Anaemia; Haemodialysis; Iron monitoring; Mature erythrocyte parameters; Percentage of hypochromic red blood cells
Abstract :
[en] Background. The percentage of hypochromic red blood cells (RBCs) (%HYPO) has been demonstrated as the best predictor of response to iron loading in haemodialysis patients treated with recombinant human erythropoietin (rHuEPO). However, we have previously shown that this parameter is positively influenced by erythropoietic activity since reticulocytes are considered hypochromic by cell counters. New cell counters are able to determine cell volume and haemoglobin (Hb) concentration separately on reticulocytes and mature erythrocytes. The aim of this study was to assess the sensitivity and specificity of mature erythrocyte parameters in detecting functional iron deficiency (FID).
Methods. A total of 32 stable chronic haemodialysis patients in the maintenance phase of rHuEPO therapy were included. Classical parameters of iron monitoring and mature erythrocyte parameters were measured after a 4-week iron-free period. Patients were classified as responders (R) or non-responders (NR) to an iron load of 100 mg iron sucrose at each dialysis session for 4 weeks, according to whether their Hb increased by >1 g/dl at the end of iron loading.
Results. Twelve patients were identified as responders. Receiver operating characteristic (ROC) curve analysis demonstrated %HYPO and its corresponding parameter on mature erythrocyte, %HYPOm, as the best predictors of FID. The other parameters were ordered as follows: tranferrin saturation (TSAT), ferritin (FRT), mature RBC Hb content (CHm), mean corpuscular Hb concentration (MCHC), percentage of mature erythrocytes with a low CHm (%lowCHm), mean content in Hb (MCH) and reticulocyte Hb content CHr. Comparing the parameters at different cut-offs, the best sensitivity, specificity and efficiency were demonstrated for HYPOm>6%.
Conclusion. The best efficiency to predict FID was found for %HYPOm>6%. The predictive value of %HYPO was quite similar. The clinical impact of %HYPOm in iron monitoring should also be tested in the induction phase of rHuEPO treatment because of its independence from erythropoietic activity.
Disciplines :
Urology & nephrology
Author, co-author :
Bovy, Christophe ; Centre Hospitalier Universitaire de Liège - CHU > Néphrologie
Gothot, André ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
Krzesinski, Jean-Marie ; Université de Liège - ULiège > Département des sciences cliniques > Néphrologie
Warling, Xavier; Centre Hospitalier Régionale de la Citadelle (Liège) - CHR CITADELLE > Néphrologie
Beguin, Yves ; Université de Liège - ULiège > Département des sciences cliniques > Hématologie - Oncologie médicale
Language :
English
Title :
Mature erythrocyte parameters as new markers of functional iron deficiency in haemodialysis: sensitivity and specificity
Evans RW, Rader B, Manninen DL. Cooperative multicenter EPO clinical trial group: The quality of life of hemodialysis recipients treated with recombinant human erythropoietin. JAMA 1990; 263: 825-830
Delano BG. Improvement in quality of life following treatment with r-HuEPO in anemic hemodialysis patients. Am J Kidney Dis 1989; 14: 14-18
Grutzmacher P, Scheuermann E, Low I et al. Correction of renal anaemia with recombinant human erythropoietin: Effects on myocardial function. Contrib Nephrol 1988; 66: 176-184
Collins AJ, Ma JZ, Ebben J. Impact of hematocrit on morbidity and mortality. Semin Nephrol 2000; 20: 345-349
Fletes R, Lazarus JM, Gage J et al. Suspected iron dextranrelated adverse drug events in hemodialysis patients. Am J Kidney Dis 2001; 37: 745-749
Ahlmén J, Vaage-Nilsen O. Safety evaluation of iron (Ferlecit®, DexFerrum®, INFeD®) from 21,060,000 doses administered I.V. in the US 1998-2000. Nephrol Dial Transplant 2002; 17[Suppl 1]: 133
Zanen AL, Adriaansen HJ, van Bommel EFH et al. Oversaturation of transferin after intravenous ferric gluconate (Ferrlecit®) in haemodialysis patients. Nephrol Dial Transplant 1996; 11: 820-824
Zager RA, Johnson ACM, Hanson Sy et al. Parenteral iron formulations: A comparative toxicologic analysis and mechanisms of cell injury. Am J Kidney Dis 2002; 40: 90-103
Tovbin D, Mazor D, Vorobiov M et al. Induction of protein oxidation by intravenous iron in hemodialysis patients: Role of inflammation. Am J Kidney Dis 2002; 40: 1005-1012
Teehan GS, Bahdouch D, Ruthazer R et al. Iron storage indices: Novel predictors of bacteremia in hemodialysis patients initiating intravenous iron therapy. Clin Infect Dis 2004; 15: 1090-1094
Canziani ME, Yumiya ST, Rangel EB et al. Risk of bacterial infection in patients under intravenous iron therapy: Dose versus length of treatment. Artif Organs 2001; 25: 866-869
Hoen B, Paul-Dauphin A, Hestin D et al. EPIBACDIAL: A multicenter prospective study of risk factors for bacteremia in chronic hemodialysis patients. J Am Soc Nephrol 1998; 8: 869-876
Tessitore N, Solero GP, Lippi G et al. The role of iron status markers in predicting response to intravenous iron in haemodialysis patients on maintenance erythropoietin. Nephrol Dial Transplant 2001; 16: 1416-1423
Bovy C, Tsobo L, Crapanzano L et al. Factors determining the percentage of hypochromic red blood cells in hemodialysis patients. Kidney Int 1999; 56: 1113-1119
Bovy C, Krzesinski JM, Gothot A et al. Impact of erythropoietic activity on red cell parameters in chronic renal failure patients. Haematologica 2004; 89: 748-749
Revised European Best Practice Guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2005; 20: 1512-3.
National Kidney Foundation DOQI, Am J Kidney Dis 1997; 30 [Suppl 3]: S218-S220.
Hörl WH, Dreyling K, Steinhauer HB et al. Iron status of dialysis patients under rhuEPO therapy. Contrib Nephrol 1990; 87: 78-86
Brugnara C, Collela GM, Cremins J et al. Effects of subcutaneous recombinant erythropoietin in normal subjects: Development of decreased reticulocyte hemoglobin content and iron-deficient erythropoiesis. J Lab Clin Med 1994; 123: 660-667
Macdougall IC, Tucker B, Thompson J et al. A randomized controlled study of iron supplementation in patients treated with erythropoietin. Kidney Int 1996; 50: 1694-1699
Fishbane S, Frei GL, Maesaka J. Reduction in recombinant human erythropoietin doses by the use of chronic intravenous iron supplementation. Am J Kidney Dis 1995; 26: 41-46
Hakim RM, Stivelman JC, Schulman G et al. Iron overload and mobilization in long-term hemodialysis patients. Am J Kidney Dis 1987; 10: 293-299
Richardson D, Bartlett C, Will EJ. Optimizing erythropoietin therapy in hemodialysis patients. Am J Kidney Dis 2001; 38: 109-117
Bovy C, Gothot A, Krzesinski JM et al. Mature erythrocyte indices: New markers of iron availability. Haematologica 2005; 90: 549-551