HYPOCHROMIC RED CELLS
IN INFLAMMATORY STATE
Int J Cur Res Rev, Nov 2013/ Vol 05 (21)
Page 83
IJCRRVol 05 issue 21
Section: Healthcare
Category: Research
Received on: 17/09/13
Revised on: 12/10/13
Accepted on: 14/11/13
DIAGNOSIS OF IRON DEFICIENCY OF CHRONIC KIDNEY
DISEASE : VALIDITY OF IRON PARAMETERS,
RETICULOCYTE HEMOGLOBIN CONTENT(CHR) AND
HYPOCHROMIC RED CELLS IN INFLAMMATORY STATE
Vidyashankar P.1, Alan F. Almeida2, Niwruti K. Hase3, Arun Halankar3,Harinakshi Rai3, Sadanand Bhusari4
1Department of Nephrology, Rajarajeshwari Medical College Hospital and research
Institute, Kambipura, Mysore Road, Bangalore, KA, India2Chief of the Division of Nephrology, PD Hinduja Hospital, Mumbai, MH, India3Department of Nephrology, Seth GS Medical College and K.E.M Hospital, Parel,
Mumbai, India4Consultant Nephrologist, Akola, Maharashtra, India
E-mail of Corresponding Author: [email protected]
ABSTRACT
Introduction: Diagnosis of iron deficiency is difficult in presence of uraemia. The validity of these
tests in the presence of inflammation has not been studied, and it formed the basis of this enquiry.
Methods: On hundred and twenty two consecutive chronic kidney disease (CKD III, IV, V-non
dialysis) patients were enrolled. Complete hemogram, iron studies, Reticulocyte hemoglobin content
(CHr) and percent hypochromic red cells (%Hypo), high sensitive CRP (hs-CRP) levels were done. In
the study group of 122 patients screened, 103 patients were found to be iron deficient by Kidney
Dialysis Outcome Quality Initiative (KDOQI) criteria. In the iron deficient patients, intra venous iron
(i.v iron sucrose 1000mg) was administered in divided doses followed by erythropoetin and the tests
were repeated after 4 weeks of completing i.v iron therapy. If the rise in Hb> 1gm%, at the end of 4
weeks, the patient were grouped into responders (iron deficient subjects). The rest were grouped as non
responders(Iron replete).The value of the tests, individually or in combination, was determined in the
subgroups and categorized based on hs-CRP levels (
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Vidyashankar P. et. al.DIAGNOSIS OF IRON DEFICIENCY OF CHRONIC KIDNEY DISEASE : VALIDITY OF IRONPARAMETERS, RETICULOCYTE HEMOGLOBIN CONTENT(CHR) AND HYPOCHROMIC RED CELLS
IN INFLAMMATORY STATE
Int J Cur Res Rev, Nov 2013/ Vol 05 (21)
Page 85
within 3 hrs of collection. The reticulocyte
parametres like CHr absolute reticulocyte
count, reticulocyte percentage was processed
by ADVIA 120 automated hematology analyzer
(Bayers diagnostics) at Ranbaxy research
laboratory [37, 42]. The reticulocytes were
stained with RNA stain oxazine 750 and
analyzed by flow cytometric principle with
proper standardization. Serum ferritin was
tested by Enzyme Linked Iimmuno Sorbant
Assay technique, iron studies done by
colorimetric methods using SESOMEM
analyzer. C - Reactive Protein was be measured
by immunonephelometric method at the
Immunology laboratory department of
pathology. Blood urea nitrogen, serumcreatinine, serum electrolytes, urine
examination, urine culture, liver function tests,
viral markers were done at hospital central
clinical laboratory.
Statistical analysis
Statistical analysis was performed using the
computer software package of social science
(SPSS 13.1, 2005: SPSS Inc, IL, USA.) The
data was expressed as mean Standard
Deviation. Comparison of data for responders
and non responders were performed by using
the t-test or Mann-Whitney U-test as
applicable. The inter group comparison was
made by analysis of variance test (ANOVA).
The sensitivity and specificity, positive and
negative predictive values were calculated
using appropriate formula. A p value of less
0.05 was considered as statistically significant.
RESULTS
There were 64 males with mean age of
A total of 103 patients were iron-deficient by
KDOQI criteria (TSAT < 20% or Serum ferritin
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Vidyashankar P. et. al.DIAGNOSIS OF IRON DEFICIENCY OF CHRONIC KIDNEY DISEASE : VALIDITY OF IRONPARAMETERS, RETICULOCYTE HEMOGLOBIN CONTENT(CHR) AND HYPOCHROMIC RED CELLS
IN INFLAMMATORY STATE
Int J Cur Res Rev, Nov 2013/ Vol 05 (21)
Page 86
inflammation has not been evaluated . In similar
studies by Tessitoire et al[50], in non dialyzed
patients, the sensitive of CHr varied from 58.67%
to 84.5% and specificity of 78.88 to
88.67%.Validity of theses tests in the presence of
inflammation has not been evaluated .
In Hemodialysis patients, a study by Chuang CL
et al, had diagnostic sensitivity and specificity of
ferritin < 100ng/ml and TSAT < 19 % of 68.6 %
and 60.8 % respectively [44]. The efficiency of
both tests when used in combination was 64.0
%.When only ferritin
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Vidyashankar P. et. al.DIAGNOSIS OF IRON DEFICIENCY OF CHRONIC KIDNEY DISEASE : VALIDITY OF IRONPARAMETERS, RETICULOCYTE HEMOGLOBIN CONTENT(CHR) AND HYPOCHROMIC RED CELLS
IN INFLAMMATORY STATE
Int J Cur Res Rev, Nov 2013/ Vol 05 (21)
Page 87
5. Navarro JF,Macia ML. Hypochromic red cellsas an indicator of iron deficiency. J Rhematol;
24:804-805,1997
6. Wittie DL: Can serum ferritin be effectivelyinterpreted in the presence of acute phase
response? Clin Chem; 37:484-485,1991
7. Dennison HA. Limitation of serum ferritin asa marker of anemia in end stage renal Disease.
ANNA J; 26: 409-414,1999
8. New European Best Practice for the guidelineof anemia of chronic kidney disease. Nephrol
Dial Transplantation.20 (7): 1512-1587,2005.
9. Clinical practice guideline for management ofanemia of chronic kidney disease. K/DOQI
update 2006,Am J kid disease 47:855-924,
2006.10.Gokal R,Millard PR, Weatherall DJ, Callender
ST et al. Iron metabolism in hemodialysis
patients. QJ med; 48:369-391,1979
11.Konijn AM, Hershko C.Ferritin synthesis ininflammation: pathogenesis of impaired iron
release. Br J Hematol; 37:7-16,1977
12.Lipschitz DA,Cook JD,Finch CA;A clinicalevaluation of serum ferritin as an index of iron
stores.New Eng J Med 290;1213-1216,1974
13.Finch CA,Bellotti V,Stray S , Lipschitz DA:Plasma ferritin determination as a diagnostic
tool .West Ind J Med 145:657-663,1986
14.Kalantar-Zadeh K, Hoffken B, Wunsch H,Fink H, Kleiner M, Luft FC: Diagnosis of iron
deficiency anemia in renal failure patients
during the post-erythropoietin era. Am J
Kidney Dis26:292299,1995
15.Rosenberg ME: Role of transferrinmeasurement in monitoring iron status during
recombinant erythropoeitin therapy. Dial
Transplant 21:81-90,199216.Hastika J, Lasserre JJ, Schwatzbeck A, Rieter
A, Hehlmann R. Laboratory tests of iron
status. Clin Chem., 42:7:712-724. 1996.
17.Macdougall IC,Berner CM,Wild BJ,Cavil I etal. Measurement of red cell hypochromasia is
a useful indicator of iron status in renal
patients. J Am Soc Nephrol; 3:427,1992
18.Fishbane S, Galgano C, Langley RC Jr,Canfield W, Maesaka JK. Reticulocyte
hemoglobin content in the evaluation of iron
status of hemodialysis patients. Kidney Int;
52: 217-22. 1997
19.Mittman N, Sreedhara R, Mushnick R,Chattopadhyay J, Zelmanovic D, Vaseghi M,
Avram MM. Reticulocyte hemoglobin
content predicts functional iron deficiency in
hemodialysis patients receiving rHuEPO. Am
J Kidney Dis; 30: 912-22. 1997
20.Cullen P, Soffker J, Hopfl M, Bremer C,Schlaghecken R, Mehrens T, Assmann G,
Schaefer RM. Hypochromic red cells and
reticulocyte haemoglobin content as markers
of iron-deficient erythropoiesis in patientsundergoing chronic haemodialysis. Nephrol
Dial Transplant; 14: 659-65. 1999
21.Mast AE, Blinder MA, Lu Q, Flax S, DietzenDJ. Clinical utility of the reticulocyte
hemoglobin content in the diagnosis of iron
deficiency. Blood; 99: 1489-91.2002
22.Fishbane S, Shapiro W, Dutka P, ValenzuelaOF, Faubert J. A randomized trial of iron
deficiency testing strategies in hemodialysis
patients. Kidney Int; 60: 2406-. 2001
23.Y. Fukui, S. Samma , K. Fujimoto , A.Yamaguchi , Y. Umeki , M. Ooto, M. Arima
Reticulocyte hemoglobin content as a marker
of iron status in patients receiving
maintenance hemodialysis.J Nephrol ;23:123-
135. 2003
24.Brugnara C, Chambers LA.MalynnE,Goldberg MA et al. Red blood cell
regeneration induced by subcutaneous
recombinant erythropoeitin; Iron deficient
erythropoeisis in iron repletesubjects.Blood;81:956-964,1993
25.Mittman N, Sreedhara R, Mushnick R,Chattopadhyay J et al. Reticulocyte
hemoglobin content predicts functional iron
deficiency in hemodialysis patients receiving
erythropoeitin. AM J Kidney Dis; 30:912-
922,1997
-
8/12/2019 45-1386169192
6/9
Vidyashankar P. et. al.DIAGNOSIS OF IRON DEFICIENCY OF CHRONIC KIDNEY DISEASE : VALIDITY OF IRONPARAMETERS, RETICULOCYTE HEMOGLOBIN CONTENT(CHR) AND HYPOCHROMIC RED CELLS
IN INFLAMMATORY STATE
Int J Cur Res Rev, Nov 2013/ Vol 05 (21)
Page 88
26.Brugnara C, Iron deficiency anderythropoeisis .New diagnostic approaches.
Clin Chem 49; 1573-1578,2003
27.National kidney Foundation .K/DOQI Clinicalpractice guideline for anemia of chronic
kidney disease, Am J Kidney dis; 37:S182-
S238, 2001
28.Yoshikatsu Kaneko, ShigeruMiyazaki,Yoshihri Hirasawa, Fumitake G et
al, Transferrin saturation verses reticulocyte
hemoglobin content for iron deficiency in
Japanese hemodialysis patients. Kidney Int,
63:1086-1093,2003
29.Fishbane S,Galgano C,Langley RC,CanfieldW,Mawsaka JK. Reticulocte hemoglobin
content in the evaluation of iron status ofhemodialysis patients. Kidney Int; 52:217-
222,1997
30.Brugnara C,Collela GM, Cremins J, LanmgleyRC; Effects of subcutaneous recombinant
erythropoeitin in normal subjects.
Development of decreased reticulocyte
hemoglobin content and iron deficiency
erythropoeisis. J lab Clin Med 123:660-
667,1994
31.Brugnara C,Hipp MJ, Irving PJ, Lathrop H,Lee PA, Minchello EM et al:Automated
reticulocyte counting and measurement of
reticulocyte cellular indices. Am J Clin Pathol
102:602-632,1994
32.Macdougall IC, Caill I, Hulme B, and Bain Bet al: Detection of functional iron deficiency
during EPO treatment new approach. Br Men
J 304:225-226,1992
33.Schaefer RM, Schaefer L: The hypochromicred cells: A new parameter fro monitoring of
iron supplementation during EPO therapy .JPerinat Med 23:83-88,1995
34.Ali MA, Luxtan AW, Walker WHC, Serumferritin concentration and bone marrow iron
studies: a prospective study. Can Med Assoc
J; 118:945-946,1978
35.Bhandari S, Norfolk D, Brown john A, TurneyJ. Evaluation of RBC ferritin and reticulocyte
measurements in monitoring response to
intravenous iron therapy .Am J Kidney Dis;
30:814-821,1997
36.Mittman N, Sreedhara R, Mushnik R, et al,Reticulocyte hemoglobin content predicts
functional deficiency in hemodialysis patients
receiving EPO. Am J Kidney Dis; 30:912-
922,1997
37.Brugnara C, Zurakowski D, DiCanzio J, BoydT,Platt O. Reticulocyte hemoglobin content in
the diagnosis of iron deficiency in children
.JAMA:281:2225-2230,1999
38.Brugnara C,Laufer MR, Freidmann AJ,Bridges K, Platt O. Reticulocyte hemoglobin
content (CHr):early indicator of iron
deficiency and response totherapy,Blood;83:3100-2101,1994
39.Tsuchiya K,Saito M,Okano Sugiyama H,NiheiH et al .Monitoring the content of reticulocyte
hemoglobin content (CHr) as the progression
of anemia in nondialysis CKD patients. Ren
Fail; 27; 1:59-65,2005
40.Hasegawa M, Kamawara N, Koide S, MuraseM et al. Evaluation of reticulocyte hemoglobin
content, percentage of hypochronic re blood
cells, and ratio of serum ferritin receptor level
as a marker of iron deficiency erythropoeisis
in patients undergoing hemodialysis. Nephrol
Dial Transplant;14;659-665,1999
41.Mast AE, Blinder MA, Lu Q, Flax S, DietzenDJ.Clinical utility of the reticulocyte in the
diagnosis of iron deficiency. Blood; 99:1489-
91,2002
42.Kotisaari S, Romppanen J, Penttila I,Punnonen K.The ADVIA 120 hematology
analyzer;red blood cells and reticulocyte
indices are useful in the diagnosis of irondeficiency anemia. Euro J Hematology;
68:150-156,2002
43.Thomas C, Thomas L. Biochemical markersand hematological indices in the diagnosis of
functional iron deficiency. Clin Chem.;
48:1066-1076,2002
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Vidyashankar P. et. al.DIAGNOSIS OF IRON DEFICIENCY OF CHRONIC KIDNEY DISEASE : VALIDITY OF IRONPARAMETERS, RETICULOCYTE HEMOGLOBIN CONTENT(CHR) AND HYPOCHROMIC RED CELLS
IN INFLAMMATORY STATE
Int J Cur Res Rev, Nov 2013/ Vol 05 (21)
Page 90
Table 2: Comparing Mean SD of parameters in ANOVA (Analysis of variance )
Parameter Iron replete
Iron deficient
VARIABLES
CRP
>5 mgL
CRP
5 mg/L
CRP
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Vidyashankar P. et. al.DIAGNOSIS OF IRON DEFICIENCY OF CHRONIC KIDNEY DISEASE : VALIDITY OF IRONPARAMETERS, RETICULOCYTE HEMOGLOBIN CONTENT(CHR) AND HYPOCHROMIC RED CELLS
IN INFLAMMATORY STATE
Int J Cur Res Rev, Nov 2013/ Vol 05 (21)
Page 91
Table 3 : Sensitivity ,specificity of chosen cut off values of various parameters in the absence of
inflammation and presence of inflammation
Test criteria Sensitivity (%) Specificity (%)
Positive
predictivevalue (%)
Negative Predictive
Value (%)
CRP mg/L CRP mg/L CRP mg/L CRP mg/L
BASE LINE
5 5 5 5
S ferritin