NDT Advance Access originally published online on November 6, 2006
Nephrology Dialysis Transplantation 2007 22(1):23-25; doi:10.1093/ndt/gfl639
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The use of IV iron in the treatment of anaemia of ESRD patients on maintenance haemodialysis: an historical and personal view
25 Le Michelangelo, 7 Avenue des Papalins, Monaco, 98000
Correspondence and offprint requests to: Stanley Shaldon, MA, MD, FRCP, 25 Le Michelangelo, 7 Avenue des Papalins, Monaco, 98000. Email: stanley.shaldon{at}libello.com
Keywords: anaemia; erythropoietin; iron; serendipity
Dr Schiesser and others have confirmed a well-reported phenomenon, that intravenous (IV) iron in apparently iron-replete patients will decrease the epoetin requirements for a given target haematocrit in patients on maintenance haemodialysis with end-stage renal disease (ESRD) [1]. The original description of a reduction in epoetin requirements by using IV iron in apparently iron-replete patients was first reported in 1993 [2] and the detailed technique of continous administration of the colloidal iron solution mixed with the heparin solution during the haemodialysis in 1997 [3].
The regular use of colloidal IV iron preparations in the treatment of the anaemia of ESRD patients on maintenance haemodialysis was first reported in 1967 [4,5]. These papers described 53 patients maintained on haemodialysis without blood transfusion. The decision to use IV iron in iron-saturated patients with biopsy-proven haemosiderosis was based upon a single patient observation and merits the use of the term serendipity. The patient was a 42-year-old Swiss alpinist who had received multiple blood transfusions for his anaemia associated with his chronic renal failure between 1962 and 1965. He was referred to the Royal Free Hospital, London with significant hepatosplenomegaly. Liver biopsy confirmed the presence of significant haemosiderosis. After 4 months of training, he was installed on a tank dialysate delivery system and Kiil dialyser in the village of Lauterbrunnen, (visited by Goethe), in the Bernese Oberland in Switzerland.
His haematocrit was 24% at the time of leaving London. On return to Switzerland it rose to 38% after several months of dialysis at 1300 m above sea level. The water used for preparation of the tank dialysate was taken straight from the drinking water tap without treatment. He began to experience fever during dialysis and culture of the water revealed a contamination with Escherichia Coli. A water softener was installed and the fevers stopped. The inlet transparent dialysate tubing which had previously been stained with iron deposits became clear and at the same time his haematocrit dropped to 24%. Following this observation, it was decided to give this patient IV iron dextran during dialysis by slow injection during the dialysis with a syringe pump and the haematocrit rose to 48%. A second patient with transfusional haemosiderosis who returned to Amman, Jordan (780 m above sea level) in 1966 had a similar experience with a rise in haematocrit to 40% with the use of IV iron. (Figure 1)
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Since that time, I have always used IV iron regularly in all patients on maintenance haemodialysis. After the beginning of the erythropoietin era, IV iron was continued and in 1993 we reported very low erythropoietin requirements in a series of patients on maintenance haemodialysis [2], and the detailed technique of using IV iron mixed with heparin in a syringe was reported in 1997 [3]. The mechanism by which the IV colloidal iron succeeded in raising the haematocrit without erythropoietin in apparently iron-overloaded patients has never been satisfactorily explained. The terms relative and absolute iron deficiency currently in use seem to be descriptive but not satisfactory. Recent evidence suggests that the blocks in iron transport associated with the old generation of ESRD patients with transfusional haemosiderosis can also be seen in the white cells of ESRD patients who have never been transfused [6]. The conclusion that can be drawn is perhaps that this is a phenomenon of uraemia possibly associated with a chronic inflammatory state [7,8]. The question of what the ideal target haematocrit should be in ESRD patients on maintenance haemodialysis is again under review, as it has been suggested that the haematocrit is not a valid surrogate for survival in patients with ESRD on maintenance haemodialysis [9,10].
The economic savings to health care authorities worldwide in respecting a haemoglobin ceiling of 11.0 g/100 ml should not be underestimated.
Conflict of interest statement. None declared.
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- Schiesser D, Binet I, Tsinalis D, et al. (2006) Weekly low-dose treatment with intravenous iron sucrose maintains iron status amd decreases eporetin requirement in iron-replete haemodialysis patients. Nephrol Dial Transplant 21:2841–2845.
[Abstract/Free Full Text] - Granolleras C, Oulès R, Branger B, Fourcade J, Shaldon S. (1993) Iron supplementation of hemodialysis patients receiving recombinant human erythropoietin therapy. In Bauer C, Koch KM, Scigalla P, Wieczorek L (Eds.). Erythropietin Molecular Physiology and Clinical Applications(Marcel Dekker, New York) pp. 211–217.
- Granolleras C, Zein A, Oulès R, Branger B, Fourcade J, Shaldon S. (1997) Continuous administration of intravenous iron during hemodialysis. Nephrol Dial Transplant 12:1007–1108.
[Abstract/Free Full Text] - Shaldon S. (1967) Chronic dialysis without transfusion. Lancet 1:783–784.
- Crockett RA, Baillod RA, Hopewell J, Shaldon S. (1967) Maintenance of 50 patients on intermittent haemodialysis without blood transfusion. Proc Eur Dial Transpl Assoc 4:17–23.[Medline]
- Otaki Y, Nakanishi T, Hasuike Y, et al. (2004) Defective regulation of iron transporters leading to excess in the polymorphonuclear leucocytes of patients on maintenance dialysis. Am J Kidney Dis 43:1030–1039.[CrossRef][Web of Science][Medline]
- Henderson LW, Koch KM, Dinarello CA, Shaldon S. (1983) Haemodialysis hypotension. The interleukin hypothesis. Blood Purification 1:3–8.[Medline]
- Shaldon S, Deschodt G, Branger B, et al. (1985) Haemodialysis hypotension: the interleukin hypothesis restated. Proc Eur Dial Transpl Assoc 22:229–243.
- Cotter DJ, Stefanik K, Zhang Y, Thamer M, Scharfstein D, Kaufman J. (2004) Hematocrit was not validated as a surrogate end point for survival among epoetin-treated hemodialysis patients. J Clin Epidemiology 57:1086–1095.[CrossRef][Web of Science][Medline]
- Cotter DJ, Tharner M, Narasimhan K, Zhang W, Bullock K. (2006) Translating epoetin research into practice: the role of government and the use of scientific evidence. Health Affairs 25:1249–1259.
[Abstract/Free Full Text]
Accepted in revised form: 5.10.06
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