MARKERS OF MASKED IRON-DEFICIENCY AND EFFECTIVENESS OF EPO THERAPY INCHRONIC-RENAL-FAILURE

Recombinant erythropoietin (rHuEPO) is well established in the managem ent of anemia of chronic renal disease. However, a number of clinical issues, including the best laboratory indicators of an imminent marrow response to rHuEPO replacement, the ideal measurements to detect mask ed iron deficiency, and optimal methods of iron replacement, remain un answered. To investigate these issues, studies were performed in anemi c chronic hemodialysis patients. A number of standard hematologic meas urements in addition to automated reticulocyte counts (Sysmex R-1000) and serum transferrin receptors (TfR) were obtained in these patients. A response to initiation of rHuEPO administration could be predicted if the serum TfR concentration was less than 6 mg/L (normal, 3.8 to 8. 5 mg/L). In patients on rHuEPO, an imminent hemoglobin response to an increased rHuEPO dose could be predicted after 1 week based on a great er than 20% increase from baseline in the serum TfR or absolute reticu locyte count, with a sensitivity of 92%. In patients on rHuEPO replace ment with serum ferritin levels greater than 30 mu g/L, none of the pa nel of tests, including serum TfR, reliably detected masked iron defic iency. In a longterm study over 5 months in patients on a stable maint enance dose of EPO, a gradual decline in total body iron occurred, eve n in subjects with initial adequate iron stores, and despite taking 50 mg elemental iron daily as oral ferrous sulphate. The serum TfR is us eful for predicting a hemoglobin response when initiating rHuEPO thera py, and combined with automated reticulocyte counting it is valuable f or predicting a hemoglobin response when increasing the dose of rHuEPO , The serum TfR loses its specificity for detecting tissue iron defici ency in patients on maintenance rHuEPO therapy because of increased er ythropoiesis, which itself raises serum TfR levels. (C) 1997 by the Na tional Kidney Foundation, Inc.