Regulation of iron absorption in iron loaded subjects with end stage renal disease: effects of treatment with recombinant human erythropoietin and reduction of iron stores.

The effects on iron absorption of variation in erythroid activity, haemoglobin and iron stores were studied in six anaemic dialysis-dependent subjects in whom iron stores were increased from previous red cell transfusions. Gastrointestinal mucosal uptake and whole body retention of oral iron were measured at the beginning of the study, after starting treatment with recombinant erythropoietin (but before significant increase in haemoglobin), after partial correction of anaemia, after further reduction of iron stores by repeated phlebotomy, and when erythropoiesis decreased from the discontinuation of treatment with erythropoietin. Between successive measurements, valid comparisons were made in five subjects. Correction of anaemia decreased whole body retention of iron through decreased mucosal uptake (P = 0.032). Further reduction in iron stores through repeated phlebotomy whilst the increase in haemoglobin was maintained by treatment with erythropoietin, tended to increase whole body retention of iron through an increase in mucosal transfer (P = 0.010). With initial enhancement of erythropoiesis in anaemic iron-loaded subjects there was no change in any measured component of iron absorption. However, after correction of anaemia and reduction of iron stores, a decrease in erythropoiesis was associated with decreased whole body iron retention in all subjects through decreased mucosal transfer (P = 0.028). The data suggest that anaemia upregulates mucosal iron uptake, and that erythroid activity upregulates mucosal transfer but that this latter effect may be counter-balanced by iron overload which downregulates mucosal transfer.