Erythropoietin resistance

Most patients with Al intoxication develop an erythropoietin-resistant microcytic anemia in the absence of iron deficiency, and this may be a useful early indication of Al toxicity [41,93,254,255]. The chemical similarity between Fe3+ and Al3+ suggest that both elements will have similar metabolic effects, suggesting that iron and Al compete during erythropoiesis, resulting from a reversible block in heme synthesis due either to a defect in porphyrin synthesis or to impaired iron utilization. It was also suggested that the main mechanisms for Al toxicity in the erythropoietic system are the interference of Al in the uptake and utilization of iron and an interaction of Al with cellular membrane components, affecting not only their structures but also their functions [256]. 

Abu-Alfa AK, et al. ACE inhibitors do not induce recombinant human erythropoietin resistance in hemodialysis patients. Am J Kidney Dis 2000 35 1076-1082. 

Silverberg DS, Wexler D, Blum M, et al. The use of subcutaneous erythropoietin and intravenous iron for the treatment of the anemia of severe, resistant congestive heart failure improves cardiac and renal function and functional cardiac class, and markedly reduces hospitalizations. J Am Coll Cardiol. Jun 2000 35(7) 1737-1744. 

Anabolic steroids are also still used in refractory anemias, although with recombinant human erythropoietin now widely available they appear to be seen mainly as a means of increasing the response to erythropoietin in highly resistant cases combination treatment with erythropoietin, a glucocorticoid, and nandrolone has also been recommended for treating myelodysplastic syndromes (13). Again, in such exceptional situations the risks of anabolic steroids have to be accepted. 

Erythropoietin [ery throw PO eetin] is a glycoprotein, normally made by the kidney, that regulates red cell proliferation and differentiation in bone marrow. Human erythropoietin, produced by recombinant DNA technology, is effective in the treatment of anemia caused by end-stage renal disease, anemia associated with HIV-infected patients, and anemia in some cancer patients. Supplementation with iron may be required to assure an adequate response. The protein is usually administered intravenously in renal dialysis patients, but in others the subcutaneous route is preferred. Side effects such as iron deficiency and an elevation in blood pressure occur. [Note The latter may be due to increases in peripheral vascular resistance and/or blood viscosity.]... 

Several factors contribute to the development of hypertension. One is the loss of the hypoxic vasodilatory response, leading to an increase in peripheral vascular resistance (63), but more important is the rise in blood viscosity, which increases with the hematocrit in both normotensive and hypertensive individuals (64). It is still being debated whether hypertension occurs only in patients with pre-existing hypertension or in normotensive patients as well, but about 30% of all patients require increased or de novo antihypertensive therapy as they respond to erythropoietin treatment (65). 

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