45-1386169192

download 45-1386169192

of 9

Transcript of 45-1386169192

  • 8/12/2019 45-1386169192

    1/9

    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 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 (

  • 8/12/2019 45-1386169192

    2/9

  • 8/12/2019 45-1386169192

    3/9

    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 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

  • 8/12/2019 45-1386169192

    4/9

    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 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

  • 8/12/2019 45-1386169192

    5/9

    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 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

  • 8/12/2019 45-1386169192

    7/9

  • 8/12/2019 45-1386169192

    8/9

    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 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

  • 8/12/2019 45-1386169192

    9/9

    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 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