Epoetin Alfa Resistance: Valuation of a Management Algorithm: DISCUSSION part 2
Aluminum intoxication has been long recognized as an independent cause of a microcytic hypochromic anemia in patients with end-stage renal disease who require dialysis. Aluminum seems to interfere with heme synthesis enzymes, resulting in an accumulation of protoporphyrin and interference in iron distribution and metabolism. Not surprisingly, aluminum overload markedly reduces the response to epoetin alfa. Treatment of aluminum overload with deferoxamine has resulted in improvements in hematocrit. Aluminum intoxication is rare because most hemodialysis units deionize the dialysis water used during treatment, thereby eliminating a previously important source of aluminum. Currently, the major causes of aluminum intoxication include the use of aluminum-containing phosphate binders. For patients with identified aluminum intoxication characterized by a serum aluminum level greater than 2300 nmol/L, discontinuation of aluminum-containing phosphate binders and substitution of a calcium-containing phosphate binder such as calcium carbonate or acetate or a noncalcium- containing nonaluminum-containing phosphate binder such as sevelamer is recommended.
Several patients who were inadequately dialysed (Kt/V less than 1.4) were identified in the current study. In one study, inadequate dialysis, characterized by a urea reduction ratio of less than 65%, was associated with a poor response to epoetin alfa. Increasing the intensity of dialysis in underdialyzed patients resulted in an increase in the hematocrit. Uremic toxins are postulated to interfere with erythropoiesis, resulting in epoetin alfa resistance in underdialyzed patients with end-stage renal disease. Of 4 underdialyzed patients who were evaluable in the current study, 2 patients achieved their target hemoglobin when the intensity of dialysis was increased. female viagra online
Finally, other reported causes of epoetin alfa resistance include L-carnitine deficiency, pure red cell aplasia, vitamin deficiency, and poor absorption from the subcutaneous injection in obese patients.40-44 L-Carnitine is a natural carrier of fatty acids from the cellular cytoplasm to the mitochondrial matrix, where fatty acids undergo oxidation. Hemodialysis patients usually present with a severe carnitine deficiency resulting from inadequate intake, impaired synthesis, and loss of L-carnitine during dialysis. Supplementation with intravenous L-carnitine reduces epoetin alfa dosage by enhancing the stimulatory effects of erythropoietin on the production of erythroid precursors. At the renal clinic where the study was done, patients whose clinical symptoms were solely a result of L-carnitine deficiency were difficult to identify. Therefore, L-carnitine deficiency may be a diagnosis made after the exclusion of other possible causes of epoetin alfa resistance.
Vitamin B12 and folic acid deficiency is common among patients with chronic renal disease who do not receive vitamin supplementation. Therefore, some reports describe it as an important cause of resistance. Because all the patients in the current study received vitamin supplementation, vitamin deficiency was rarely identified as a cause of epoetin alfa resistance. Therefore, its prominence in the algorithm was minimized.
Also, during home dialysis or hemodialysis for patients who self-administer epoetin alfa, noncompliance may be a cause of nonresponse to epoetin alfa. These patients should receive education that stresses the importance of compliance. Hemodialysis unit nurses in the current study administered all epoetin alfa to patients during their treatments. Therefore, noncompliance with epoetin alfa was not identified as a cause of nonresponse. canadian pharmacy online
Finally, correction of anemia may not be a possible or suitable goal for patients who receive palliative dialysis or who are noncompliant with dialysis treatments. For this reason, the algorithm developed allows the clinician to choose not to correct the anemia.
Epoetin alfa resistance or nonresponse is a complex issue. The algorithm developed for the current study offers a practical tool for the identification and management of dialysis patients not responding to epoetin alfa. This tool allows systematic identification of epoetin alfa nonresponse and correction of underlying causes.